KR20230046319A - MARC1 발현을 억제하기 위한 RNAi 작제물 및 방법 - Google Patents

MARC1 발현을 억제하기 위한 RNAi 작제물 및 방법 Download PDF

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KR20230046319A
KR20230046319A KR1020237008366A KR20237008366A KR20230046319A KR 20230046319 A KR20230046319 A KR 20230046319A KR 1020237008366 A KR1020237008366 A KR 1020237008366A KR 20237008366 A KR20237008366 A KR 20237008366A KR 20230046319 A KR20230046319 A KR 20230046319A
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rnai construct
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저스틴 케이. 머레이
준 장
올리버 호만
제이슨 씨. 롱
브라이언 미드
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암젠 인크
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Abstract

본 발명은 MARC1 유전자의 발현을 감소시키기 위한 RNAi 작제물에 관한 것이다. 또한, 간 섬유증 및 지방간 질환, 예컨대 비알코올성 지방간 질환 및 비알코올성 지방간염의 치료 또는 예방을 위한, 이러한 RNAi 작제물의 사용 방법이 제시된다.

Description

MARC1 발현을 억제하기 위한 RNAi 작제물 및 방법
관련 출원에 대한 상호 참조
본 출원은 2020년 8월 13일에 출원된 미국 가출원 63/065,190호, 및 2021년 6월 23일에 출원된 미국 가출원 63/214,016호의 이익을 주장하며, 이들의 개시내용 전체는 본원에 참조로 포함된다.
전자로 제출된 텍스트 파일의 설명
본 출원에는 ASCII 형식으로 전자 제출되었고 그 전체가 본원에 참조로 포함되는 서열 목록이 포함된다. 2021년 8월 3일에 생성된 서열 목록의 컴퓨터 판독 가능한 형식의 사본은 A-2664-WO-PCT-ST25로 명명되며 1,064킬로바이트 크기이다.
기술분야
본 발명은 미토콘드리아 아미드옥심 환원 성분 1(mARC1) 단백질의 간 발현을 조절하기 위한 조성물 및 방법에 관한 것이다. 특히, 본 발명은 RNA 간섭을 통해 MARC1 유전자 발현을 감소시키기 위한 핵산 기반 치료제 및 순환 지질 수준을 감소시키고 지방간 질환 및 간 섬유증을 치료 또는 예방하기 위한 이러한 핵산 기반 치료제의 사용 방법에 관한 것이다.
다양한 간 병리를 포함하여, 비알코올성 지방간 질환(NAFLD)은 세계에서 가장 흔한 만성 간 질환이며, 이의 유병률은 지난 20년 동안 2배가 되었으며, 현재 세계 인구의 약 20~30%에 영향을 미치는 것으로 추정된다. 일부 개체에서, 지방증(steatosis)이라 불리는, 간에서 이소성 지방의 축적은 염증 및 간세포 손상을 유발하여, 비알코올성 지방간염(NASH)이라 불리는 보다 진행된 단계의 질환으로 이어진다. NASH는 세포 손상, 염증, 및 다양한 정도의 흉터 또는 섬유증의 증거가 있는 지질 축적으로 정의된다. 2015년 기준 7500만~1억 명의 미국인이 NAFLD가 있는 것으로 추정되는 반면, NASH는 NAFLD 진단 중 약 10~30%를 차지한다.
mARC1 단백질은 N-산소화 분자의 환원을 촉매하는 미토콘드리아 외막 내 몰리브덴 함유 단백질이다(Klein et al., J Biol Chem, Vol. 287(51):42795-42803, 2012; Ott et al., J Biol Inorg Chem, Vol. 20(2):265-275, 2015). 이는 가장 두드러진 생체 변환 효소 중 하나인 CYP450에 대한 매우 효과적인 대응물이며, 아미드옥심 전구약물의 활성화뿐만 아니라 N-하이드록실화된 작용기를 포함하는 다른 약물의 불활성화에도 관여한다(Neve et al., PLoS One, Vol. 10(9):e0138487, 2015; Ott et al., 2015, supra). 최근, MARC1 유전자의 예측 기능상실 변이체는 콜레스테롤 및 간 효소의 혈중 수준 감소, 간 지방 감소, 및 간경변으로부터의 보호와 관련이 있는 것으로 보고되었다. 문헌[Emdin et al., bioRxiv 594523; //doi.org/10.1101/594523, 2019; and Emdin et al., PLoS Genet, Vol. 16(4): e1008629, 2020] 참조. 구체적으로, mARC1 암호화 영역의 A165T 미스센스 변이체는 전 원인(all-cause) 간경화로부터의 보호, 컴퓨터 단층 촬영 영상에서 간 지방 수준 감소, 의사가 진단한 지방간 가능성 감소, 뿐만 아니라 8개 코호트에서 12,361건의 전 원인 간경변 사례 및 790,095명의 대조군을 분석한 결과 알라닌 트랜스아미나제, 알칼리성 포스파타제, 총 콜레스테롤, 및 LDL 콜레스테롤 수준의 혈중 수준 감소(문헌[Emdin et al., 2020, supra])와도 관련이 있었다. 콜레스테롤 수준, 간 효소 수준 감소 및 간경화 위험 감소와 관련된 추가 MARC1 대립 유전자(M187K 미스센스 돌연변이 및 R200Ter 절단 돌연변이)도 확인되었다(Emdin et al., 2020, supra). 이러한 데이터는 mARC1 효소의 결핍이 만성 간 질환 및 간경변을 방지함을 시사한다. 따라서, mARC1 기능을 표적화하는 치료제는 콜레스테롤 수준(예를 들어 비-HDL 콜레스테롤 또는 LDL 콜레스테롤 수준) 및 간 섬유증을 감소시키고 간 질환, 특히 NAFLD 및 NASH를 치료 또는 예방하는 새로운 접근법을 나타낸다.
본 발명은 MARC1 유전자를 표적으로 하고 간 세포에서 이의 발현을 감소시키는 RNAi 작제물의 설계 및 생성에 부분적으로 기초한다. MARC1 유전자 발현의 서열 특이적 억제는 심혈관 질환 및 지방간 질환과 같은 상승된 지질 수준 및 간 지방과 관련된 병태를 치료하거나 예방하는 데 유용하다. 따라서, 일 구현예에서, 본 발명은 센스 가닥 및 안티센스 가닥을 포함하는 RNAi 작제물을 제공하며, 안티센스 가닥은 mARC1 mRNA 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 예를 들어, 일부 구현예에서, 안티센스 가닥은 1, 2, 또는 3개 이하의 미스매치를 갖는 인간 mARC1 mRNA 서열(서열번호 1)의 영역의 적어도 15개의 연속 뉴클레오티드 서열에 실질적으로 상보적인 서열을 포함한다. 특정 구현예에서, 안티센스 가닥은 표 1 또는 표 2에 열거된 안티센스 서열로부터의 적어도 15개의 연속 뉴클레오티드를 갖는 영역을 포함한다.
일부 구현예에서, 본원에 기재된 RNAi 작제물의 센스 가닥은 안티센스 가닥의 서열에 충분히 상보적인 서열을 포함하여, 약 15 내지 약 30개 염기쌍 길이의 이중체 영역을 형성한다. 이러한 구현예 및 다른 구현예에서, 센스 및 안티센스 가닥은 각각 독립적으로 약 19 내지 약 30개 뉴클레오티드 길이이다. 일부 구현예에서, RNAi 작제물은 하나 또는 두 개의 평활 말단을 포함한다. 다른 구현예에서, RNAi 작제물은 하나 또는 두 개의 뉴클레오티드 오버행을 포함한다. 이러한 뉴클레오티드 오버행은 1 내지 6개의 짝없는 뉴클레오티드를 포함할 수 있고, 센스 가닥의 3' 말단, 안티센스 가닥의 3' 말단, 또는 센스 및 안티센스 가닥 둘 다의 3' 말단에 위치할 수 있다. 특정 구현예에서, RNAi 작제물은 센스 가닥의 3' 말단 및 안티센스 가닥의 3' 말단에 2개의 짝없는 뉴클레오티드의 오버행을 포함한다. 다른 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 말단에 2개의 짝없는 뉴클레오티드의 오버행 및 센스 가닥의 3' 말단/안티센스 가닥의 5' 말단에 평활 말단을 포함한다.
본 발명의 RNAi 작제물은 리보스 고리, 핵염기 또는 포스포디에스테르 골격에 변형을 갖는 뉴클레오티드를 포함하는 하나 이상의 변형된 뉴클레오티드를 포함할 수 있다. 일부 구현예에서, RNAi 작제물은 하나 이상의 2'-변형된 뉴클레오티드를 포함한다. 이러한 2'-변형된 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, 이환식 핵산(BNA), 데옥시리보뉴클레오티드, 또는 이들의 조합을 포함할 수 있다. 일 특정 구현예에서, RNAi 작제물은 하나 이상의 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드 또는 이들의 조합을 포함한다. 일부 구현예에서, RNAi 작제물의 센스 및 안티센스 가닥의 모든 뉴클레오티드는 변형된 뉴클레오티드이다. 무염기 뉴클레오티드는 예를 들어 센스 가닥의 3' 말단, 5' 말단, 또는 3' 말단과 5' 말단 둘 다에서의 말단 뉴클레오티드로서 본 발명의 RNAi 작제물에 혼입될 수 있다. 이러한 구현예에서, 무염기 뉴클레오티드는 반전될 수 있다(예를 들어 3'-3' 뉴클레오티드간 연결 또는 5'-5' 뉴클레오티드간 연결을 통해 인접 뉴클레오티드에 연결될 수 있음).
일부 구현예에서, RNAi 작제물은 적어도 하나의 골격 변형, 예컨대 변형된 뉴클레오티드간 또는 뉴클레오시드간 연결을 포함한다. 특정 구현예에서, 본원에 기재된 RNAi 작제물은 적어도 하나의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 특정 구현예에서, 포스포로티오에이트 뉴클레오티드간 연결은 센스 및/또는 안티센스 가닥의 3' 또는 5' 말단에 위치될 수 있다. 예를 들어, 일부 구현예에서, 안티센스 가닥은 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 이러한 일부 구현예에서, 센스 가닥은 이의 3' 말단의 말단 뉴클레오티드들 사이에 1개 또는 2개의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다.
특정 구현예에서, 본 발명의 RNAi 작제물의 안티센스 가닥 및/또는 센스 가닥은 표 1 또는 표 2에 열거된 안티센스 및 센스 서열을 포함하거나, 이들로 구성될 수 있다. 이러한 특정 구현예에서, RNAi 작제물은 표 1 내지 24 중 어느 하나에 열거된 이중체 화합물 중 어느 하나일 수 있다. 일부 구현예에서, RNAi 작제물은 D-1044, D-1061, D-1062, D-1067, D-1083, D-1090, D-1092, D-1093, D-1095, D-1138, D-1139, D-1143, D-1170, D-1177, D-1180, D-1191, D-1245, D-2000, D-2002, D-2003, D-2004, D-2011, D-2026, D-2028, D-2032, D-2033, D-2034, D-2035, D-2036, D-2042, D-2044, D-2045, D-2046, D-2050, D-2078, D-2079, D-2081, D-2182, D-2196, D-2238, D-2241, D-2243, D-2246, D-2255, D-2356, D-2258, D-2301, D-2316, D-2317, D-2329, D-2332, D-2341, D-2344, D-2357, D-2399, 또는 D-2510이다. 특정 구현예에서, RNAi 작제물은 D-2079, D-2081, D-2196, D-2238, D-2241, D-2255, D-2258, D-2317, D-2332, D-2357, 또는 D-2399이다.
일부 구현예에서, 본 발명의 RNAi 작제물은 인간 mARC1 mRNA 전사체(예를 들어 서열번호 1에 제시된 인간 mARC1 mRNA 전사체 서열)의 특정 영역을 표적화할 수 있다. 예를 들어, 특정 구현예에서, RNAi 작제물은 센스 가닥 및 안티센스 가닥을 포함하고, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1205 내지 1250 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 다른 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1209 내지 1239 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 또 다른 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1345 내지 1375 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 또 다른 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 2039 내지 2078 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 다른 특정 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 2048 내지 2074 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 임의의 상기 구현예에서, 안티센스 가닥의 서열은 안티센스 가닥의 서열 및 인간 mARC1 전사체의 특정 영역의 서열 사이에 1, 2, 또는 3개 이하의 미스매치를 갖는 인간 mARC1 전사체(서열번호 1)의 특정 영역의 적어도 15개의 연속 뉴클레오티드 서열에 실질적으로 상보적일 수 있다. 안티센스 가닥의 서열 및 표적 mARC1 mRNA 서열 사이에 미스매치가 발생하는 이러한 일부 구현예에서, 미스매치는 표적 mARC1 mRNA 서열 및 안티센스 가닥의 5' 말단으로부터 위치 6 및/또는 위치 8번의 뉴클레오티드 사이에 위치할 수 있다. 다른 구현예에서, 안티센스 가닥의 서열은 인간 mARC1 전사체(서열번호 1)의 특정 영역의 적어도 15개의 연속 뉴클레오티드의 서열에 완전히 상보적일 수 있다.
본 발명의 RNAi 작제물은 특정 조직 또는 세포, 예컨대, 간세포로의 RNAi 작제물의 전달 또는 흡수를 촉진하는 리간드를 추가로 포함할 수 있다. 특정 구현예에서, 리간드는 간세포로 RNAi 작제물을 전달하는 것을 표적화한다. 이러한 구현예 및 다른 구현예에서, 리간드는 갈락토스, 갈락토사민, 또는 N-아세틸-갈락토사민(GalNAc)을 포함할 수 있다. 특정 구현예에서, 리간드는 다가 갈락토스 또는 다가 GalNAc 모이어티, 예컨대, 3가 또는 4가 갈락토스 또는 GalNAc 모이어티를 포함한다. 리간드는 임의로 링커를 통해, RNAi 작제물의 센스 가닥의 5' 또는 3' 말단에 공유적으로 부착될 수 있다. 일부 구현예에서, RNAi 작제물은 본원에 기술된 화학식 I 내지 IX 중 어느 하나의 화학식에 따른 구조를 갖는 리간드 및 링커를 포함한다. 특정 구현예에서, RNAi 작제물은 화학식 VII에 따른 구조를 갖는 리간드 및 링커를 포함한다. 다른 구현예에서, RNAi 작제물은 화학식 IV에 따른 구조를 갖는 리간드 및 링커를 포함한다.
본 발명은 또한 본원에 기술된 임의의 RNAi 작제물 및 약제학적으로 허용가능한 담체, 부형제 또는 희석제를 포함하는 약제학적 조성물을 제공한다. 이러한 약제학적 조성물은 이를 필요로 하는 환자의 세포(예를 들어 간 세포)에서 MARC1 유전자의 발현을 감소시키는데 특히 유용하다. 본 발명의 약제학적 조성물이 투여될 수 있는 환자는 심혈관 질환, 지방간 질환, 간 섬유증, 또는 간경변으로 진단되거나 이에 걸릴 위험이 있는 환자 및 콜레스테롤(예를 들어 총 콜레스테롤, 비HDL 콜레스테롤, 또는 LDL 콜레스테롤) 혈중 수준이 상승된 환자를 포함할 수 있다. 따라서, 본 발명은, 본원에 기술된 RNAi 작제물 또는 약제학적 조성물을 투여하는 단계를 포함하는, 지방간 질환(예를 들어 NAFLD, NASH, 알코올성 지방간 질환, 또는 알코올성 지방간염), 간 섬유증, 또는 심혈관 질환의 치료, 예방, 또는 발병 위험의 감소를 필요로 하는 환자에서 이를 치료하거나, 예방하거나, 또는 이의 발병 위험을 감소시키는 방법을 포함한다. 특정 구현예에서, 본 발명은, 본원에 기술된 RNAi 작제물 또는 약제학적 조성물을 투여하는 단계를 포함하는, 콜레스테롤(예를 들어 총 콜레스테롤, 비-HDL 콜레스테롤, 또는 LDL 콜레스테롤)의 혈중 수준(혈청 또는 혈장) 감소를 필요로 하는 환자에서 이를 감소시키는 방법을 제공한다.
본원에 개시된 임의의 방법에서의 또는 본원에 개시된 임의의 방법에 따른 투여를 위한 의약의 제조를 위한 mARC1 표적 RNAi 작제물의 용도가 구체적으로 고려된다. 예를 들어, 본 발명은 지방간 질환(예를 들어 NAFLD, NASH, 알코올성 지방간 질환, 또는 알코올성 지방간염), 간 섬유증, 또는 심혈관 질환의 치료, 예방, 또는 발병 위험의 감소를 필요로 하는 환자에서 이를 위한 방법에 사용하기 위한 mARC1 표적 RNAi 작제물을 포함한다. 본 발명은 또한 콜레스테롤(예를 들어 총 콜레스테롤, 비-HDL 콜레스테롤, 또는 LDL 콜레스테롤)의 혈중 수준(혈청 또는 혈장)의 감소를 필요로 하는 환자에서 이를 위한 방법에 사용하기 위한 mARC1 표적 RNAi 작제물을 포함한다.
본 발명은 또한 지방간 질환(예를 들어 NAFLD, NASH, 알코올성 지방간 질환, 또는 알코올성 지방간염), 간 섬유증, 또는 심혈관 질환의 치료, 예방, 또는 발병 위험의 감소를 필요로 하는 환자에서 이를 위한 의약의 제조에 있어서 mARC1 표적 RNAi 작제물의 용도를 포함한다. 특정 구현예에서, 발명은 콜레스테롤(예를 들어 총 콜레스테롤, 비-HDL 콜레스테롤, 또는 LDL 콜레스테롤)의 혈중 수준(혈청 또는 혈장)의 감소를 필요로 하는 환자에서 이를 위한 의약의 제조에 있어서 mARC1 표적 RNAi 작제물의 용도를 제공한다.
도 1은 인간 MARC1 유전자의 전사체의 뉴클레오티드 서열을 나타낸 것이다(Ensembl 전사체 번호 ENST00000366910.9; 서열번호 1). 전사체 서열은 우라실 염기를 대체하는 티민 염기를 갖는 상보적 DNA(cDNA) 서열로서 나타낸 것이다.
도 2a 및 2b는 6주 동안 2주에 한 번, 완충제, mARC1 siRNA(이중체 번호 D-1000), 또는 대조군 siRNA(이중체 번호 D-1002)를 피하 주사한 ob/ob 마우스에서 mARC1 mRNA(도 2a) 및 mARC2 mRNA(도 2b)의 간 발현을 나타낸 막대 그래프이다. mRNA 수준은 6주차에 qPCR로 평가하였고 완충제만 주사한 동물의 mRNA 수준에 대하여 상대적으로 표현하였다.
도 3a 내지 3h는 6주 동안 2주에 한 번, 완충제, mARC1 siRNA(이중체 번호 D-1000), 또는 대조군 siRNA(이중체 번호 D-1002)를 피하 주사한 ob/ob 마우스에서 총 콜레스테롤(CHOL; 도 3a), LDL 콜레스테롤(LDL; 도 3b), HDL 콜레스테롤(HDL; 도 3c), 트리글리세리드(TG; 도 3d), 알라닌 아미노트랜스퍼라제(ALT; 도 3e), 아스파르테이트 아미노트랜스퍼라제(AST; 도 3f), C-반응성 단백질(CRP; 도 3g), 및 메탈로프로테이나제-1의 조직 억제제(TIMP-1; 도 3h)의 혈청 수준을 나타낸 그래프이다. 상이한 분석물의 혈청 수준은 6주 시점에서 임상 분석기를 사용하여 측정하였다. 평균값 ± 평균의 표준 오차(SEM)를 제공한다. * = p <0.05;** = p<0.01 대 완충제 대조군.
도 4a 및 4b는 6주 동안 2주에 한 번, 완충제, mARC1 siRNA(이중체 번호 D-1000), 또는 대조군 siRNA(이중체 번호 D-1002)를 피하 주사한 ob/ob 마우스에서 6주차의 트리글리세리드(간 TG; 도 4a) 또는 총 콜레스테롤(간 TC; 도 4b)의 간 수준을 나타낸 그래프이다. 평균값 ± SEM이 제공된다. *** = p<0.001 대 완충제 대조군.
도 5a 및 5b는 표준 차우 식이(차우 대조군) 또는 0.2% 콜레스테롤 식이(TD190883)의 c57BL/6 마우스에서 mARC1 mRNA(도 5a) 및 mARC2 mRNA(도 5b)의 간 발현을 나타낸 막대 그래프이다. 0.2% 콜레스테롤 식이를 적용한 마우스에게 24주 동안 2주에 한 번, 완충제(TD190883 대조군), mARC1 siRNA(이중체 번호 D-1000), 또는 대조군 siRNA(이중체 번호 D-1002)를 피하 주사하였다. mRNA 수준은 24주차에 qPCR로 평가하였고, 차우 대조군 동물의 mRNA 수준에 대하여 상대적으로 표현하였다.
도 6a 내지 6f는 표준 차우 식이(차우 대조군) 또는 0.2% 콜레스테롤 식이(TD190883)의 c57BL/6 마우스에서 아스파르테이트 아미노트랜스퍼라제(AST; 도 6a), 알라닌 아미노트랜스퍼라제(ALT; 도 6b), 총 콜레스테롤(도 6c), LDL 콜레스테롤(LDL-c; 도 6d), HDL 콜레스테롤(HDL-c; 도 6e), 및 트리글리세리드(도 6f)의 혈청 수준을 나타낸 그래프이다. 0.2% 콜레스테롤 식이를 적용한 마우스에게 24주 동안 2주에 한 번, 완충제(TD190883 대조군), mARC1 siRNA(이중체 번호 D-1000), 또는 대조군 siRNA(이중체 번호 D-1002)를 피하 주사하였다. 투약 후 지시된 시간에 임상 분석기를 사용하여 상이한 분석물의 혈청 수준을 측정하였다. 평균값 ± 평균의 표준 오차(SEM)를 제공한다. * = p <0.05;** = p<0.01, *** = p<0.001 대 TD190883 대조군.
도 7a 내지 7d는 표준 차우 식이(차우 대조군) 또는 0.2% 콜레스테롤 식이(TD190883)의 c57BL/6 마우스에서 24주차의 체중(도 7a), 간 중량(도 7b), 트리글리세리드 간 수준(도 7c), 및 총 콜레스테롤 간 수준(도 7d)을 나타낸 그래프이다. 0.2% 콜레스테롤 식이를 적용한 마우스에게 24주 동안 2주에 한 번, 완충제(TD190883 대조군), mARC1 siRNA(이중체 번호 D-1000), 또는 대조군 siRNA(이중체 번호 D-1002)를 피하 주사하였다. 평균값 ± SEM이 제공된다.
도 8a 내지 8f는 단일 3 mg/kg s.c. 용량의 GalNAc-접합된 mARC1 siRNA 분자 D-2241(도 8a 및 8b), D-2081(도 8c 및 8d) 및 D-2258(도 8e 및 8f)에 따른 시노몰구스 마카크 원숭이의 안티센스 가닥 및 센스 가닥 혈청 농도-시간 프로파일이다. 도 8a, 8c, 및 8e는 투여하고 0.083 내지 24시간 후의 농도-시간 프로파일을 나타낸 반면, 도 8b, 8d, 및 8f는 투여하고 0.083 내지 1056시간 후의 농도-시간 프로파일을 나타낸 것이다.
본 발명은 세포 또는 포유동물에서 MARC1 유전자의 발현을 조절하기 위한 조성물 및 방법에 관한 것이다. 일부 구현예에서, 본 발명의 조성물은 MARC1 유전자, 특히 인간 MARC1 유전자로부터 전사된 mRNA를 표적화하고 세포 또는 포유동물에서 mARC1 단백질의 발현을 감소시키는 RNAi 작제물을 포함한다. 이러한 RNAi 작제물은 혈청 지질 수준(예를 들어 총 콜레스테롤 및 LDL 콜레스테롤 수준)을 감소시키고, 다양한 형태의 심혈관 질환 및 지방간 질환(예컨대 NAFLD 및 NASH)을 치료 또는 예방하고, 간 섬유증 및 간경화로 진행될 위험을 감소시키는 데 유용하다.
본원에서 사용되는 바와 같이, 용어 "RNAi 작제물"은 세포 내로 도입될 때 RNA 간섭 메카니즘을 통해 표적 유전자(예를 들어 MARC1 유전자)의 발현을 하향조절할 수 있는 RNA 분자를 포함하는 작용제를 지칭한다. RNA 간섭은 핵산 분자가 표적 RNA 분자(예를 들어, 메신저 RNA 또는 mRNA 분자)의 절단 및 분해를 서열-특이적 방식으로, 예를 들어 RNA 유도된 사일런싱 복합체(RISC) 경로를 통해 유도하는 방법이다. 일부 구현예에서, RNAi 작제물은 이중체 영역을 형성하도록 하이브리드화하기 위해 서로에 대해 충분히 상보적인 연속 뉴클레오티드의 2개의 역평행 가닥을 포함하는 이중-가닥 RNA 분자를 포함한다. "하이브리드화하는" 또는 "하이브리드화"는 통상적으로 2개의 폴리뉴클레오티드의 상보적 염기들 사이의 수소 결합(예를 들어, 왓슨-크릭(Watson-Crick), 후그스틴(Hoogsteen) 또는 역 후그스틴 수소 결합)을 통해 상보적인 폴리뉴클레오티드의 짝형성(pairing)을 지칭한다. 표적 서열(예를 들어, 표적 mRNA)에 실질적으로 상보적인 서열을 갖는 영역을 포함하는 가닥은 "안티센스 가닥" 또는 "가이드 가닥"으로 지칭된다. "센스 가닥" 또는 "패신저 가닥"은 안티센스 가닥의 영역에 실질적으로 상보적인 영역을 포함하는 가닥을 지칭한다. 일부 구현예에서, 센스 가닥은 표적 서열과 실질적으로 동일한 서열을 갖는 영역을 포함할 수 있다.
이중-가닥 RNA 분자는 리보뉴클레오티드의 리보스 당, 염기 또는 백본 성분, 예컨대 본원에 기술되거나 당업계에 공지된 것에 대한 변형을 포함하는, 리보뉴클레오티드에 대한 화학적 변형을 포함할 수 있다. 이중-가닥 RNA 분자(예를 들어, siRNA, shRNA, 등)에 사용된, 임의의 상기 변형은 본 개시내용의 목적 상 용어 "이중-가닥 RNA"에 포함된다.
본원에서 사용되는 바와 같이, 제1 서열을 포함하는 폴리뉴클레오티드가 제2 서열을 포함하는 폴리뉴클레오티드에 하이브리드화되어 특정 조건, 예컨대 생리학적 조건하에 이중체 영역을 형성할 수 있는 경우, 제1 서열은 제2 서열에 대해 “상보적”이다. 다른 이러한 조건은 당업자에게 공지된 보통 또는 엄격한 하이브리드화 조건을 포함할 수 있다. 제1 서열 염기쌍을 포함하는 폴리뉴클레오티드가 임의의 미스매치 없이 하나 또는 두 뉴클레오티드 서열의 전체 길이에 걸쳐 제2 서열을 포함하는 폴리뉴클레오티드와 쌍을 이루는 경우, 제1 서열은 제2 서열에 대해 완전히 상보적인(100% 상보적인) 것으로 간주된다. 서열이 표적 서열에 대해 적어도 약 80%, 85%, 90%, 95%, 96%, 97%, 98%, 또는 99% 상보적인 경우, 서열은 표적 서열에 대해 "실질적으로 상보적”이다. 상보성 백분율은 제2 또는 표적 서열의 상응하는 위치에서 염기에 상보적인 제1 서열의 염기 수를 제1 서열의 총 길이로 나눔으로써 계산될 수 있다. 또한, 2개의 서열이 하이브리드화될 때 30개의 염기쌍 이중체 영역에 대해 5, 4, 3, 또는 2개 이하의 미스매치가 존재하면, 서열은 또 다른 서열에 실질적으로 상보적이라고 말할 수 있다. 일반적으로, 본원에 정의된 바와 같이, 임의의 뉴클레오티드 오버행이 존재하는 경우, 이러한 오버행의 서열은 두 서열 사이의 상보성 정도를 결정할 때 고려되지 않는다. 예를 들어, 하이브리드화하여 각 가닥의 3' 말단에 2개의 뉴클레오티드 오버행을 갖는 19개의 염기쌍 이중체 영역을 형성하는 21개 뉴클레오티드 길이의 센스 가닥 및 21개 뉴클레오티드 길이의 안티센스 가닥은 본원에서 사용되는 용어와 완전히 상보적인 것으로 간주된다.
일부 구현예에서, 안티센스 가닥의 영역은 표적 RNA 서열(예를 들어 mARC1 mRNA 서열)의 영역에 실질적으로 또는 완전히 상보적인 서열을 포함한다. 이러한 구현예에서, 센스 가닥은 안티센스 가닥의 서열에 완전히 상보적인 서열을 포함할 수 있다. 이러한 다른 구현예에서, 센스 가닥은 센스 및 안티센스 가닥에 의해 형성된 이중체 영역에서 예를 들어, 1, 2, 3, 4, 또는 5개의 미스매치를 갖는 안티센스 가닥의 서열에 실질적으로 상보적인 서열을 포함할 수 있다. 특정 구현예에서, 임의의 미스매치는 말단 영역내에서 (예를 들어, 가닥의 5' 및/또는 3' 말단의 6, 5, 4, 3, 또는 2개의 뉴클레오티드 내에서) 발생하는 것이 바람직하다. 일 구현예에서, 센스 및 안티센스 가닥으로부터 형성된 이중체 영역에서 임의의 미스매치는 안티센스 가닥의 5' 말단의 6, 5, 4, 3, 또는 2개의 뉴클레오티드 내에서 발생한다.
특정 구현예에서, 이중-가닥 RNA의 센스 가닥 및 안티센스 가닥은 이중체 영역을 형성하기 위해 하이브리드화되지만 그렇지 않으면 연결되지 않은 2개의 분리된 분자일 수 있다. 2개의 분리된 가닥으로부터 형성된 이러한 이중-가닥 RNA 분자는 "작은 간섭 RNA" 또는 "짧은 간섭 RNA"(siRNA)로 지칭된다. 따라서, 일부 구현예에서, 본 발명의 RNAi 작제물은 siRNA를 포함한다.
다른 구현예에서, 하이브리드화하여 이중체 영역을 형성하는 센스 가닥 및 안티센스 가닥은 단일 RNA 분자의 일부일 수 있으며, 즉 센스 및 안티센스 가닥은 단일 RNA 분자의 자기-상보성 영역의 일부이다. 이러한 경우에, 단일 RNA 분자는 이중체 영역(줄기 영역으로도 지칭됨) 및 루프 영역을 포함한다. 센스 가닥의 3' 말단은 짝없는 뉴클레오티드의 인접 서열에 의해 안티센스 가닥의 5' 말단에 연결되며, 이는 루프 영역을 형성할 것이다. 루프 영역은 전형적으로 안티센스 가닥이 센스 가닥과 염기쌍을 형성하여 이중체 또는 줄기 영역을 형성할 수 있도록 RNA 분자가 그 자체로 접히는 것을 허용하기에 충분한 길이를 갖는다. 루프 영역은 약 3 내지 약 25개, 약 5 내지 약 15개, 또는 약 8 내지 약 12개의 짝없는 뉴클레오티드를 포함할 수 있다. 적어도 부분적으로 자기-상보성 영역을 갖는 이러한 RNA 분자는 "짧은 헤어핀 RNA"(shRNAs)으로 지칭된다. 특정 구현예에서, 본 발명의 RNAi 작제물은 shRNA를 포함한다. 단일한, 적어도 부분적으로 자기-상보성 RNA 분자의 길이는 약 40개 뉴클레오티드 내지 약 100개 뉴클레오티드, 약 45개 뉴클레오티드 내지 약 85개 뉴클레오티드, 또는 약 50개 뉴클레오티드 내지 약 60개 뉴클레오티드일 수 있으며, 각각 본원에 인용된 길이를 갖는 이중체 영역 및 루프 영역을 포함한다.
일부 구현예에서, 본 발명의 RNAi 작제물은 센스 가닥 및 안티센스 가닥을 포함하며, 상기 안티센스 가닥은 mARC1 메신저 RNA(mRNA) 서열에 실질적으로 또는 완전히 상보적인 서열을 갖는 영역을 포함한다. 본원에서 사용되는 바와 같이, "mARC1 mRNA 서열"은 mARC1 단백질 변이체 또는 임의의 종(예를 들어 비-인간 영장류, 인간)으로부터의 이소형을 포함하는, mARC1 단백질을 암호화하는, 대립 유전자 변이체 및 스플라이스 변이체를 포함하는 임의의 메신저 RNA 서열을 지칭한다. MARC1 유전자(MTARC1 또는 MOSC1로도 알려짐)는 미토콘드리아 아미드옥심 환원 성분 1 효소(1 효소를 포함하는 MOCO 설퍼라제 C-말단 도메인으로도 알려짐)를 암호화한다. 인간에서, MARC1 유전자는 염색체 1의 유전자좌 1q41에서 발견된다.
mARC1 mRNA 서열은 또한, 이의 상보적 DNA(cDNA) 서열로서 발현된 전사체 서열을 포함한다. cDNA 서열은 RNA 염기(예를 들어, 구아닌, 아데닌, 우라실, 및 시토신)보다는 DNA 염기(예를 들어, 구아닌, 아데닌, 타이민, 및 시토신)로서 발현된 mRNA 전사체의 서열을 지칭한다. 따라서, 본 발명의 RNAi 작제물의 안티센스 가닥은 표적 mARC1 mRNA 서열 또는 mARC1 cDNA 서열에 실질적으로 또는 완전히 상보적인 서열을 갖는 영역을 포함할 수 있다. mARC1 mRNA 또는 cDNA 서열은 인간 서열: Ensembl 전사체 번호 ENST00000366910.9(도 1, 서열번호 1) 및 NCBI 참조 서열 NM_022746.4; 시노몰구스 원숭이 서열: NCBI 참조 서열 XR_001490722.1, XR_001490722.1, XR_001490723.1, XR_001490726.1, XR_273285.2, XM_005540901.2, XR_273286.2, XM_005540898.2, 및 XM_005540899.2; 레서스 원숭이 서열: NCBI 참조 서열 XM_015115809.2, XM_015115815.2, XM_001102192.4, 및 XM_001102284.3; 침팬지 서열: NCBI 참조 서열 XM_009441519.3, XM_001172926.4, 및 XM_009441521.3; 래트 서열: NCBI 참조 서열 XM_017598938.1; 및 마우스 서열: NCBI 참조 서열 XM_006497192.4와 같은, Ensembl Genome 또는 미국 국립 생명공학 정보 센터(NCBI) 데이터베이스의 임의의 mARC1 mRNA 또는 cDNA 서열을 포함할 수 있지만, 이에 제한되지 않는다. 특정 구현예에서, mARC1 mRNA 서열은 도 1에 제시된 인간 전사체(서열번호 1)이다.
안티센스 가닥의 영역은 mARC1 mRNA 서열의 적어도 15개의 연속 뉴클레오티드에 실질적으로 상보적이거나 완전히 상보적일 수 있다. 특정 구현예에서, 안티센스 가닥의 영역은 1, 2, 또는 3개 이하의 미스매치를 갖는 mARC1 mRNA 서열(예를 들어 인간 mARC1 mRNA 서열(서열번호 1))의 영역의 적어도 15개, 적어도 16개, 적어도 17개, 적어도 18개, 또는 적어도 19개의 연속 뉴클레오티드 서열에 실질적으로 상보적인 서열을 포함한다. 관련 구현예에서, 안티센스 가닥은 1개 이하의 미스매치를 갖는 mARC1 mRNA 서열의 영역의 적어도 15개, 적어도 16개, 적어도 17개, 적어도 18개, 또는 적어도 19개의 연속 뉴클레오티드 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 안티센스 가닥의 서열이 표적 mARC1 mRNA 서열에 완전히 상보적이지 않고 미스매치를 포함하는 구현예에서, 미스매치는 표적 mARC1 mRNA 서열 및 안티센스 가닥의 5' 말단으로부터 위치 6 및/또는 위치 8번에 있는 뉴클레오티드 사이에서 발생할 수 있다. 일부 구현예에서, 안티센스 가닥이 상보성 영역을 포함하는 mARC1 mRNA 서열의 표적 영역은 약 15 내지 약 30개의 연속 뉴클레오티드, 약 16 내지 약 28개의 연속 뉴클레오티드, 약 18 내지 약 26개의 연속 뉴클레오티드, 약 17 내지 약 24개의 연속 뉴클레오티드, 약 19 내지 약 30개의 연속 뉴클레오티드, 약 19 내지 약 25개의 연속 뉴클레오티드, 약 19 내지 약 23개의 연속 뉴클레오티드, 또는 약 19 내지 약 21개의 연속 뉴클레오티드의 범위일 수 있다. 특정 구현예에서, mARC1 mRNA 서열에 실질적으로 또는 완전히 상보적인 서열을 포함하는 안티센스 가닥의 영역은 표 1 또는 표 2에 열거된 안티센스 서열로부터의 적어도 15개의 연속 뉴클레오티드를 포함할 수 있다. 다른 구현예에서, 안티센스 가닥의 서열은 표 1 또는 표 2에 열거된 안티센스 서열로부터의 적어도 16개, 적어도 17개, 적어도 18개, 또는 적어도 19개의 연속 뉴클레오티드를 포함한다.
RNAi 작제물의 센스 가닥은 전형적으로 안티센스 가닥의 서열에 충분히 상보적인 서열을 포함하여, 2개의 가닥이 생리학적 조건 하에서 하이브리드화하여 이중체 영역을 형성한다. "이중체 영역"은 두 폴리뉴클레오티드 사이에 이중체를 생성하기 위해 왓슨-크릭(Watson-Crick) 염기쌍형성 또는 다른 수소 결합 상호작용에 의해 서로 염기쌍을 형성하는 2개의 상보적 또는 실질적으로 상보적인 폴리뉴클레오티드의 영역을 지칭한다. 예를 들어, 다이서(Dicer) 효소 및/또는 RISC 복합체를 관여시킴으로써 RNAi 작제물의 이중체 영역은 RNAi 작제물이 RNA 간섭 경로에 진입할 수 있도록 충분한 길이를 가져야 한다. 예를 들어, 일부 구현예에서, 이중체 영역은 약 15 내지 약 30개 염기쌍 길이이다. 이중체 영역에 대한 이 범위 내의 다른 길이도 또한 적합하며, 예컨대 약 15 내지 약 28개 염기쌍, 약 15 내지 약 26개 염기쌍, 약 15 내지 약 24개 염기쌍, 약 15 내지 약 22개 염기쌍, 약 17 내지 약 28개 염기쌍, 약 17 내지 약 26개 염기쌍, 약 17 내지 약 24개 염기쌍, 약 17 내지 약 23개 염기쌍, 약 17 내지 약 21개 염기쌍, 약 19 내지 약 25개 염기쌍, 약 19 내지 약 23개 염기쌍, 또는 약 19 내지 약 21개 염기쌍 길이이다. 특정 구현예에서, 이중체 영역은 약 17 내지 약 24개 염기쌍 길이이다. 다른 구현예에서, 이중체 영역은 약 19 내지 약 21개 염기쌍 길이이다. 일 구현예에서, 이중체 영역은 약 19개 염기쌍 길이이다. 다른 구현예에서, 이중체 영역은 약 21개 염기쌍 길이이다.
센스 가닥 및 안티센스 가닥이 2개의 별개의 분자(예를 들어, RNAi 작제물이 siRNA를 포함함)인 구현예의 경우, 센스 가닥 및 안티센스 가닥은 이중체 영역의 길이와 동일한 길이일 필요는 없다. 예를 들어, 하나 또는 양쪽 모두의 가닥은 이중체 영역보다 길 수 있고, 이중체 영역에 인접한 하나 이상의 짝없는 뉴클레오티드 또는 미스매치를 갖는다. 따라서, 일부 구현예에서, RNAi 작제물은 적어도 하나의 뉴클레오티드 오버행을 포함한다. 본원에서 사용되는 바와 같이, "뉴클레오티드 오버행"은 가닥의 말단에서 짝없는 뉴클레오티드 또는 이중체 영역을 넘어 연장되는 뉴클레오티드를 지칭한다. 뉴클레오티드 오버행은 전형적으로 한 가닥의 3' 말단이 다른 가닥의 5' 말단을 넘어 연장될 때 또는 한 가닥의 5' 말단이 다른 가닥의 3' 말단을 넘어 연장될 때 생성된다. 뉴클레오티드 오버행은 일반적으로 1 내지 6개 뉴클레오티드 길이, 1 내지 5개 뉴클레오티드 길이, 1 내지 4개 뉴클레오티드 길이, 1 내지 3개 뉴클레오티드 길이, 2 내지 6개 뉴클레오티드 길이, 2 내지 5개 뉴클레오티드 길이, 또는 2 내지 4개 뉴클레오티드 길이이다. 일부 구현예에서, 뉴클레오티드 오버행은 1, 2, 3, 4, 5, 또는 6개의 뉴클레오티드를 포함한다. 일 특정 구현예에서, 뉴클레오티드 오버행은 1 내지 4개의 뉴클레오티드를 포함한다. 특정 구현예에서, 뉴클레오티드 오버행은 2개의 뉴클레오티드를 포함한다. 다른 특정 구현예에서, 뉴클레오티드 오버행은 단일 뉴클레오티드를 포함한다.
오버행 내의 뉴클레오티드는 본원에 기재된 리보뉴클레오티드 또는 변형된 뉴클레오티드일 수 있다. 일부 구현예에서, 오버행의 뉴클레오티드는 2'-변형된 뉴클레오티드(예를 들어 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드), 데옥시리보뉴클레오티드, 무염기 뉴클레오티드, 반전된 뉴클레오티드(예를 들어 반전된 무염기 뉴클레오티드, 반전된 데옥시리보뉴클레오티드), 또는 이들의 조합이다. 예를 들어, 일 구현예에서, 오버행의 뉴클레오티드는 데옥시리보뉴클레오티드, 예를 들어, 데옥시티미딘이다. 다른 구현예에서, 오버행의 뉴클레오티드는 2'-O-메틸 변형된 뉴클레오티드, 2'-플루오로 변형된 뉴클레오티드, 2'-메톡시에틸 변형된 뉴클레오티드, 또는 이들의 조합이다. 다른 구현예에서, 오버행은 5'-우리딘-우리딘-3'(5'-UU-3') 디뉴클레오티드를 포함한다. 상기 구현예에서, UU 디뉴클레오티드는 리보뉴클레오티드 또는 변형된 뉴클레오티드, 예를 들어, 2'-변형된 뉴클레오티드를 포함할 수 있다. 다른 구현예에서, 오버행은 5'-데옥시티미딘-데옥시티미딘-3'(5'-dTdT-3') 디뉴클레오티드를 포함한다. 뉴클레오티드 오버행이 안티센스 가닥에 존재할 경우, 오버행의 뉴클레오티드는 표적 유전자 서열에 상보적일 수 있거나, 표적 유전자 서열과 미스매치를 형성할 수 있거나, 또는 일부 다른 서열(예를 들어, 폴리피리미딘 또는 폴리퓨린 서열, 예컨대, UU, TT, AA, GG 등)을 포함할 수 있다.
뉴클레오티드 오버행은 하나 또는 양쪽 모두의 가닥의 5' 말단 또는 3' 말단에 있을 수 있다. 예를 들어, 일 구현예에서, RNAi 작제물은 안티센스 가닥의 5' 말단 및 3' 말단에 뉴클레오티드 오버행을 포함한다. 다른 구현예에서, RNAi 작제물은 센스 가닥의 5' 말단 및 3' 말단에 뉴클레오티드 오버행을 포함한다. 일부 구현예에서, RNAi 작제물은 센스 가닥의 5' 말단 및 안티센스 가닥의 5' 말단에 뉴클레오티드 오버행을 포함한다. 다른 구현예에서, RNAi 작제물은 센스 가닥의 3' 말단 및 안티센스 가닥의 3' 말단에 뉴클레오티드 오버행을 포함한다.
RNAi 작제물은 이중-가닥 RNA 분자의 한쪽 말단에 단일 뉴클레오티드 오버행을 포함하고, 다른 쪽에 평활 말단을 포함할 수 있다. "평활 말단"은 센스 가닥 및 안티센스 가닥이 분자의 말단에서 완전히 염기쌍을 이루고 이중체 영역을 넘어 연장되는 짝없는 뉴클레오티드가 없음을 의미한다. 일부 구현예에서, RNAi 작제물은 센스 가닥의 3' 말단에 뉴클레오티드 오버행을 포함하고, 센스 가닥의 5' 말단 및 안티센스 가닥의 3' 말단에 평활 말단을 포함한다. 다른 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 말단에 뉴클레오티드 오버행을 포함하고, 안티센스 가닥의 5' 말단 및 센스 가닥의 3' 말단에 평활 말단을 포함한다. 특정 구현예에서, RNAi 작제물은 이중-가닥 RNA 분자의 양쪽 말단에 평활 말단을 포함한다. 이러한 구현예에서, 센스 가닥 및 안티센스 가닥은 길이가 동일하고, 이중체 영역은 센스 및 안티센스 가닥과 길이가 동일하다(즉, 분자는 전체 길이에 걸쳐 이중 가닥임).
본 발명의 RNAi 작제물의 센스 가닥 및 안티센스 가닥은 각각 독립적으로 약 15 내지 약 30개 뉴클레오티드 길이, 약 19 내지 약 30개 뉴클레오티드 길이, 약 18 내지 약 28개 뉴클레오티드 길이, 약 19 내지 약 27개 뉴클레오티드 길이, 약 19 내지 약 25개 뉴클레오티드 길이, 약 19 내지 약 23개 뉴클레오티드 길이, 약 19 내지 약 21개 뉴클레오티드 길이, 약 21 내지 약 25개 뉴클레오티드 길이, 또는 약 21 내지 약 23개 뉴클레오티드 길이일 수 있다. 특정 구현예에서, 센스 가닥 및 안티센스 가닥은 각각 독립적으로 약 18, 약 19, 약 20, 약 21, 약 22, 약 23, 약 24, 또는 약 25개 뉴클레오티드 길이이다. 일부 구현예에서, 센스 가닥 및 안티센스 가닥은 길이가 동일하지만, RNAi 작제물이 2개의 뉴클레오티드 오버행을 갖도록 가닥보다 짧은 이중체 영역을 형성한다. 예를 들어, 일 구현예에서, RNAi 작제물은 (i) 각각 21개 뉴클레오티드 길이인 센스 가닥 및 안티센스 가닥, (ii) 19개 염기쌍 길이인 이중체 영역, 및 (iii) 센스 가닥의 3' 말단 및 안티센스 가닥의 3' 말단 모두의 2개의 짝없는 뉴클레오티드의 뉴클레오티드 오버행을 포함한다. 다른 구현예에서, RNAi 작제물은 (i) 각각 23개 뉴클레오티드 길이인 센스 가닥 및 안티센스 가닥, (ii) 21개 염기쌍 길이인 이중체 영역, 및 (iii) 센스 가닥의 3' 말단 및 안티센스 가닥의 3' 말단 모두의 2개의 짝없는 뉴클레오티드의 뉴클레오티드 오버행을 포함한다. 다른 구현예에서, 센스 가닥 및 안티센스 가닥은 동일한 길이를 가지며, 이중-가닥 분자의 양쪽 말단에 뉴클레오티드 오버행이 없도록 전체 길이에 걸쳐 이중체 영역을 형성한다. 이러한 일 구현예에서, RNAi 작제물은 평활 말단이며(예를 들어 두 개의 평활 말단을 포함), (i) 각각 21개 뉴클레오티드 길이인, 센스 가닥 및 안티센스 가닥, 및 (ii) 21개 염기쌍 길이의 이중체 영역을 포함한다. 이러한 다른 구현예에서, RNAi 작제물은 평활 말단이며(예를 들어 두 개의 평활 말단을 포함), (i) 각각 23개 뉴클레오티드 길이인, 센스 가닥 및 안티센스 가닥, 및 (ii) 23개 염기쌍 길이의 이중체 영역을 포함한다. 이러한 또 다른 구현예에서, RNAi 작제물은 평활 말단이며(예를 들어 두 개의 평활 말단을 포함), (i) 각각 19개 뉴클레오티드 길이인, 센스 가닥 및 안티센스 가닥, 및 (ii) 19개 염기쌍 길이의 이중체 영역을 포함한다.
다른 구현예에서, 센스 가닥 또는 안티센스 가닥은 다른 가닥보다 길고, 두 가닥은 RNAi 작제물이 적어도 하나의 뉴클레오티드 오버행을 포함하도록 짧은 가닥의 길이와 동일한 길이를 갖는 이중체 영역을 형성한다. 예를 들어, 일 구현예에서, RNAi 작제물은 (i) 19개 뉴클레오티드 길이인, 센스 가닥, (ii) 21개 뉴클레오티드 길이인, 안티센스 가닥, (iii) 19개 염기쌍 길이의 이중체 영역, 및 (iv) 안티센스 가닥의 3' 말단에서 2개의 짝없는 뉴클레오티드의 뉴클레오티드 오버행을 포함한다. 다른 구현예에서, RNAi 작제물은 (i) 21개 뉴클레오티드 길이인, 센스 가닥, (ii) 23개 뉴클레오티드 길이인, 안티센스 가닥, (iii) 21개 염기쌍 길이의 이중체 영역, 및 (iv) 안티센스 가닥의 3' 말단에서 2개의 짝없는 뉴클레오티드의 뉴클레오티드 오버행을 포함한다.
본 발명의 RNAi 작제물의 안티센스 가닥은 표 1 또는 표 2에 열거된 안티센스 서열 중 어느 하나의 서열, 이들 안티센스 서열 중 임의의 것의 뉴클레오티드 1~19의 서열, 또는 이들 안티센스 서열 중 임의의 것의 뉴클레오티드 2~19의 서열을 포함하거나 이로 구성될 수 있다. 따라서, 일부 구현예에서, 안티센스 가닥은 서열번호 671~1339, 2072~2803, 2906~3061, 또는 3321~3655로부터 선택된 서열을 포함하거나 이로 구성된다. 다른 구현예에서, 안티센스 가닥은 서열번호 671~1339, 2072~2803, 2906~3061, 또는 3321~3655 중 어느 하나의 뉴클레오티드 1~19의 서열을 포함하거나 이로 구성된다. 또 다른 구현예에서, 안티센스 가닥은 서열번호 671~1339, 2072~2803, 2906~3061, 또는 3321~3655 중 어느 하나의 뉴클레오티드 2~19의 서열을 포함하거나 이로 구성된다. 특정 구현예에서, 안티센스 가닥은 서열번호 715, 서열번호 725, 서열번호 732, 서열번호 733, 서열번호 737, 서열번호 738, 서열번호 739, 서열번호 745, 서열번호 754, 서열번호 757, 서열번호 758, 서열번호 761, 서열번호 762, 서열번호 763, 서열번호 764, 서열번호 766, 서열번호 767, 서열번호 768, 서열번호 770, 서열번호 782, 서열번호 784, 서열번호 801, 서열번호 809, 서열번호 810, 서열번호 811, 서열번호 814, 서열번호 818, 서열번호 821, 서열번호 837, 서열번호 841, 서열번호 842, 서열번호 845, 서열번호 847, 서열번호 848, 서열번호 850, 서열번호 851, 서열번호 855, 서열번호 856, 서열번호 860, 서열번호 861, 서열번호 862, 서열번호 865, 서열번호 875, 서열번호 884, 서열번호 886, 서열번호 891, 서열번호 899, 서열번호 901, 서열번호 907, 서열번호 914, 서열번호 916, 서열번호 920, 서열번호 927, 서열번호 937, 서열번호 1056, 서열번호 1057, 서열번호 1058, 서열번호 1059, 서열번호 1078, 서열번호 2917, 서열번호 2919, 서열번호 2926, 서열번호 2946, 서열번호 2949, 서열번호 2951, 서열번호 2953, 및 서열번호 2956으로부터 선택된 서열을 포함하거나 이로 구성된다. 일부 구현예에서, 안티센스 가닥은 서열번호 715, 서열번호 732, 서열번호 733, 서열번호 737, 서열번호 738, 서열번호 739, 서열번호 745, 서열번호 754, 서열번호 757, 서열번호 761, 서열번호 762, 서열번호 763, 서열번호 764, 서열번호 766, 서열번호 767, 서열번호 784, 서열번호 801, 서열번호 809, 서열번호 810, 서열번호 811, 서열번호 814, 서열번호 841, 서열번호 842, 서열번호 845, 서열번호 848, 서열번호 851, 서열번호 856, 서열번호 860, 서열번호 862, 서열번호 914, 서열번호 916, 서열번호 927, 서열번호 937, 서열번호 1056, 서열번호 1057, 서열번호 1058, 서열번호 1059, 서열번호 1078, 서열번호 2917, 서열번호 2919, 서열번호 2926, 서열번호 2946, 서열번호 2949, 서열번호 2951, 서열번호 2953, 및 서열번호 2956으로부터 선택된 서열을 포함하거나 이로 구성된다. 다른 구현예에서, 안티센스 가닥은 서열번호 715, 서열번호 732, 서열번호 733, 서열번호 738, 서열번호 754, 서열번호 761, 서열번호 763, 서열번호 764, 서열번호 766, 서열번호 809, 서열번호 810, 서열번호 814, 서열번호 841, 서열번호 848, 서열번호 851, 서열번호 862, 서열번호 916, 서열번호 1057, 서열번호 1078, 서열번호 2919, 서열번호 2926, 서열번호 2946, 서열번호 2949, 서열번호 2953, 및 서열번호 2956으로부터 선택된 서열을 포함하거나 이로 구성된다.
이러한 구현예 및 다른 구현예에서, 본 발명의 RNAi 작제물의 센스 가닥은 표 1 또는 표 2에 열거된 센스 서열 중 어느 하나의 서열, 이들 센스 서열 중 임의의 것의 뉴클레오티드 1~19의 서열, 또는 이들 센스 서열 중 임의의 것의 뉴클레오티드 2~19의 서열을 포함하거나 이로 구성될 수 있다. 따라서, 일부 구현예에서, 센스 가닥은 서열번호 2~670, 1340~2071, 2804~2905, 또는 3062~3320로부터 선택된 서열을 포함하거나 이로 구성된다. 다른 구현예에서, 센스 가닥은 서열번호 2~670, 1340~2071, 2804~2905, 또는 3062~3320 중 어느 하나의 뉴클레오티드 1~19의 서열을 포함하거나 이로 구성된다. 또 다른 구현예에서, 센스 가닥은 서열번호 2~670, 1340~2071, 2804~2905, 또는 3062~3320 중 어느 하나의 뉴클레오티드 2~19의 서열을 포함하거나 이로 구성된다. 특정 구현예에서, 센스 가닥은 서열번호 46, 서열번호 56, 서열번호 63, 서열번호 64, 서열번호 68, 서열번호 69, 서열번호 70, 서열번호 76, 서열번호 85, 서열번호 88, 서열번호 89, 서열번호 92, 서열번호 93, 서열번호 94, 서열번호 95, 서열번호 97, 서열번호 98, 서열번호 99, 서열번호 101, 서열번호 113, 서열번호 115, 서열번호 132, 서열번호 140, 서열번호 141, 서열번호 142, 서열번호 145, 서열번호 149, 서열번호 152, 서열번호 168, 서열번호 172, 서열번호 173, 서열번호 176, 서열번호 178, 서열번호 179, 서열번호 181, 서열번호 182, 서열번호 186, 서열번호 187, 서열번호 191, 서열번호 192, 서열번호 193, 서열번호 196, 서열번호 206, 서열번호 215, 서열번호 217, 서열번호 222, 서열번호 230, 서열번호 232, 서열번호 238, 서열번호 245, 서열번호 247, 서열번호 251, 서열번호 258, 서열번호 268, 서열번호 387, 서열번호 388, 서열번호 389, 서열번호 390, 서열번호 391, 서열번호 392, 서열번호 409, 서열번호 2808, 및 서열번호 2820으로부터 선택된 서열을 포함하거나 이로 구성된다. 다른 특정 구현예에서, 센스 가닥은 서열번호 46, 서열번호 63, 서열번호 64, 서열번호 68, 서열번호 69, 서열번호 70, 서열번호 76, 서열번호 85, 서열번호 88, 서열번호 92, 서열번호 93, 서열번호 94, 서열번호 95, 서열번호 97, 서열번호 98, 서열번호 115, 서열번호 132, 서열번호 140, 서열번호 141, 서열번호 142, 서열번호 145, 서열번호 172, 서열번호 173, 서열번호 176, 서열번호 179, 서열번호 182, 서열번호 187, 서열번호 191, 서열번호 193, 서열번호 245, 서열번호 247, 서열번호 258, 서열번호 268, 서열번호 387, 서열번호 388, 서열번호 389, 서열번호 390, 서열번호 391, 서열번호 392, 서열번호 409, 서열번호 2808, 및 서열번호 2820으로부터 선택된 서열을 포함하거나 이로 구성된다. 또 다른 구현예에서, 센스 가닥은 서열번호 46, 서열번호 63, 서열번호 64, 서열번호 69, 서열번호 85, 서열번호 92, 서열번호 94, 서열번호 95, 서열번호 97, 서열번호 140, 서열번호 141, 서열번호 145, 서열번호 172, 서열번호 179, 서열번호 182, 서열번호 193, 서열번호 247, 서열번호 388, 서열번호 390, 서열번호 391, 서열번호 409, 서열번호 2808, 및 서열번호 2820으로부터 선택된 서열을 포함하거나 이로 구성된다.
본 발명의 특정 구현예에서, RNAi 작제물은 (i) 2~670, 1340~2071, 2804~2905, 또는 3062~3320으로부터 선택된 서열을 포함하거나 이로 구성된 센스 가닥 및 (ii) 서열번호 671~1339, 2072~2803, 2906~3061, 또는 3321~3655로부터 선택된 서열을 포함하거나 이로 구성된 안티센스 가닥을 포함한다. 일부 구현예에서, RNAi 작제물은 (i) 서열번호 46, 서열번호 56, 서열번호 63, 서열번호 64, 서열번호 68, 서열번호 69, 서열번호 70, 서열번호 76, 서열번호 85, 서열번호 88, 서열번호 89, 서열번호 92, 서열번호 93, 서열번호 94, 서열번호 95, 서열번호 97, 서열번호 98, 서열번호 99, 서열번호 101, 서열번호 113, 서열번호 115, 서열번호 132, 서열번호 140, 서열번호 141, 서열번호 142, 서열번호 145, 서열번호 149, 서열번호 152, 서열번호 168, 서열번호 172, 서열번호 173, 서열번호 176, 서열번호 178, 서열번호 179, 서열번호 181, 서열번호 182, 서열번호 186, 서열번호 187, 서열번호 191, 서열번호 192, 서열번호 193, 서열번호 196, 서열번호 206, 서열번호 215, 서열번호 217, 서열번호 222, 서열번호 230, 서열번호 232, 서열번호 238, 서열번호 245, 서열번호 247, 서열번호 251, 서열번호 258, 서열번호 268, 서열번호 387, 서열번호 388, 서열번호 389, 서열번호 390, 서열번호 391, 서열번호 392, 서열번호 409, 서열번호 2808, 및 서열번호 2820으로부터 선택된 서열을 포함하거나 이로 구성된 센스 가닥, 및 (ii) 서열번호 715, 서열번호 725, 서열번호 732, 서열번호 733, 서열번호 737, 서열번호 738, 서열번호 739, 서열번호 745, 서열번호 754, 서열번호 757, 서열번호 758, 서열번호 761, 서열번호 762, 서열번호 763, 서열번호 764, 서열번호 766, 서열번호 767, 서열번호 768, 서열번호 770, 서열번호 782, 서열번호 784, 서열번호 801, 서열번호 809, 서열번호 810, 서열번호 811, 서열번호 814, 서열번호 818, 서열번호 821, 서열번호 837, 서열번호 841, 서열번호 842, 서열번호 845, 서열번호 847, 서열번호 848, 서열번호 850, 서열번호 851, 서열번호 855, 서열번호 856, 서열번호 860, 서열번호 861, 서열번호 862, 서열번호 865, 서열번호 875, 서열번호 884, 서열번호 886, 서열번호 891, 서열번호 899, 서열번호 901, 서열번호 907, 서열번호 914, 서열번호 916, 서열번호 920, 서열번호 927, 서열번호 937, 서열번호 1056, 서열번호 1057, 서열번호 1058, 서열번호 1059, 서열번호 1078, 서열번호 2917, 서열번호 2919, 서열번호 2926, 서열번호 2946, 서열번호 2949, 서열번호 2951, 서열번호 2953, 및 서열번호 2956으로부터 선택된 서열을 포함하거나 이로 구성된 안티센스 가닥을 포함한다. 다른 구현예에서, RNAi 작제물은 (i) 서열번호 46, 서열번호 63, 서열번호 64, 서열번호 68, 서열번호 69, 서열번호 70, 서열번호 76, 서열번호 85, 서열번호 88, 서열번호 92, 서열번호 93, 서열번호 94, 서열번호 95, 서열번호 97, 서열번호 98, 서열번호 115, 서열번호 132, 서열번호 140, 서열번호 141, 서열번호 142, 서열번호 145, 서열번호 172, 서열번호 173, 서열번호 176, 서열번호 179, 서열번호 182, 서열번호 187, 서열번호 191, 서열번호 193, 서열번호 245, 서열번호 247, 서열번호 258, 서열번호 268, 서열번호 387, 서열번호 388, 서열번호 389, 서열번호 390, 서열번호 391, 서열번호 392, 서열번호 409, 서열번호 2808, 및 서열번호 2820으로부터 선택된 서열을 포함하거나 이로 구성된 센스 가닥, 및 (ii) 서열번호 715, 서열번호 732, 서열번호 733, 서열번호 737, 서열번호 738, 서열번호 739, 서열번호 745, 서열번호 754, 서열번호 757, 서열번호 761, 서열번호 762, 서열번호 763, 서열번호 764, 서열번호 766, 서열번호 767, 서열번호 784, 서열번호 801, 서열번호 809, 서열번호 810, 서열번호 811, 서열번호 814, 서열번호 841, 서열번호 842, 서열번호 845, 서열번호 848, 서열번호 851, 서열번호 856, 서열번호 860, 서열번호 862, 서열번호 914, 서열번호 916, 서열번호 927, 서열번호 937, 서열번호 1056, 서열번호 1057, 서열번호 1058, 서열번호 1059, 서열번호 1078, 서열번호 2917, 서열번호 2919, 서열번호 2926, 서열번호 2946, 서열번호 2949, 서열번호 2951, 서열번호 2953, 및 서열번호 2956으로부터 선택된 서열을 포함하거나 이로 구성된 안티센스 가닥을 포함한다. 또 다른 구현예에서, RNAi 작제물은 (i) 서열번호 46, 서열번호 63, 서열번호 64, 서열번호 69, 서열번호 85, 서열번호 92, 서열번호 94, 서열번호 95, 서열번호 97, 서열번호 140, 서열번호 141, 서열번호 145, 서열번호 172, 서열번호 179, 서열번호 182, 서열번호 193, 서열번호 247, 서열번호 388, 서열번호 390, 서열번호 391, 서열번호 409, 서열번호 2808, 및 서열번호 2820으로부터 선택된 서열을 포함하거나 이로 구성된 센스 가닥, 및 (ii) 서열번호 715, 서열번호 732, 서열번호 733, 서열번호 738, 서열번호 754, 서열번호 761, 서열번호 763, 서열번호 764, 서열번호 766, 서열번호 809, 서열번호 810, 서열번호 814, 서열번호 841, 서열번호 848, 서열번호 851, 서열번호 862, 서열번호 916, 서열번호 1057, 서열번호 1078, 서열번호 2919, 서열번호 2926, 서열번호 2946, 서열번호 2949, 서열번호 2953, 및 서열번호 2956으로부터 선택된 서열을 포함하거나 이로 구성된 안티센스 가닥을 포함한다.
특정 구현예에서, 본 발명의 RNAi 작제물은 하기를 포함한다: (i) 서열번호 46의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 715의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (ii) 서열번호 63의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 732의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (iii) 서열번호 64의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 733의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (iv) 서열번호 69의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 738의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (v) 서열번호 85의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 754의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (vi) 서열번호 92의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 761의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (vii) 서열번호 94의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 763의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (viii) 서열번호 95의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 764의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (ix) 서열번호 97의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 766의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (x) 서열번호 140의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 809의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xi) 서열번호 141의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 810의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xii) 서열번호 145의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 814의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xiii) 서열번호 172의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 841의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xiv) 서열번호 179의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 848의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xv) 서열번호 182의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 851의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xvi) 서열번호 193의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 862의 서열을 포함하거나 이로 구성되는 안티센스 가닥; 또는 (xvii) 서열번호 247의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 916의 서열을 포함하거나 이로 구성되는 안티센스 가닥.
다른 특정 구현예에서, 본 발명의 RNAi 작제물은 하기를 포함한다: (i) 서열번호 409의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 1078의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (ii) 서열번호 388의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 1057의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (iii) 서열번호 2808의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2926의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (iv) 서열번호 2820의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2946의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (v) 서열번호 391의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2949의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (vi) 서열번호 390의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2956의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (vii) 서열번호 179의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2919의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (viii) 서열번호 388의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2953의 서열을 포함하거나 이로 구성되는 안티센스 가닥; 또는 (ix) 서열번호 388의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 1057의 서열을 포함하거나 이로 구성되는 안티센스 가닥.
일부 구현예에서, 본 발명의 RNAi 작제물은 하기를 포함한다: (i) 서열번호 2009에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2741에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (ii) 서열번호 2011에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2743에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (iii) 서열번호 2012에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2744에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (iv) 서열번호 2013에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2745에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (v) 서열번호 2020에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2752에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (vi) 서열번호 2035에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2767에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (vii) 서열번호 2037에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2769에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (viii) 서열번호 2041에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2773에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (ix) 서열번호 2042에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2774에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (x) 서열번호 2043에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2775에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xi) 서열번호 2044에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2776에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xii) 서열번호 2045에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2777에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xiii) 서열번호 2051에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2783에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xiv) 서열번호 2053에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2785에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xv) 서열번호 2054에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2786에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (xvi) 서열번호 2055에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2787에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; 또는 (xvii) 서열번호 2059에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 2791에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥.
다른 구현예에서, 본 발명의 RNAi 작제물은 하기를 포함한다: (i) 서열번호 3078에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3337에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (ii) 서열번호 3080에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3339에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (iii) 서열번호 3163에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3441에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (iv) 서열번호 3183에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3469에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (v) 서열번호 3076에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3472에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (vi) 서열번호 3077에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3484에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (vii) 서열번호 2051에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3545에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (viii) 서열번호 3080에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3481에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (ix) 서열번호 3188에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3339에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; (x) 서열번호 3080에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3476에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥; 또는 (xi) 서열번호 3223에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 센스 가닥 및 서열번호 3517에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는 안티센스 가닥.
본 발명의 RNAi 작제물은 표 1 내지 24(화합물의 변형되지 않은 뉴클레오티드 서열 및/또는 변형된 뉴클레오티드 서열 포함)에 열거된 이중체 화합물 중 임의의 것일 수 있다. 일부 구현예에서, RNAi 작제물은 표 1에 열거된 이중체 화합물 중 임의의 것이다. 다른 구현예에서, RNAi 작제물은 표 2(화합물의 변형되지 않은 뉴클레오티드 서열 및/또는 변형된 뉴클레오티드 서열 포함)에 열거된 이중체 화합물 중 임의의 것이다. 특정 구현예에서, RNAi 작제물은 D-1044, D-1061, D-1062, D-1067, D-1083, D-1090, D-1092, D-1093, D-1095, D-1138, D-1139, D-1143, D-1170, D-1177, D-1180, D-1191, D-1245, D-2000, D-2002, D-2003, D-2004, D-2011, D-2026, D-2028, D-2032, D-2033, D-2034, D-2035, D-2036, D-2042, D-2044, D-2045, D-2046, D-2050, D-2078, D-2079, D-2081, D-2182, D-2196, D-2238, D-2241, D-2243, D-2246, D-2255, D-2258, D-2301, D-2316, D-2317, D-2329, D-2332, D-2341, D-2344, D-2356, D-2357, D-2399, 또는 D-2510이다. 다른 특정 구현예에서, RNAi 작제물은 D-2079, D-2081, D-2196, D-2238, D-2241, D-2255, D-2258, D-2317, D-2332, D-2357, 또는 D-2399이다.
특정 구현예에서, 본 발명의 RNAi 작제물은 인간 mARC1 전사체 서열의 특정 영역을 표적화할 수 있다. 실시예 4에 기술되고 표 23에 요약된 바와 같이, 인간 mARC1 전사체(서열번호 1)의 특정 영역에 상보적인 서열을 갖도록 설계된 안티센스 가닥을 갖는 특정 RNAi 작제물은 전사체의 다른 영역에 상보적인 안티센스 가닥을 갖는 RNAi 작제물과 비교하여 더 우수한 인간 mARC1 mRNA의 생체내 녹다운 활성을 보이는 것으로 밝혀졌다. 따라서, 본 발명의 일부 구현예에서, 세포에서 인간 MARC1 유전자의 발현을 억제하는 데 특히 적합한 RNAi 작제물은, 하이브리드화하여 약 15 내지 약 30개 염기쌍 길이의 이중체 영역을 형성하는 센스 가닥 및 안티센스 가닥을 포함하고, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1205 내지 1250 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 일 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1209 내지 1239 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 다른 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1211 내지 1236 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 이러한 일부 구현예에서, 안티센스 가닥은 1, 2, 또는 3개 이하의 미스매치를 갖는, 서열번호 1의 뉴클레오티드 1205 내지 1250, 뉴클레오티드 1209 내지 1239, 또는 뉴클레오티드 1211 내지 1236 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는다. 다른 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1205 내지 1250, 뉴클레오티드 1209 내지 1239, 또는 뉴클레오티드 1211 내지 1236 중 적어도 15개의 연속 뉴클레오티드의 서열에 완전히 상보적인 서열을 갖는다. 인간 mARC1 전사체의 뉴클레오티드 1205 내지 1250을 표적화하는 RNAi 작제물은 D-2063, D-2066, D-2076, D-2077, D-2078, D-2080, D-2081, D-2108, D-2113, D-2142, D-2240, D-2241, D-2243, D-2245, D-2246, D-2248, D-2250, D-2251, D-2253, D-2255, D-2256, D-2258, D-2259, D-2261, D-2264, D-2265, D-2268, D-2269, D-2270, D-2271, D-2301, D-2309, D-2311, D-2312, D-2314, D-2316, D-2317, D-2319, D-2321, D-2322, D-2324, D-2326, D-2327, D-2329, D-2331, D-2332, D-2334, D-2336, D-2337, D-2339, D-2341, D-2342, D-2344, D-2346, D-2347, D-2349, D-2351, D-2352, D-2354, D-2356, D-2357, D-2376, D-2380, D-2393, D-2395, D-2396, D-2431, D-2436, D-2437, D-2440, D-2441, D-2444, D-2445, D-2447, D-2453, D-2518, D-2519, D-2520, D-2521, D-2522, D-2523, D-2524, D-2525, D-2526, D-2527, D-2528, D-2529, D-2530, D-2531, D-2532, D-2533, D-2534, 및 D-2535를 포함하지만, 이에 제한되지 않는다. 일부 구현예에서, 인간 mARC1 전사체의 뉴클레오티드 1205 내지 1250을 표적화하는 RNAi 작제물은 D-2063, D-2066, D-2076, D-2077, D-2078, D-2080, D-2081, D-2108, D-2113, D-2142, 또는 D-2301이다. 특정 구현예에서, 서열번호 1의 뉴클레오티드 1205 내지 1250, 특히 뉴클레오티드 1211 내지 1236을 표적화하는 RNAi 작제물은 5'-CAUCUAAUAUUCCAG-3'(서열번호 3656)의 서열을 포함하는 안티센스 가닥을 포함한다.
다른 구현예에서, 본 발명의 RNAi 작제물은, 하이브리드화하여 약 15 내지 약 30개 염기쌍 길이의 이중체 영역을 형성하는 센스 가닥 및 안티센스 가닥을 포함하고, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1345 내지 1375 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 일 구현예에서, 안티센스 가닥은 1, 2, 또는 3개 이하의 미스매치를 갖는, 서열번호 1의 뉴클레오티드 1345 내지 1375 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 포함한다. 다른 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1345 내지 1375 중 적어도 15개의 연속 뉴클레오티드의 서열에 완전히 상보적인 서열을 포함한다. 인간 mARC1 전사체의 뉴클레오티드 1345 내지 1375를 표적화하는 예시적인 RNAi 작제물은 D-2042, D-2043, D-2047, D-2052, D-2158, D-2162, D-2169, D-2182, D-2183, D-2184, D-2185, D-2186, D-2187, D-2189, D-2211, D-2213, D-2304, D-2305, D-2306, D-2307, D-2308, D-2384, D-2384, D-2385, D-2386, D-2387, D-2388, D-2389, D-2390, D-2391, D-2392, D-2399, D-2400, D-2401, D-2402, D-2403, D-2488, D-2494, D-2500, D-2506, D-2512, D-2538, D-2539, D-2540, 및 D-2541을 포함하지만, 이에 제한되지 않는다. 일부 구현예에서, 인간 mARC1 전사체의 뉴클레오티드 1345 내지 1375을 표적화하는 RNAi 작제물은 D-2042, D-2043, D-2047, D-2052, D-2304, D-2305, D-2306, D-2307, 또는 D-2308이다. 특정 구현예에서, 서열번호 1의 뉴클레오티드 1345 내지 1375, 특히 뉴클레오티드 1350 내지 1375을 표적화하는 RNAi 작제물은 5'-UGGGACAUUGAAGCA-3'(서열번호 3657)의 서열을 포함하는 안티센스 가닥을 포함한다.
또 다른 구현예에서, 본 발명의 RNAi 작제물은, 하이브리드화하여 약 15 내지 약 30개 염기쌍 길이의 이중체 영역을 형성하는 센스 가닥 및 안티센스 가닥을 포함하고, 안티센스 가닥은 서열번호 1의 뉴클레오티드 2039 내지 2078 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 일 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 2048 내지 2074 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함한다. 이러한 일부 구현예에서, 안티센스 가닥은 1, 2, 또는 3개 이하의 미스매치를 갖는, 서열번호 1의 뉴클레오티드 2039 내지 2078 또는 뉴클레오티드 2048 내지 2074 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는다. 다른 구현예에서, 안티센스 가닥은 서열번호 1의 뉴클레오티드 2039 내지 2078 또는 뉴클레오티드 2048 내지 2074 중 적어도 15개의 연속 뉴클레오티드의 서열에 완전히 상보적인 서열을 갖는다. 인간 mARC1 전사체의 뉴클레오티드 2039 내지 2078을 표적화하는 RNAi 작제물은 D-2045, D-2065, D-2079, D-2082, D-2105, D-2106, D-2137, D-2143, D-2166, D-2173, D-2193, D-2242, D-2247, D-2252, D-2257, D-2260, D-2262, D-2266, D-2272, D-2273, D-2302, D-2303, D-2310, D-2313, D-2315, D-2318, D-2320, D-2323, D-2325, D-2328, D-2330, D-2333, D-2335, D-2338, D-2340, D-2343, D-2345, D-2348, D-2350, D-2353, D-2355, D-2358, D-2394, D-2397, D-2454, D-2455, D-2456, D-2457, D-2458, D-2459, D-2460, D-2463, D-2465, D-2465, D-2468, D-2470, D-2472, D-2473, D-2477, D-2487, D-2493, D-2499, D-2505, D-2511, D-2552, D-2553, D-2554, D-2555, D-2556, 및 D-2557을 포함하지만, 이에 제한되지 않는다. 특정 구현예에서, 인간 mARC1 전사체의 뉴클레오티드 2039 내지 2078을 표적화하는 RNAi 작제물은 D-2045, D-2065, D-2079, D-2082, D-2105, D-2106, D-2137, D-2143, D-2302, 또는 D-2303이다. 다른 특정 구현예에서, 서열번호 1의 뉴클레오티드 2039 내지 2078, 특히 뉴클레오티드 2048 내지 2074을 표적화하는 RNAi 작제물은 5'-AUCAGAUCUUAGAGU-3'(서열번호 3658)의 서열을 포함하는 안티센스 가닥을 포함한다.
본 발명의 RNAi 작제물은 하나 이상의 변형된 뉴클레오티드를 포함할 수 있다. "변형된 뉴클레오티드"는 뉴클레오시드, 핵염기, 펜토스 고리, 또는 포스페이트 기에 하나 이상의 화학적 변형을 갖는 뉴클레오티드를 지칭한다. 본원에서 사용되는 바와 같이, 변형된 뉴클레오티드는 아데노신 모노포스페이트, 구아노신 모노포스페이트, 우리딘 모노포스페이트, 및 시티딘 모노포스페이트를 함유하는 리보뉴클레오티드를 포함하지 않는다. 그러나 RNAi 작제물은 변형된 뉴클레오티드 및 리보뉴클레오티드의 조합을 포함할 수 있다. 변형된 뉴클레오티드를 이중-가닥 RNA 분자의 하나 또는 양쪽 가닥에 통합하면, 예를 들어, 뉴클레아제 및 다른 분해 과정에 대한 분자의 감수성을 감소시킴으로써 RNA 분자의 생체내 안정성을 향상시킬 수 있다. 표적 유전자의 발현을 감소시키기 위한 RNAi 작제물의 효능은 또한 변형된 뉴클레오티드의 혼입에 의해 향상될 수 있다.
특정 구현예에서, 변형된 뉴클레오티드는 리보스 당의 변형을 갖는다. 이러한 당 변형은 펜토스 고리의 2' 및/또는 5' 위치에서의 변형뿐만 아니라 이환식 당 변형을 포함할 수 있다. 2'-변형된 뉴클레오티드는 OH 이외의 2' 위치에 치환기를 갖는 펜토스 고리를 갖는 뉴클레오티드를 지칭한다. 이러한 2'-변형은 2'-H(예를 들어 데옥시리보뉴클레오티드), 2'-O-알킬(예를 들어 -O-C1-C10 또는 -O-C1-C10 치환된 알킬), 2'-O-알릴(-O-CH2CH=CH2), 2'-C-알릴, 2'-데옥시-2'-플루오로(또한 2'-F 또는 2'-플루오로로 지칭됨), 2'-O-메틸(-OCH3), 2'-O-메톡시에틸(-O-(CH2)2OCH3), 2'-OCF3, 2'-O(CH2)2SCH3, 2'-O-아미노알킬, 2'-아미노(예를 들어 NH2), 2'-O-에틸아민, 및 2'-아지도를 포함하지만, 이에 제한되지 않는다. 펜토스 고리의 5' 위치에서의 변형은 5'-메틸 (R 또는 S 배열); 5'-비닐, 및 5'-메톡시를 포함하지만, 이에 제한되지 않는다.
"이환식 당 변형"은 브릿지가 고리의 두 원자를 연결하여 제2 고리를 형성하여 이환식 당 구조를 생성하는 펜토스 고리의 변형을 지칭한다. 일부 구현예에서, 이환식 당 변형은 펜토스 고리의 4' 및 2' 탄소 사이의 브릿지를 포함한다. 이환식 당 변형을 갖는 당 모이어티를 포함하는 뉴클레오티드는 본원에서 이환식 핵산 또는 BNA로 지칭된다. 예시적인 이환식 당 변형은 α-L-메틸렌옥시(4'-CH2-O-2') 이환식 핵산(BNA); β-D-메틸렌옥시(4'-CH2-O-2') BNA(잠금 핵산(locked nucleic acid) 또는 LNA로도 지칭됨); 에틸렌옥시(4'-(CH2)2-O-2') BNA; 아미노옥시(4'-CH2-O-N(R)-2', R은 H, C1-C12 알킬, 또는 보호기임) BNA; 옥시아미노(4'-CH2-N(R)-O-2', R은 H, C1-C12 알킬, 또는 보호기임) BNA; 메틸(메틸렌옥시)(4'-CH(CH3)-O-2') BNA(구속된 에틸(constrained ethyl) 또는 cEt로도 지칭됨); 메틸렌-티오(4'-CH2-S-2') BNA; 메틸렌-아미노(4'-CH2-N(R)-2', R은 H, C1-C12 알킬, 또는 보호기임) BNA; 메틸 탄소환식(4'-CH2-CH(CH3)-2') BNA; 프로필렌 탄소환식(4'-(CH2)3-2') BNA; 및 메톡시(에틸렌옥시)(4'-CH(CH2OMe)-O-2') BNA(구속된 MOE 또는 cMOE로도 지칭됨)를 포함하지만, 이에 제한되지 않는다. 본 발명의 RNAi 작제물에 포함될 수 있는 이들 및 다른 당-변형된 뉴클레오티드는 미국 특허 제9,181,551호, 미국 특허 공개 번호 2016/0122761, 및 Deleavey and Damha, Chemistry and Biology, Vol. 19: 937-954, 2012에 기재되어 있으며, 이들은 그 전문이 본원에 참고로 포함된다.
일부 구현예에서, RNAi 작제물은 하나 이상의 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, 이환식 핵산(BNA), 데옥시리보뉴클레오티드, 또는 이들의 조합을 포함한다. 특정 구현예에서, RNAi 작제물은 하나 이상의 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 또는 이들의 조합을 포함한다. 일 특정 구현예에서, RNAi 작제물은 하나 이상의 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드 또는 이들의 조합을 포함한다.
RNAi 작제물의 센스 및 안티센스 가닥 둘 다는 1개 또는 다수의 변형된 뉴클레오티드를 포함할 수 있다. 예를 들어, 일부 구현예에서, 센스 가닥은 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 또는 그 이상의 변형된 뉴클레오티드를 포함한다. 특정 구현예에서, 센스 가닥내 모든 뉴클레오티드는 변형된 뉴클레오티드이다. 일부 구현예에서, 안티센스 가닥은 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 또는 그 이상의 변형된 뉴클레오티드를 포함한다. 다른 구현예에서, 안티센스 가닥내 모든 뉴클레오티드는 변형된 뉴클레오티드이다. 다른 특정 구현예에서, 센스 가닥내 모든 뉴클레오티드 및 안티센스 가닥내 모든 뉴클레오티드는 변형된 뉴클레오티드이다. 이러한 구현예 및 다른 구현예에서, 변형된 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 또는 이들의 조합일 수 있다.
특정 구현예에서, 본 발명의 RNAi 작제물의 가닥 중 하나 또는 둘 모두에 혼입된 변형된 뉴클레오티드는 핵염기(본원에서 "염기"로도 지칭됨)의 변형을 갖는다. "변형된 핵염기" 또는 "변형된 염기"는 자연 발생 퓨린 염기 아데닌 (A) 및 구아닌 (G) 및 피리미딘 염기 타이민 (T), 시토신 (C), 및 우라실 (U) 이외의 염기를 지칭한다. 변형된 핵염기는 합성 및 천연 변형일 수 있고, 유니버셜 염기, 5-메틸시토신(5-me-C), 5-하이드록시메틸 시토신, 잔틴(X), 하이포잔틴(I), 2-아미노아데닌, 6-메틸아데닌, 6-메틸구아닌, 및 아데닌 및 구아닌의 다른 알킬 유도체, 아데닌 및 구아닌의 2-프로필 및 다른 알킬 유도체, 2-티오우라실, 2-티오타이민 및 2-티오시토신, 5-할로우라실 및 시토신, 5-프로피닐 우라실 및 시토신, 6-아조 우라실, 시토신 및 타이민, 5-우라실(슈도우라실), 4-티오우라실, 8-할로, 8-아미노, 8-티올, 8-티오알킬, 8-하이드록실 및 다른 8-치환된 아데닌 및 구아닌, 5-할로, 특히 5-브로모, 5-트라이플루오로메틸 및 다른 5-치환된 우라실 및 시토신, 7-메틸구아닌 및 7-메틸아데닌, 8-아자구아닌 및 8-아자아데닌, 7-데아자구아닌 및 7-데아자아데닌 및 3-데아자구아닌 및 3-데아자아데닌을 포함하지만, 이에 제한되지 않는다.
일부 구현예에서, 변형된 염기는 유니버셜 염기이다. "유니버셜 염기"는 이중체 영역의 이중 나선 구조를 변경하지 않고 RNA 및 DNA에서 모든 천연 염기와 염기쌍을 무차별적으로 형성하는 염기 유사체를 지칭한다. 유니버셜 염기는 당업자에게 공지되어 있으며, 이노신, C-페닐, C-나프틸 및 다른 방향족 유도체, 아졸 카르복사미드, 및 니트로아졸 유도체, 예컨대 3-니트로피롤, 4-니트로인돌, 5-니트로인돌, 및 6-니트로인돌을 포함하지만, 이에 제한되지 않는다.
본 발명의 RNAi 작제물에 포함될 수 있는 다른 적합한 변형된 염기는 Herdewijn, Antisense Nucleic Acid Drug Dev., Vol. 10: 297-310, 2000 및 Peacock et al., J. Org. Chem., Vol. 76: 7295-7300, 2011에 기재된 것들을 포함하며, 이들은 둘 다 그 전문이 본원에 참조로 포함된다. 당업자는 구아닌, 시토신, 아데닌, 타이민, 및 우라실이 이러한 대체 핵 염기를 보유하는 뉴클레오티드를 포함하는 폴리뉴클레오티드의 염기쌍 특성을 실질적으로 변경시키지 않으면서 다른 핵염기, 예컨대 상기 기재된 변형된 핵염기에 의해 대체될 수 있음을 잘 알고 있다.
일부 구현예에서, RNAi 작제물의 센스 및 안티센스 가닥은 1개 이상의 무염기 뉴클레오티드를 포함할 수 있다. “무염기 뉴클레오티드” 또는 “무염기 뉴클레오시드”는 리보스 당의 1' 위치에 핵염기가 결여된 뉴클레오티드 또는 뉴클레오시드이다. 특정 구현예에서, 무염기 뉴클레오티드는 RNAi 작제물의 센스 및/또는 안티센스 가닥의 말단으로 혼입된다. 일 구현예에서, 센스 가닥은 이의 3' 말단, 이의 5' 말단, 또는 이의 3' 및 5' 말단 둘 다에서 말단 뉴클레오티드로서 무염기 뉴클레오티드를 포함한다. 다른 구현예에서, 안티센스 가닥은 이의 3' 말단, 이의 5' 말단, 또는 이의 3' 및 5' 말단 둘 다에서 말단 뉴클레오티드로서 무염기 뉴클레오티드를 포함한다. 무염기 뉴클레오티드가 말단 뉴클레오티드인 이러한 구현예에서, 이는 반전된 뉴클레오티드일 수 있다 - 즉, 천연의 3'-5' 뉴클레오티드간 연결 대신 3'-3' 뉴클레오티드간 연결(가닥의 3' 말단에 있을 때)을 통해 또는 5'-5' 뉴클레오티드간 연결(가닥의 5' 말단에 있을 때)을 통해 인접 뉴클레오티드에 연결될 수 있다. 또한, 무염기 뉴클레오티드는 당 변형, 예컨대, 전술한 임의의 당 변형을 포함할 수 있다. 특정 구현예에서, 무염기 뉴클레오티드는 2'-변형, 예컨대, 2'-플루오로 변형, 2'-O-메틸 변형, 또는 2'-H (데옥시) 변형을 포함한다. 일 구현예에서, 무염기 뉴클레오티드는 2'-O-메틸 변형을 포함한다. 다른 구현예에서, 무염기 뉴클레오티드는 2'-H 변형을 포함한다(즉, 데옥시 무염기 뉴클레오티드임).
특정 구현예에서, 본 발명의 RNAi 작제물은 그 전문이 본원에 참조로 포함되는 WIPO 공개 번호 WO 2020/123410에 기술된 패턴과 같은 특정 패턴에 따라 센스 및 안티센스 가닥에 혼입된 변형된 뉴클레오티드를 포함할 수 있다. 이러한 화학적 변형 패턴을 갖는 RNAi 작제물은 생체내에서 개선된 유전자 사일런싱 활성을 갖는 것으로 나타났다. 일 구현예에서, 본 발명의 RNAi 작제물은 적어도 15개의 염기쌍의 이중체 영역을 형성하도록 서로에 대해 충분히 상보적인 서열을 포함하는 센스 가닥과 안티센스 가닥을 포함하고,
· (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 2, 7, 및 14번의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이고;
· (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 8 내지 11 및 13번과 쌍을 이룬 위치에서의 센스 가닥의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이고;
· 센스 가닥과 안티센스 가닥은 각각 총 7개를 초과하는 2'-플루오로 변형된 뉴클레오티드를 갖지 않는다.
다른 구현예에서, 본 발명의 RNAi 작제물은 적어도 19개의 염기쌍의 이중체 영역을 형성하도록 서로에 대해 충분히 상보적인 서열을 포함하는 센스 가닥과 안티센스 가닥을 포함하고,
· (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 2, 7, 및 14번의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이고, (5' 말단으로부터 계산하는) 위치 4, 6, 10, 및 12번의 뉴클레오티드는 선택적으로 2'-플루오로 변형된 뉴클레오티드이고, 안티센스 가닥의 다른 모든 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드가 아닌 변형된 뉴클레오티드이고;
· (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 8 내지 11, 및 13번과 쌍을 이룬 위치에서의 센스 가닥의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이고, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 3 및 5번과 쌍을 이룬 위치에서의 센스 가닥의 뉴클레오티드는 임의로 2'-플루오로 변형된 뉴클레오티드이고; 센스 가닥의 다른 모든 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드가 아닌 변형된 뉴클레오티드이다.
이러한 구현예에서, 2'-플루오로 변형된 뉴클레오티드가 아닌 변형된 뉴클레오티드는 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 선택될 수 있다. 이러한 구현예 및 다른 구현예에서, 센스 가닥의 3' 말단, 5' 말단, 또는 3' 말단과 5' 말단 둘 다에서의 말단 뉴클레오티드는 무염기 뉴클레오티드 또는 데옥시리보뉴클레오티드일 수 있다. 이러한 구현예에서, 무염기 뉴클레오티드 또는 데옥시리보뉴클레오티드는 반전될 수 있다 - 즉, 천연의 3'-5' 뉴클레오티드간 연결 대신 3'-3' 뉴클레오티드간 연결(가닥의 3' 말단에 있을 때)을 통해 또는 5'-5' 뉴클레오티드간 연결(가닥의 5' 말단에 있을 때)을 통해 인접 뉴클레오티드에 연결될 수 있다.
임의의 전술한 구현예에서, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 2, 7, 12, 및 14번의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이다. 다른 구현예에서, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 2, 4, 7,12, 및 14번의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이다. 또 다른 구현예에서, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 2, 4, 6, 7, 12, 및 14번의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이다. 또 다른 구현예에서, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 2, 4, 6, 7, 10, 12, 및 14번의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이다. 대안적인 구현예에서, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 2, 7, 10, 12, 및 14번의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이다. 다른 특정 구현예에서, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 2, 4, 7, 10, 12, 및 14번의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이다.
임의의 전술한 구현예에서, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 3, 8 내지 11, 및 13번과 쌍을 이룬 위치에서의 센스 가닥의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이다. 일부 구현예에서, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 5, 8 내지 11, 및 13번과 쌍을 이룬 위치에서의 센스 가닥의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이다. 다른 구현예에서, (5' 말단으로부터 계산하는) 안티센스 가닥의 위치 3, 5, 8 내지 11, 및 13번과 쌍을 이룬 위치에서의 센스 가닥의 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드이다.
일부 구현예에서, 본 발명의 RNAi 작제물은 식 (A)로 표시되는 구조를 포함한다:
5'-(NA)x NL NL NL NL NL NL NF NL NF NF NF NF NL NL NM NL NM NL NT(n)y-3'
3'-(NB)z NL NL NL NL NL NF NL NM NL NM NL NL NF NM NL NM NL NF NL-5'
(A)
식 (A)에서, 5'에서 3'의 방향으로 열거된 윗 가닥은 센스 가닥이고 3'에서 5'의 방향으로 열거된 아랫 가닥은 안티센스 가닥이고; 각각의 NF는 2'-플루오로 변형된 뉴클레오티드이고; 각각의 NM은 독립적으로 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 선택된 변형된 뉴클레오티드를 나타내고; 각각의 NL은 독립적으로 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 선택된 변형된 뉴클레오티드를 나타내고; NT는 무염기 뉴클레오티드, 반전된 무염기 뉴클레오티드, 반전된 데옥시리보뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 선택된 변형된 뉴클레오티드를 나타낸다. x는 0 내지 4의 정수일 수 있으나, 단, x가 1, 2, 3, 또는 4인 경우, NA 뉴클레오티드 중 1개 이상은 무염기 뉴클레오티드, 반전된 무염기 뉴클레오티드, 반전된 데옥시리보뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 독립적으로 선택된 변형된 뉴클레오티드이다. NA 뉴클레오티드 중 1개 이상은 안티센스 가닥의 뉴클레오티드에 상보적일 수 있다. y는 0 내지 4의 정수일 수 있으나, 단, y가 1, 2, 3, 또는 4인 경우, 1개 이상의 n 뉴클레오티드는 안티센스 가닥의 뉴클레오티드와 염기쌍을 이루지 않는 변형된 또는 변형되지 않은 오버행 뉴클레오티드이다. z는 0 내지 4의 정수일 수 있으나, 단, z가 1, 2, 3, 또는 4인 경우, NB 뉴클레오티드 중 1개 이상은 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 독립적으로 선택된 변형된 뉴클레오티드이다. NB 뉴클레오티드 중 1개 이상은 센스 가닥에 존재할 때 NA 뉴클레오티드에 상보적일 수 있거나, 또는 센스 가닥의 뉴클레오티드와 염기쌍을 이루지 않는 오버행 뉴클레오티드일 수 있다.
RNAi 작제물이 식 (A)로 표시되는 구조를 포함하는 일부 구현예에서, 센스 가닥의 3' 말단에는 뉴클레오티드 오버행이 존재한다 - 즉, y는 1, 2, 3, 또는 4이다. 이러한 일 구현예에서, y는 2이다. 센스 가닥의 3' 말단에 2개의 뉴클레오티드의 오버행이 존재하는(즉, y가 2인) 구현예에서, x는 0이고 z는 2이거나, x는 1이고 z는 2이다. RNAi 작제물이 식 (A)로 표시되는 구조를 포함하는 다른 구현예에서, RNAi 작제물은 센스 가닥의 3' 말단 및 안티센스 가닥의 5' 말단에 평활 말단을 포함한다(즉, y는 0이다). 센스 가닥의 3' 말단에 뉴클레오티드 오버행이 존재하지 않는(즉, y가 0인) 이러한 구현예에서, (i) x는 2, z는 4, (ii) x는 3, z는 4, (iii) x는 0, z는 2, (iv) x는 1, z는 2이거나, 또는 (v) x는 2, z는 2이다. x가 0보다 큰 임의의 구현예에서, 센스 가닥의 5' 말단의 말단 뉴클레오티드인 NA 뉴클레오티드는 반전된 뉴클레오티드, 예컨대 반전된 무염기 뉴클레오티드 또는 반전된 데옥시리보뉴클레오티드일 수 있다.
RNAi 작제물이 식 (A)로 표시되는 구조를 포함하는 특정 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4 및 12번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이다. 다른 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4, 6, 및 12번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이다. 또 다른 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4, 6, 10, 및 12번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이다. RNAi 작제물이 식 (A)로 표시되는 구조를 포함하는 대안적인 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 10 및 12번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이다. 관련 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4, 10, 및 12번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이다. RNAi 작제물이 식 (A)로 표시되는 구조를 포함하는 다른 대안적인 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4, 6, 및 10번의 NM은 각각 2'-O-메틸 변형된 뉴클레오티드이고, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 12번의 NM은 2'-플루오로 변형된 뉴클레오티드이다. RNAi 작제물이 식 (A)로 표시되는 구조를 포함하는 일부 구현예에서, 센스 가닥의 각각의 NM은 2'-O-메틸 변형된 뉴클레오티드이다. 다른 구현예에서, 센스 가닥의 각각의 NM은 2'-플루오로 변형된 뉴클레오티드이다. RNAi 작제물이 식 (A)로 표시되는 구조를 포함하는 또 다른 구현예에서, 센스 가닥과 안티센스 가닥 둘 다의 각각의 NM은 2'-O-메틸 변형된 뉴클레오티드이다.
RNAi 작제물이 식 (A)로 표시되는 구조를 포함하는 임의의 전술한 구현예에서, 센스 가닥과 안티센스 가닥 둘 다의 각각의 NL은 2'-O-메틸 변형된 뉴클레오티드일 수 있다. 이러한 구현예 및 전술한 임의의 구현예에서, 식 (A)의 NT는 반전된 무염기 뉴클레오티드, 반전된 데옥시리보뉴클레오티드, 또는 2'-O-메틸 변형된 뉴클레오티드일 수 있다.
본 발명의 다른 구현예에서, 본 발명의 RNAi 작제물은 식 (B)로 표시되는 구조를 포함한다:
5'-(NA)x NL NL NL NL NM NL NF NF NF NF NL NL NL NL NL NL NL NL NT(n)y-3'
3'-(NB)z NL NL NL NM NL NF NL NM NL NL NM NM NM NM NL NM NL NF NL-5'
(B)
식 (B)에서, 5'에서 3'의 방향으로 열거된 윗 가닥은 센스 가닥이고 3'에서 5'의 방향으로 열거된 아랫 가닥은 안티센스 가닥이고; 각각의 NF는 2'-플루오로 변형된 뉴클레오티드를 나타내고; 각각의 NM은 독립적으로 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 선택된 변형된 뉴클레오티드를 나타내고; 각각의 NL은 독립적으로 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 선택된 변형된 뉴클레오티드를 나타내고; NT는 무염기 뉴클레오티드, 반전된 무염기 뉴클레오티드, 반전된 데옥시리보뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 선택된 변형된 뉴클레오티드를 나타낸다. x는 0 내지 4의 정수일 수 있으나, 단, x가 1, 2, 3, 또는 4인 경우, NA 뉴클레오티드 중 1개 이상은 무염기 뉴클레오티드, 반전된 무염기 뉴클레오티드, 반전된 데옥시리보뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 독립적으로 선택된 변형된 뉴클레오티드이다. NA 뉴클레오티드 중 1개 이상은 안티센스 가닥의 뉴클레오티드에 상보적일 수 있다. y는 0 내지 4의 정수일 수 있으나, 단, y가 1, 2, 3, 또는 4인 경우, 1개 이상의 n 뉴클레오티드는 안티센스 가닥의 뉴클레오티드와 염기쌍을 이루지 않는 변형된 또는 변형되지 않은 오버행 뉴클레오티드이다. z는 0 내지 4의 정수일 수 있으나, 단, z가 1, 2, 3, 또는 4인 경우, NB 뉴클레오티드 중 1개 이상은 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 및 데옥시리보뉴클레오티드로부터 독립적으로 선택된 변형된 뉴클레오티드이다. NB 뉴클레오티드 중 1개 이상은 센스 가닥에 존재할 때 NA 뉴클레오티드에 상보적일 수 있거나, 또는 센스 가닥의 뉴클레오티드와 염기쌍을 이루지 않는 오버행 뉴클레오티드일 수 있다.
RNAi 작제물이 식 (B)로 표시되는 구조를 포함하는 일부 구현예에서, 센스 가닥의 3' 말단에는 뉴클레오티드 오버행이 존재한다 - 즉, y는 1, 2, 3, 또는 4이다. 이러한 일 구현예에서, y는 2이다. 센스 가닥의 3' 말단에 2개의 뉴클레오티드의 오버행이 존재하는(즉, y가 2인) 구현예에서, x는 0이고 z는 2이거나, x는 1이고 z는 2이다. RNAi 작제물이 식 (B)로 표시되는 구조를 포함하는 다른 구현예에서, RNAi 작제물은 센스 가닥의 3' 말단 및 안티센스 가닥의 5' 말단에 평활 말단을 포함한다(즉, y는 0이다). 센스 가닥의 3' 말단에 뉴클레오티드 오버행이 존재하지 않는(즉, y가 0인) 이러한 구현예에서, (i) x는 2, z는 4, (ii) x는 3, z는 4, (iii) x는 0, z는 2, (iv) x는 1, z는 2이거나, 또는 (v) x는 2, z는 2이다. x가 0보다 큰 임의의 구현예에서, 센스 가닥의 5' 말단의 말단 뉴클레오티드인 NA 뉴클레오티드는 반전된 뉴클레오티드, 예컨대 반전된 무염기 뉴클레오티드 또는 반전된 데옥시리보뉴클레오티드일 수 있다.
RNAi 작제물이 식 (B)로 표시되는 구조를 포함하는 특정 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4, 6, 8, 9, 및 16번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이고, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 7 및 12번의 NM은 각각 2'-O-메틸 변형된 뉴클레오티드이다. 다른 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4 및 6번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이고, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 7 내지 9번의 NM은 각각 2'-O-메틸 변형된 뉴클레오티드이다. 또 다른 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4, 6, 8, 9, 및 16번의 NM은 각각 2'-O-메틸 변형된 뉴클레오티드이고, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 7 및 12번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이다. RNAi 작제물이 식 (B)로 표시되는 구조를 포함하는 대안적인 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4, 6, 8, 9, 및 12번의 NM은 각각 2'-O-메틸 변형된 뉴클레오티드이고, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 7 및 16번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이다. RNAi 작제물이 식 (B)로 표시되는 구조를 포함하는 다른 특정 구현예에서, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 7, 8, 9, 및 12번의 NM은 각각 2'-O-메틸 변형된 뉴클레오티드이고, 5' 말단으로부터 계산하는 안티센스 가닥의 위치 4, 6, 및 16번의 NM은 각각 2'-플루오로 변형된 뉴클레오티드이다. RNAi 작제물이 식 (B)로 표시되는 구조를 포함하는 이러한 구현예 및 다른 구현예에서, 센스 가닥의 NM은 2'-플루오로 변형된 뉴클레오티드이다. 대안적인 구현예에서, 센스 가닥의 NM은 2'-O-메틸 변형된 뉴클레오티드이다.
RNAi 작제물이 식 (B)로 표시되는 구조를 포함하는 임의의 전술한 구현예에서, 센스 가닥과 안티센스 가닥 둘 다의 각각의 NL은 2'-O-메틸 변형된 뉴클레오티드일 수 있다. 이러한 구현예 및 전술한 임의의 구현예에서, 식 (B)의 NT는 반전된 무염기 뉴클레오티드, 반전된 데옥시리보뉴클레오티드, 또는 2'-O-메틸 변형된 뉴클레오티드일 수 있다.
본 발명의 RNAi 작제물은 또한, 하나 이상의 변형된 뉴클레오티드간 연결을 포함할 수 있다. 본원에서 사용되는 바와 같이, 용어 "변형된 뉴클레오티드간 연결"은 천연 3'에서 5'의 포스포디에스테르 연결 이외의 뉴클레오티드간 연결을 지칭한다. 일부 구현예에서, 변형된 뉴클레오티드간 연결은 인-함유 뉴클레오티드간 연결, 예컨대 포스포트리에스테르, 아미노알킬 포스포트리에스테르, 알킬포스포네이트(예를 들어, 메틸포스포네이트, 3'-알킬렌 포스포네이트), 포스피네이트, 포스포라미데이트(예를 들어, 3'-아미노포스포라미데이트 및 아미노알킬포스포라미데이트), 포스포로티오에이트, 키랄 포스포로티오에이트, 포스포로디티오에이트, 티오노포스포라미데이트, 티오노알킬포스포네이트, 티오노알킬포스포트리에스테르, 및 보라노포스페이트이다. 일 구현예에서, 변형된 뉴클레오티드간 연결은 2' 내지 5' 포스포디에스테르 연결이다. 다른 구현예에서, 변형된 뉴클레오티드간 연결은 비-인-함유 뉴클레오티드간 연결이므로, 변형된 뉴클레오시드간 연결로 지칭될 수 있다. 이러한 비-인-함유 연결은 모르폴리노 연결 (뉴클레오시드의 당 부분으로부터 부분적으로 형성됨); 실록산 연결 (-O-Si(H)2-O-); 설파이드, 설폭사이드 및 설폰 연결; 포름아세틸 및 티오포름아세틸 연결; 알켄 함유 백본; 설파메이트 백본; 메틸렌메틸이미노(-CH2-N(CH3)-O-CH2-) 및 메틸렌히드라지노 연결; 설포네이트 및 설폰아미드 연결; 아미드 연결; 및 N, O, S 및 CH2 성분 부분이 혼합된 다른 것을 포함하지만, 이에 제한되지 않는다. 일 구현예에서, 변형된 뉴클레오시드간 연결은 펩타이드-기반 연결 (예를 들어, 아미노에틸글리신)이어서, 펩타이드 핵산 또는 PNA, 예컨대 미국 특허 제5,539,082호; 제5,714,331호; 및 제5,719,262호에 기재된 것들을 생성한다. 본 발명의 RNAi 작제물에 사용될 수 있는 다른 적당한 변형된 뉴클레오티드간 및 뉴클레오시드간 연결은 미국 특허 제6,693,187호, 미국 특허 제9,181,551호, 미국 특허 공개 번호 2016/0122761, 및 Deleavey and Damha, Chemistry and Biology, Vol. 19: 937-954, 2012에 기재되어 있으며, 이들은 그 전문이 본원에 참조로 포함된다.
특정 구현예에서, 본 발명의 RNAi 작제물은 하나 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 포스포로티오에이트 뉴클레오티드간 연결은 RNAi 작제물의 센스 가닥, 안티센스 가닥, 또는 양쪽 가닥에 존재할 수 있다. 예를 들어, 일부 구현예에서, 센스 가닥은 1, 2, 3, 4, 5, 6, 7, 8개, 또는 그 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 다른 구현예에서, 안티센스 가닥은 1, 2, 3, 4, 5, 6, 7, 8개, 또는 그 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 또 다른 구현예에서, 양쪽 가닥은 1, 2, 3, 4, 5, 6, 7, 8개, 또는 그 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. RNAi 작제물은 센스 가닥, 안티센스 가닥, 또는 양쪽 가닥의 3'-말단, 5'-말단, 또는 3'- 및 5'-말단 양쪽에 하나 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함할 수 있다. 예를 들어, 특정 구현예에서, RNAi 작제물은 센스 가닥, 안티센스 가닥, 또는 양쪽 가닥의 3'-말단에 약 1 내지 약 6개 또는 그 이상의 (예를 들어, 약 1, 2, 3, 4, 5, 6개 또는 그 이상의) 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 다른 구현예에서, RNAi 작제물은 센스 가닥, 안티센스 가닥, 또는 양쪽 가닥의 5'-말단에 약 1 내지 약 6개 또는 그 이상의 (예를 들어, 약 1, 2, 3, 4, 5, 6개 또는 그 이상의) 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 일 특정 구현예에서, 안티센스 가닥은 1개 이상 6개 이하의 포스포로티오에이트 뉴클레오티드간 연결을 포함하고, 센스 가닥은 1개 이상 4개 이하의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 다른 특정 구현예에서, 안티센스 가닥은 1개 이상 4개 이하의 포스포로티오에이트 뉴클레오티드간 연결을 포함하고, 센스 가닥은 1개 이상 2개 이하의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다.
일부 구현예에서, RNAi 작제물은 센스 가닥의 3' 말단의 말단 뉴클레오티드들 사이에 단일 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 다른 구현예에서, RNAi 작제물은 센스 가닥의 3' 말단의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 일 구현예에서, RNAi 작제물은 센스 가닥의 3' 말단의 말단 뉴클레오티드들 사이에 단일 포스포로티오에이트 뉴클레오티드간 연결 및 안티센스 가닥의 3' 말단의 말단 뉴클레오티드들 사이에 단일 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 다른 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 말단의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결(즉, 안티센스 가닥의 3' 말단에 있는 제1 및 제2 뉴클레오티드간 연결에 있는 포스포로티오에이트 뉴클레오티드간 연결)을 포함한다. 다른 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 또 다른 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결 및 센스 가닥의 5' 말단에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 또 다른 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결 및 센스 가닥의 3' 말단의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 다른 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결, 및 센스 가닥의 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결(즉, 안티센스 가닥의 5' 및 3' 말단 양쪽에서의 제1 및 제2 뉴클레오티드간 연결에 포스포로티오에이트 뉴클레오티드간 연결 및 센스 가닥의 5' 및 3' 말단 양쪽에서의 제1 및 제2 뉴클레오티드간 연결에 포스포로티오에이트 뉴클레오티드간 연결)을 포함한다. 또 다른 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결 및 센스 가닥의 3' 말단의 말단 뉴클레오티드들 사이에 단일 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 하나 또는 둘 모두의 가닥이 하나 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함하는 임의의 구현예에서, 가닥 내의 나머지 뉴클레오티드간 연결은 천연 3'에서 5'의 포스포디에스테르 연결일 수 있다. 예를 들어, 일부 구현예에서, 센스 및 안티센스 가닥의 각각의 뉴클레오티드간 연결은 포스포디에스테르 및 포스포로티오에이트로부터 선택되며, 여기서 적어도 하나의 뉴클레오티드간 연결은 포스포로티오에이트이다.
RNAi 작제물이 뉴클레오티드 오버행을 포함하는 구현예에서, 오버행에서의 2개 이상의 짝없는 뉴클레오티드가 포스포로티오에이트 뉴클레오티드간 연결에 의해 연결될 수 있다. 특정 구현예에서, 안티센스 가닥 및/또는 센스 가닥의 3' 말단에서 뉴클레오티드 오버행 내의 모든 짝없는 뉴클레오티드는 포스포로티오에이트 뉴클레오티드간 연결에 의해 연결된다. 다른 구현예에서, 안티센스 가닥 및/또는 센스 가닥의 5' 말단에서 뉴클레오티드 오버행 내의 모든 짝없는 뉴클레오티드는 포스포로티오에이트 뉴클레오티드간 연결에 의해 연결된다. 또 다른 구현예에서, 임의의 뉴클레오티드 오버행에서 모든 짝없는 뉴클레오티드는 포스포로티오에이트 뉴클레오티드간 연결에 의해 연결된다.
포스포로티오에이트 뉴클레오티드간 연결의 혼입은 올리고뉴클레오티드의 인 원자의 추가적인 키랄 중심을 도입하므로 각 포스포로티오에이트 뉴클레오티드간 연결에서 부분입체이성체 쌍(Rp 및 Sp)을 생성한다. 부분입체이성체 또는 부분입체이성질체는 동일한 분자식 및 결합된 원자의 서열을 갖지만 공간에서 원자의 3차원 배향이 다른 화합물의 상이한 구성이다. 거울상이성체와 달리, 부분입체이성체는 서로 거울상이 아니다. 각 키랄 포스페이트 원자는 "R" 배열(Rp) 또는 "S" 배열(Sp)로 존재할 수 있다. 특정 구현예에서, 본 발명의 RNAi 작제물은 키랄 포스페이트가 주로 Rp 또는 Sp 배열로 존재하도록 선택되는 하나 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함할 수 있다. 예를 들어, RNAi 작제물이 하나 이상의 포스포로티오에이트 뉴클레오티드간 연결을 갖는 일부 구현예에서, 키랄 포스페이트의 적어도 약 70%, 적어도 약 75%, 적어도 약 80%, 적어도 약 85%, 적어도 약 90%, 또는 적어도 약 95%가 Sp 배열로 존재한다. RNAi 작제물이 하나 이상의 포스포로티오에이트 뉴클레오티드간 연결을 갖는 다른 구현예에서, 키랄 포스페이트의 적어도 약 70%, 적어도 약 75%, 적어도 약 80%, 적어도 약 85%, 적어도 약 90%, 또는 적어도 약 95%가 Rp 배열로 존재한다. RNAi 작제물의 모든 키랄 포스페이트는 Sp 배열 또는 Rp 배열로 존재할 수 있다(즉, RNAi 작제물은 입체순수함). 일 특정 구현예에서, RNAi 작제물의 모든 키랄 포스페이트는 Sp 배열로 존재한다. 다른 특정 구현예에서, RNAi 작제물의 모든 키랄 포스페이트는 Rp 배열로 존재한다.
특정 구현예에서, RNAi 작제물의 키랄 포스페이트는 센스 가닥 또는 안티센스 가닥의 상이한 위치에서 상이한 구성을 가질 수 있다. RNAi 작제물이 안티센스 가닥의 5' 말단에 1개 또는 2개의 포스포로티오에이트 뉴클레오티드간 연결을 포함하는 이러한 일 구현예에서, 안티센스 가닥의 5' 말단의 키랄 포스페이트는 Rp 배열로 존재할 수 있다. RNAi 작제물이 안티센스 가닥의 3' 말단에 1개 또는 2개의 포스포로티오에이트 뉴클레오티드간 연결을 포함하는 이러한 다른 구현예에서, 안티센스 가닥의 3' 말단의 키랄 포스페이트는 Sp 배열로 존재할 수 있다. 특정 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결 및 센스 가닥의 3' 말단의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함하고, 안티센스 가닥의 5' 말단의 키랄 포스페이트는 Rp 배열로 존재하고, 안티센스 가닥의 3' 말단의 키랄 포스페이트는 Sp 배열로 존재하고, 센스 가닥의 3' 말단의 키랄 포스페이트는 Rp 또는 Sp 배열로 존재할 수 있다. 다른 특정 구현예에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결 및 센스 가닥의 3' 말단의 말단 뉴클레오티드들 사이에 단일 포스포로티오에이트 뉴클레오티드간 연결을 포함하고, 안티센스 가닥의 5' 말단의 키랄 포스페이트는 Rp 배열로 존재하고, 안티센스 가닥의 3' 말단의 키랄 포스페이트는 Sp 배열로 존재하고, 센스 가닥의 3' 말단의 키랄 포스페이트는 Rp 또는 Sp 배열로 존재할 수 있다. 올리고뉴클레오티드 합성 중 포스포로티오에이트 연결의 입체화학을 제어하는 방법은 당업자에게 공지되어 있고, 문헌[Nawrot and Rebowska, Curr Protoc Nucleic Acid Chem. 2009, Chapter 4:. doi:10.1002/0471142700.nc0434s362009; Jahns et al., Nat. Commun, Vol. 6: 6317, 2015; Knouse et al., Science, Vol. 361: 1234-1238, 2018; 및 Sakamuri et al., Chembiochem, Vol. 21(9): 1304-1308, 2020]에 기재된 방법을 포함할 수 있다.
본 발명의 RNAi 작제물의 일부 구현예에서, 센스 가닥, 안티센스 가닥, 또는 안티센스 및 센스 가닥 둘 다의 5' 말단은 포스페이트 모이어티를 포함한다. 본원에서 사용되는 바와 같이, 용어 "포스페이트 모이어티"는 변형되지 않은 포스페이트(-O-P=O)(OH)OH) 뿐만 아니라 변형된 포스페이트를 포함하는 말단 포스페이트 기를 지칭한다. 변형된 포스페이트는 하나 이상의 O 및 OH 기가 H, O, S, N(R), 또는 알킬(예를 들어 C1 내지 C12)로 대체된 포스페이트를 포함하며, 여기서 R은 H, 아미노 보호 기 또는 치환되지 않은 또는 치환된 알킬(예를 들어 C1 내지 C12)이다. 예시적인 포스페이트 모이어티는 5'-모노포스페이트; 5'디포스페이트; 5'-트리포스페이트; (7-메틸화 또는 비-메틸화된) 5'-구아노신 캡; 5'-아데노신 캡 또는 임의의 다른 변형된 또는 변형되지 않은 뉴클레오티드 캡 구조; 5'-모노티오포스페이트(포스포로티오에이트); 5'-모노디티오포스페이트(포스포로디티오에이트); 5'-알파-티오트리포스페이트; 5'-감마-티오트리포스페이트, 5'-포스포라미데이트; 5'-비닐포스페이트; 5'-알킬포스포네이트(예를 들어, 알킬 = 메틸, 에틸, 이소프로필, 프로필 등); 및 5'-알킬에테르포스포네이트(예를 들어, 알킬에테르 = 메톡시메틸, 에톡시메틸, 등)를 포함하지만, 이에 제한되지 않는다.
본 발명의 RNAi 작제물에 통합될 수 있는 변형된 뉴클레오티드는 본원에 기재된 하나 이상의 화학적 변형을 가질 수 있다. 예를 들어, 변형된 뉴클레오티드는 리보스 당에 대한 변형뿐만 아니라 핵염기에 대한 변형을 가질 수 있다. 예로서, 변형된 뉴클레오티드는 2' 당 변형(예를 들어, 2'-플루오로 또는 2'-O-메틸)을 포함할 수 있으며, 변형된 염기(예를 들어 5-메틸 시토신 또는 슈도우라실)를 포함할 수 있다. 다른 구현예에서, 변형된 뉴클레오티드는 변형된 뉴클레오티드가 폴리뉴클레오티드에 통합될 때 변형된 뉴클레오티드간 또는 뉴클레오시드간 연결을 생성하는 5' 포스페이트에 대한 변형과 조합된 당 변형을 포함할 수 있다. 예를 들어, 일부 구현예에서, 변형된 뉴클레오티드는 당 변형, 예컨대 2'-플루오로 변형, 2'-O-메틸 변형, 또는 이환식 당 변형, 뿐만 아니라 5' 포스포로티오에이트 기를 포함할 수 있다. 따라서, 일부 구현예에서, 본 발명의 RNAi 작제물의 하나 또는 둘 모두의 가닥은 2' 변형된 뉴클레오티드 또는 BNA 및 포스포로티오에이트 뉴클레오티드간 연결의 조합을 포함한다. 특정 구현예에서, 본 발명의 RNAi 작제물의 센스 및 안티센스 가닥 둘 모두는 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 및 포스포로티오에이트 뉴클레오티드간 연결의 조합을 포함한다. 변형된 뉴클레오티드 및 뉴클레오티드간 연결을 포함하는 예시적인 RNAi 작제물은 표 2에 제시되어 있다.
본 발명의 RNAi 작제물은 당업계에 공지된 기술, 예를 들어 통상적인 핵산 고상 합성법을 사용하여 용이하게 제조될 수 있다. RNAi 작제물의 폴리뉴클레오티드는 표준 뉴클레오티드 또는 뉴클레오시드 전구체(예를 들어, 포스포라미다이트)를 사용하여 적합한 핵산 합성기에 조립될 수 있다. 자동화된 핵산 합성기는 Applied Biosystems(Foster City, CA)로부터의 DNA/RNA 합성기, BioAutomation(Irving,TX)로부터의 MerMade 합성기, 및 GE Healthcare Life Sciences(Pittsburgh, PA)로부터의 OligoPilot 합성기를 포함하여, 여러 공급업체에서 상업적으로 시판된다. 본 발명의 RNAi 작제물을 합성하는 예시적인 방법은 실시예 2에 기술되어 있다.
2' 실릴 보호기는 포스포라미다이트 화학을 통해 올리고뉴클레오티드를 합성하기 위해 리보뉴클레오시드의 5' 위치에서 산 불안정한 디메톡시트리틸(DMT)과 함께 사용될 수 있다. 최종 탈보호 조건은 RNA 생성물을 현저하게 분해하지 않는 것으로 알려져 있다. 모든 합성은 임의의 자동 또는 수동 합성기에서 대규모, 중규모, 또는 소규모로 수행될 수 있다. 합성은 또한 다수의 웰 플레이트, 컬럼 또는 유리 슬라이드에서 수행될 수 있다.
2'-O-실릴기는 플루오라이드 이온에의 노출을 통해 제거될 수 있으며, 플루오라이드 이온의 임의의 공급원, 예를 들어, 무기 반대이온과 짝을 이루는 플루오라이드 이온을 함유하는 염, 예를 들어, 세슘 플루오라이드 및 칼륨 플루오라이드 또는 유기 반대이온과 짝을 이루는 플루오라이드 이온을 함유하는 염, 예를 들어, 테트라알킬암모늄 플루오라이드를 포함할 수 있다. 탈보호 반응에서 크라운 에테르 촉매가 무기 플루오라이드와 함께 사용될 수 있다. 예시적인 플루오라이드 이온 공급원은 테트라부틸암모늄 플루오라이드 또는 아미노하이드로플루오라이드(예를 들어, 이극성 비양자성 용매, 예를 들어, 디메틸포름아미드에서 수성 HF를 트리에틸아민과 조합함)이다.
포스파이트 트리에스테르 및 포스포트리에스테르에 사용하기 위한 보호기의 선택은 플루오라이드에 대한 트리에스테르의 안정성을 변경할 수 있다. 포스포트리에스테르 또는 포스파이트트리에스테르의 메틸 보호는 플루오라이드 이온에 대한 연결을 안정화시키고 공정 수율을 향상시킬 수 있다.
리보뉴클레오시드는 반응성 2' 히드록실 치환기를 갖기 때문에, 5'-O-디메톡시트리틸 보호기에 직교하는 보호기, 예를 들어, 산으로 처리하기에 안정적인 보호기로 RNA에서 반응성 2' 위치를 보호하는 것이 바람직할 수 있다. 실릴 보호기는 이 기준을 만족시키며, 최종 플루오르화물 탈보호 단계에서 용이하게 제거되어 최소 RNA 분해를 초래할 수 있다.
테트라졸 촉매는 표준 포스포라미다이트 커플링 반응에 사용될 수 있다. 예시적인 촉매는 예를 들어, 테트라졸, S-에틸-테트라졸, 벤질티오테트라졸, p-니트로페닐테트라졸을 포함한다.
당업자에 의해 이해될 수 있는 바와 같이, 본원에 기재된 RNAi 작제물을 합성하는 추가의 방법은 당업자에게 명백할 것이다. 또한, 원하는 화합물을 제공하기 위해 다양한 합성 단계가 교대 서열 또는 순서로 수행될 수 있다. 본원에 기재된 RNAi 작제물을 합성하는데 유용한 다른 합성 화학 변형, (예를 들어, 염기에 존재하는 히드록실, 아미노, 등을 위한) 보호기 및 보호기 방법론(보호 및 탈 보호)은 당업계에 공지되어 있으며, 예를 들어, 예컨대 문헌[R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2d. Ed., John Wiley and Sons (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995)] 및 이들의 후속판에 기술된 것들을 포함한다. RNAi 작제물의 맞춤형 합성은 Dharmacon, Inc.(Lafayette, CO), AxoLabs GmbH(Kulmbach, 독일) 및 Ambion, Inc.(Foster City, CA)를 포함한 여러 판매회사에서도 이용 가능하다.
본 발명의 RNAi 작제물은 리간드를 포함할 수 있다. 본원에서 사용되는 바와 같이, "리간드"는 다른 화합물 또는 분자와 직접 또는 간접적으로 상호작용할 수 있는 임의의 화합물 또는 분자를 지칭한다. 리간드와 또 다른 화합물 또는 분자의 상호작용은 생물학적 반응을 유발할 수 있거나(예를 들어, 신호 전달 캐스케이드를 개시하거나, 수용체 매개된 세포내이입을 유도하거나) 또는 물리적 연관일 수 있다. 리간드는 부착된 이중-가닥 RNA 분자의 하나 이상의 특성, 예컨대 RNA 분자의 약력학적, 약동학적, 결합, 흡수, 세포 분포, 세포 흡수, 전하 및/또는 제거 특성을 변형시킬 수 있다.
리간드는 혈청 단백질(예를 들어, 인간 혈청 알부민, 저밀도 지단백질, 글로불린), 콜레스테롤 모이어티, 비타민(비오틴, 비타민 E, 비타민 B12), 폴레이트 모이어티, 스테로이드, 담즙산(예를 들어, 콜린 산), 지방산(예를 들어, 팔미트 산, 미리스트 산), 탄수화물(예를 들어, 덱스트란, 풀루란, 키틴, 키토산, 이눌린, 시클로덱스트린 또는 히알루론산), 글리코시드, 인지질 또는 항체 또는 이의 결합 단편(예를 들어, 특정 세포 유형, 예컨대 간에 RNAi 작제물을 표적화하는 항체 또는 결합 단편)을 포함할 수 있다. 리간드의 다른 예는 염료, 삽입제(예를 들어, 아크리딘), 가교제(예를 들어, 소랄렌, 미토마이신 C), 포르피린(TPPC4, 텍사피린, 사피린), 다환 방향족 탄화수소(예를 들어, 페나진, 디하이드로페나진), 인공 엔도뉴클레아제(예를 들어, EDTA), 친유성 분자, 예를 들어 아다만탄 아세트산, 1-피렌 부티르산, 디하이드로테스토스테론, 1,3-비스-O(헥사데실)글리세롤, 제라닐옥시헥실기, 헥사데실글리세롤, 보르네올, 멘톨, 1,3-프로판디올, 헵타데실기, O3-(올레오일)리토콜산, O3-(올레오일)콜레산, 디메톡시트리틸 또는 페녹사진), 펩타이드(예를 들어, 안테나피디아 펩타이드, Tat 펩타이드, RGD 펩타이드), 알킬화제, 중합체, 예컨대 폴리에틸렌 글리콜(PEG)(예를 들어, PEG-40K), 폴리아미노산, 및 폴리아민(예를 들어, 스페르민, 스퍼미딘)을 포함한다.
특정 구현예에서, 리간드는 엔도좀분해 특성을 갖는다. 엔도좀분해 리간드는 엔도좀의 용해 및/또는 본 발명의 RNAi 작제물 또는 이의 성분의 엔도좀에서 세포의 세포질로의 이동을 촉진한다. 엔도좀분해 리간드는 pH 의존적 막 활성 및 발암성을 나타내는 다중 양이온성 펩타이드 또는 펩티도미메틱일 수 있다. 일 구현예에서, 엔도좀분해 리간드는 엔도좀 pH에서 이의 활성 형태를 가정한다. "활성" 입체형태는 엔도좀분해 리간드가 엔도좀의 용해 및/또는 본 발명의 RNAi 작제물 또는 이의 성분의 엔도좀에서 세포의 세포질로의 이동을 촉진하는 입체형태이다. 예시적인 엔도좀분해 리간드는 GALA 펩타이드(문헌[Subbarao et al., Biochemistry, Vol. 26: 2964-2972, 1987]), EALA 펩타이드(문헌[Vogel et al., J. Am. Chem. Soc., Vol. 118: 1581-1586, 1996]), 및 이들의 유도체(문헌[Turk et al., Biochem. Biophys. Acta, Vol. 1559: 56-68, 2002])를 포함한다. 일 구현예에서, 엔도좀분해 성분은 pH의 변화에 반응하여 전하의 변화 또는 양자화를 겪을 화학기(예를 들어, 아미노산)를 함유할 수 있다. 엔도좀분해 성분은 선형 또는 분지형일 수 있다.
일부 구현예에서, 리간드는 지질 또는 다른 소수성 분자를 포함한다. 일 구현예에서, 리간드는 콜레스테롤 부분 또는 다른 스테로이드를 포함한다. 콜레스테롤 접합된 올리고뉴클레오티드는 이들의 비접합된 것보다 더 활성인 것으로 보고되었다(Manoharan, Antisense Nucleic Acid Drug Development, Vol. 12: 103-228, 2002). 콜레스테롤 모이어티 및 핵산 분자와의 접합을 위한 다른 지질을 포함하는 리간드가 또한, 미국 특허 제7,851,615호; 제7,745,608호; 및 제7,833,992호에 기재되어 있으며, 이들 모두는 그 전문이 본원에 참조로 포함된다. 다른 구현예에서, 리간드는 폴레이트 모이어티를 포함한다. 폴레이트 모이어티에 접합된 폴리뉴클레오티드는 수용체-매개 세포내이입 경로를 통해 세포에 의해 흡수될 수 있다. 이러한 폴레이트-폴리뉴클레오티드 접합체는 그 전문이 본원에 참조로 포함되는, 미국 특허 번호 제8,188,247호에 기재되어 있다.
특정 구현예에서, 특히 간에서 mARC1 단백질의 발현을 감소시키기 위해 본 발명의 RNAi 작제물을 간 세포에 특이적으로 전달하는 것이 바람직하다. 따라서, 특정 구현예에서, 리간드는 아래에서 더욱 상세히 기술된 바와 같은 다양한 접근법을 이용하여 간세포에 대해 특이적으로 RNAi 작제물의 전달을 표적화한다. 특정 구현예에서, RNAi 작제물은 표면 발현된 아시알로당단백질 수용체(ASGR) 또는 이의 성분(예를 들어 ASGR1, ASGR2)에 결합하는 리간드로 간세포로 표적화된다.
일부 구현예에서, RNAi 작제물은 간 세포 표면에 발현된 단백질에 결합하거나 이와 상호작용하는 리간드를 사용함으로써 간을 특이적으로 표적화할 수 있다. 예를 들어, 특정 구현예에서, 리간드는 간세포상에서 발현된 수용체, 예컨대 아시알로당단백질 수용체 및 LDL 수용체에 특이적으로 결합하는 항원 결합 단백질(예를 들어, 항체 또는 이의 결합 단편(예를 들어, Fab, scFv))을 포함할 수 있다. 일 특정 구현예에서, 리간드는 ASGR1 및/또는 ASGR2에 특이적으로 결합하는 항체 또는 이의 결합 단편을 포함한다. 다른 구현예에서, 리간드는 ASGR1 및/또는 ASGR2에 특이적으로 결합하는 항체의 Fab 단편을 포함한다. "Fab 단편"은 1개의 면역글로불린 경쇄(즉, 경쇄 가변 영역(VL) 및 불변 영역(CL)) 및 1개의 면역글로불린 중쇄의 CH1 영역 및 가변 영역(VH)으로 구성된다. 다른 구현예에서, 리간드는 ASGR1 및/또는 ASGR2에 특이적으로 결합하는 항체의 단쇄 가변 항체 단편(scFv 단편)을 포함한다. "scFv 단편"은 항체의 VH 및 VL 영역을 포함하고, 여기서 이들 영역은 단일 폴리펩타이드 쇄에 존재하고, 선택적으로 Fv가 항원 결합을 위하여 원하는 구조를 형성할 수 있게 하는 펩타이드 링커를 VH 및 VL 영역 사이에 포함한다. 본 발명의 RNAi 작제물을 간으로 표적화하는 리간드로서 이용될 수 있는 ASGR1에 특이적으로 결합하는 예시적인 항체 및 이의 결합 단편은 WIPO 공개 번호 제2017/058944호에 기재되어 있으며, 이는 그 전문이 본원에 참고로 포함된다. ASGR1, LDL 수용체, 또는 본 발명의 RNAi 작제물에서 리간드로 사용하기에 적합한 기타 간 표면 발현 단백질에 특이적으로 결합하는 기타 항체 또는 이의 결합 단편은 상업적으로 이용 가능하다.
특정 구현예에서, 리간드는 탄수화물을 포함한다. "탄수화물"은 각각의 탄소 원자에 결합된 산소, 질소 또는 황 원자를 갖는 적어도 6개의 탄소 원자(직쇄, 분지쇄 또는 환형일 수 있음)를 갖는 하나 이상의 단당류 단위로 이루어진 화합물을 지칭한다. 탄수화물은 당(예를 들어, 단당류, 이당류, 삼당류, 사당류 및 약 4, 5, 6, 7, 8 또는 9개의 단당류 단위를 함유하는 올리고당류) 및 다당류, 예컨대 전분, 글리코겐, 셀룰로오스 및 다당류 검을 포함하지만, 이에 제한되지는 않는다. 일부 구현예에서, 탄수화물은 펜토스, 헥소오스, 또는 헵토스로부터 선택된 단당류 및 이러한 단당류 단위를 포함하는 이당류 및 삼당류이다. 다른 구현예에서, 리간드에 혼입된 탄수화물은 아미노 당, 예컨대 갈락토사민, 글루코사민, N-아세틸갈락토사민, 및 N-아세틸글루코사민이다.
일부 구현예에서, 리간드는 헥소오스 또는 헥소사민을 포함한다. 헥소오스는 글루코스, 갈락토스, 만노스, 푸코스, 또는 프룩토스로부터 선택될 수 있다. 헥소사민은 프룩토사민, 갈락토사민, 글루코사민, 또는 만노사민으로부터 선택될 수 있다. 특정 구현예에서, 리간드는 글루코스, 갈락토스, 갈락토사민, 또는 글루코사민을 포함한다. 일 구현예에서, 리간드는 글루코스, 글루코사민, 또는 N-아세틸글루코사민을 포함한다. 다른 구현예에서, 리간드는 갈락토스, 갈락토사민, 또는 N-아세틸-갈락토사민을 포함한다. 특정 구현예에서, 리간드는 N-아세틸-갈락토사민을 포함한다. 글루코스, 갈락토스, 및 N-아세틸-갈락토사민(GalNAc)을 포함하는 리간드는 간세포의 표면에서 발현된 ASGR에 결합하므로 이러한 리간드가 화합물을 간세포로 표적화하는 데 특히 효과적이다. 예를 들어, 문헌[D’Souza and Devarajan, J. Control Release, Vol. 203: 126-139, 2015] 참고. 본 발명의 RNAi 작제물에 혼입될 수 있는 GalNAc- 또는 갈락토스-함유 리간드의 예는 미국 특허 제7,491,805호; 제8,106,022호; 및 제8,877,917호; 미국 특허 공개 번호 20030130186; 및 WIPO 공개 번호 WO2013166155에 기재되어 있으며, 이들 모두는 그 전문이 본원에 참조로 포함된다.
특정 구현예에서, 리간드는 다가 탄수화물 모이어티를 포함한다. 본원에서 사용되는 바와 같이, "다가 탄수화물 모이어티"는 다른 분자와 독립적으로 결합하거나 상호작용할 수 있는 2개 이상의 탄수화물 단위를 포함하는 모이어티를 지칭한다. 예를 들어, 다가 탄수화물 모이어티는 2개 이상의 상이한 분자 또는 동일한 분자 상의 2개 이상의 상이한 부위에 결합할 수 있는 탄수화물로 조성된 둘 이상의 결합 도메인을 포함한다. 탄수화물 모이어티의 원자가는 탄수화물 모이어티 내의 개별 결합 도메인의 수를 나타낸다. 예를 들어, 탄수화물 모이어티와 관련하여 용어 "1가", "2가", "3가" 및 "4가"는 각각 1, 2, 3 및 4개의 결합 도메인을 갖는 탄수화물 모이어티를 지칭한다. 다가 탄수화물 모이어티는 다가 락토오스 모이어티, 다가 갈락토스 모이어티, 다가 글루코스 모이어티, 다가 N-아세틸-갈락토사민 모이어티, 다가 N-아세틸-글루코사민 모이어티, 다가 만노스 모이어티, 또는 다가 푸코스 모이어티를 포함할 수 있다. 일부 구현예에서, 리간드는 다가 갈락토스 모이어티를 포함한다. 다른 구현예에서, 리간드는 다가 N-아세틸-갈락토사민 모이어티를 포함한다. 이러한 구현예 및 다른 구현예에서, 다가 탄수화물 모이어티는 2가, 3가, 또는 4가일 수 있다. 이러한 구현예에서, 다가 탄수화물 모이어티는 바이-안테너리(bi-antennary) 또는 트리-안테너리(tri-antennary)일 수 있다. 일 특정 구현예에서, 다가 N-아세틸-갈락토사민 모이어티는 3가 또는 4가이다. 다른 특정 구현예에서, 다가 갈락토스 모이어티는 3가 또는 4가이다. 본 발명의 RNAi 작제물에 혼입하기 위한 예시적인 3가 및 4가 GalNAc-함유 리간드는 하기에 상세하게 기재되어 있다.
리간드는 RNAi 작제물의 RNA 분자에 직접 또는 간접적으로 부착되거나 접합될 수 있다. 예를 들어, 일부 구현예에서, 리간드는 RNAi 작제물의 센스 또는 안티센스 가닥에 직접 공유적으로 부착된다. 다른 구현예에서, 리간드는 링커를 통해 RNAi 작제물의 센스 또는 안티센스 가닥에 공유적으로 부착된다. 리간드는 본 발명의 RNAi 작제물의 폴리뉴클레오티드(예를 들어, 센스 가닥 또는 안티센스 가닥)의 핵염기, 당 모이어티, 또는 뉴클레오티드간 연결에 부착될 수 있다. 퓨린 핵염기 또는 이의 유도체에 대한 접합 또는 부착은 내환식 및 외환식 원자를 포함하는 임의의 위치에서 일어날 수 있다. 특정 구현예에서, 퓨린 핵염기의 2-, 6-, 7-, 또는 8-위치는 리간드에 부착된다. 피리미딘 핵염기 또는 이의 유도체에 대한 접합 또는 부착은 또한 임의의 위치에서 일어날 수 있다. 일부 구현예에서, 피리미딘 핵염기의 2-, 5-, 및 6-위치는 리간드에 부착될 수 있다. 뉴클레오티드의 당 모이어티에 대한 접합 또는 부착은 임의의 탄소 원자에서 일어날 수 있다. 리간드에 부착될 수 있는 당 모이어티의 예시적인 탄소 원자는 2', 3', 및 5' 탄소 원자를 포함한다. 1' 위치는 또한 무염기 뉴클레오티드와 같은 리간드에 부착될 수 있다. 뉴클레오티드간 연결은 또한, 리간드 부착을 지지할 수 있다. 인-함유 연결(예를 들어, 포스포디에스테르, 포스포로티오에이트, 포스포로디티오테이트, 포스포로아미데이트 등)의 경우, 리간드는 인 원자에 직접 또는 인 원자에 결합된 O, N, 또는 S 원자에 부착될 수 있다. 아민- 또는 아미드-함유 뉴클레오시드간 연결(예를 들어, PNA)의 경우, 리간드는 아민 또는 아미드의 질소 원자 또는 인접한 탄소 원자에 부착될 수 있다.
일부 구현예에서, 리간드는 센스 또는 안티센스 가닥의 3' 또는 5' 말단에 부착될 수 있다. 특정 구현예에서, 리간드는 센스 가닥의 5' 말단에 공유적으로 부착된다. 이러한 구현예에서, 리간드는 센스 가닥의 5'-말단 뉴클레오티드에 부착된다. 이러한 구현예 및 다른 구현예에서, 리간드는 센스 가닥의 5'-말단 뉴클레오티드의 5'-위치에 부착된다. 반전된 무염기 뉴클레오티드가 센스 가닥의 5' 말단 뉴클레오티드이고 5'-5' 뉴클레오티드간 연결을 통해 인접 뉴클레오티드에 연결되는 구현예에서, 리간드는 반전된 무염기 뉴클레오티드의 3'-위치에 부착될 수 있다. 다른 구현예에서, 리간드는 센스 가닥의 3' 말단에 공유적으로 부착된다. 예를 들어, 일부 구현예에서, 리간드는 센스 가닥의 3'-말단 뉴클레오티드에 부착된다. 이러한 특정 구현예에서, 리간드는 센스 가닥의 3'-말단 뉴클레오티드의 3'-위치에 부착된다. 반전된 무염기 뉴클레오티드가 센스 가닥의 3' 말단 뉴클레오티드이고 3'-3' 뉴클레오티드간 연결을 통해 인접 뉴클레오티드에 연결되는 구현예에서, 리간드는 반전된 무염기 뉴클레오티드의 5'-위치에 부착될 수 있다. 대안적인 구현예에서, 리간드는 센스 가닥의 3' 말단 근처에, 그러나 하나 이상의 말단 뉴클레오티드 전에(즉 1, 2, 3, 또는 4 말단 뉴클레오티드 전에) 부착된다. 일부 구현예에서, 리간드는 센스 가닥의 3'-말단 뉴클레오티드의 당의 2'-위치에 부착된다. 다른 구현예에서, 리간드는 센스 가닥의 5'-말단 뉴클레오티드의 당의 2'-위치에 부착된다.
특정 구현예에서, 리간드는 링커를 통해 센스 또는 안티센스 가닥에 부착된다. "링커"는 리간드를 RNAi 작제물의 폴리뉴클레오티드 성분에 공유 결합시키는 원자 또는 원자 그룹이다. 링커는 약 1 내지 약 30개 원자 길이, 약 2 내지 약 28개 원자 길이, 약 3 내지 약 26개 원자 길이, 약 4 내지 약 24개 원자 길이, 약 6 내지 약 20개 원자 길이, 약 7 내지 약 20개 원자 길이, 약 8 내지 약 20개 원자 길이, 약 8 내지 약 18개 원자 길이, 약 10 내지 약 18개 원자 길이, 및 약 12 내지 약 18개 원자 길이일수 있다. 일부 구현예에서, 링커는 이작용성 연결 모이어티를 포함할 수 있으며, 이는 일반적으로 2개의 작용기를 갖는 알킬 모이어티를 포함한다. 작용기 중 하나는 관심 화합물(예를 들어, RNAi 작제물의 센스 또는 안티센스 가닥)에 결합하도록 선택되고, 다른 하나는 본원에 기재된 리간드와 같은 임의의 선택된 기를 본질적으로 결합하도록 선택된다. 특정 구현예에서, 링커는 사슬 구조 또는 또는 반복 단위의 올리고머, 예컨대 에틸렌 글리콜 또는 아미노산 단위를 포함한다. 이작용성 연결 모이어티에 전형적으로 사용될 수 있는 작용기의 예는 친핵성 기와 반응하기 위한 친전자체 및 친전자성기와 반응하기 위한 친핵체를 포함하지만, 이에 제한되지 않는다. 일부 구현예에서, 이작용성 연결 모이어티는 아미노, 히드록실, 카르복실산, 티올, 불포화(예를 들어, 이중 또는 삼중 결합) 등을 포함한다.
본 발명의 RNAi 작제물에서 센스 또는 안티센스 가닥에 리간드를 부착시키는데 사용될 수 있는 링커는 피롤리딘, 8-아미노-3,6-디옥사옥탄산, 숙신이미딜 4-(N-말레이미도메틸)시클로헥산-1-카르복실레이트, 6-아미노헥산산, 치환된 C1-C10 알킬, 치환된 또는 비치환된 C2-C10 알케닐 또는 치환된 또는 비치환된 C2-C10 알키닐을 포함하지만, 이에 제한되지 않는다. 이러한 링커에 대한 적합한 치환기는 히드록실, 아미노, 알콕시, 카르복시, 벤질, 페닐, 니트로, 티올, 티오알콕시, 할로겐, 알킬, 아릴, 알케닐 및 알키닐을 포함하지만, 이에 제한되지 않는다.
특정 구현예에서, 링커는 절단가능하다. 절단성 링커는 세포 외부에서 충분히 안정하지만, 표적 세포로 진입시 절단되어, 링커가 함께 유지되는 두 부분을 해제하는 링커이다. 일부 구현예에서, 절단성 링커는 표적 세포에서, 또는 대상체의 혈액에서보다 제1 기준 조건(예를 들어, 세포내 조건을 모방하거나 나타내도록 선택될 수 있음) 하에, 또는 제2 기준 조건(예를 들어, 혈액 또는 혈청에서 발견된 조건을 모방하거나 나타내도록 선택될 수 있음) 하에, 적어도 10배, 20배, 30배, 40배, 50배, 60배, 70배, 80배, 90배, 또는 그 이상, 또는 적어도 100배 더 빨리 절단된다.
절단성 링커는 절단제, 예를 들어 pH, 산화환원 전위 또는 분해성 분자의 존재에 민감하다. 일반적으로, 절단제는 혈청 또는 혈액보다 세포 내에서 더 우세하거나 더 높은 수준 또는 활성으로 발견된다. 이러한 분해제의 예에는, 특정 기질에 대해 선택되거나, 또는 기질 특이성이 없는 산화환원제, 예를 들어 산화 또는 환원성 효소 또는 환원에 의해 산화환원 절단성 링커를 분해할 수 있는, 세포에 존재하는 환원제 예컨대 머캅탄; 에스테라제; 산성 환경, 예를 들어 pH 5 이하를 야기하는 환경을 생성할 수 있는 엔도좀 또는 작용제; 일반적인 산, 펩티다제(기질 특이적일 수 있음) 및 포스파타제로서 작용함으로써 산 절단성 링커를 가수분해 또는 분해할 수 있는 효소가 포함된다.
절단성 링커는 pH에 민감한 모이어티를 포함할 수 있다. 인간 혈청의 pH는 7.4인 반면, 평균 세포내 pH는 약 7.1~7.3 범위로, 약간 더 낮다. 엔도좀은 5.5~6.0의 범위의 더 산성인 pH를 가지며, 리소좀은 약 5.0의 훨씬 더 산성인 pH를 갖는다. 일부 링커는 바람직한 pH에서 절단되는 절단성 기를 가질 것이며, 이로써 세포 내부의 리간드로부터 또는 세포의 원하는 구획으로 RNA 분자를 방출할 수 있다.
링커는 특정 효소에 의해 절단될 수 있는 절단성 기를 포함할 수 있다. 링커에 포함된 절단성 기의 유형은 표적화될 세포에 의존할 수 있다. 예를 들어, 간-표적 리간드는 에스테르기를 포함하는 링커를 통해 RNA 분자에 연결될 수 있다. 간 세포는 에스테라제가 풍부하기 때문에, 링커는 에스테라제가 풍부하지 않은 세포 유형에서보다 간 세포에서 보다 효율적으로 절단될 것이다. 에스테라아제가 풍부한 다른 유형의 세포는 폐, 신장 피질 및 고환의 세포를 포함한다. 펩타이드 결합을 함유하는 링커는 간 세포 및 활막세포와 같은 펩티다아제가 풍부한 세포를 표적화할 때 사용될 수 있다.
일반적으로, 후보 절단성 링커의 적합성은 후보 링커를 절단하는 분해제(또는 조건)의 능력을 테스트함으로써 평가될 수 있다. 또한 혈액에서 또는 다른 비-표적 조직과 접촉할 때 절단에 저항하는 능력에 대해 후보 절단성 링커를 시험하는 것이 바람직할 것이다. 따라서, 제1 조건과 제2 조건 사이의 절단에 대한 상대적 민감성을 결정할 수 있으며, 여기서 첫 번째 조건은 표적 세포에서 절단을 나타내는 것으로 선택되고, 두 번째는 다른 조직 또는 생물학적 유체, 예를 들어 혈액 또는 혈청에서의 절단을 나타내는 것으로 선택된다. 평가는 무 세포 시스템, 세포, 세포 배양, 기관 또는 조직 배양, 또는 전체 동물에서 수행될 수 있다. 무 세포 또는 배양 조건에서 초기 평가를 수행하고 전체 동물에서 추가 평가를 통해 확인하는 것이 유용할 수 있다. 일부 구현예에서, 유용한 후보 링커는 혈액 또는 혈청과 비교하여 (또는 세포외 조건을 모방하도록 선택된 시험관내 조건 하에서) 세포에서(또는 세포내 조건을 모방하도록 선택된 시험관내 조건 하에서) 적어도 2, 4, 10, 20, 50, 70, 또는 100배 더 빨리 절단된다.
다른 구현예에서, 산화환원 절단성 링커가 사용된다. 산화환원 절단성 링커는 환원 또는 산화시 절단된다. 환원성 절단기의 예는 이황화 연결기(-S-S-)이다. 후보 절단성 링커가 적합한 "환원적으로 절단성 링커,"인지, 또는 예를 들어 특정 RNAi 작제물 및 특정 리간드와 함께 사용하기에 적합한지를 결정하기 위해, 본원에 기재된 하나 이상의 방법을 사용할 수 있다. 예를 들어, 후보 링커는 디티오트레이톨 (DTT), 또는 당업계에 공지된 다른 환원제와의 인큐베이션에 의해 평가될 수 있으며, 이는 세포, 예를 들어 표적 세포에서 관찰될 절단 속도를 모방한다. 후보 링커는 또한 혈액 또는 혈청 조건을 모방하도록 선택된 조건 하에서 평가될 수 있다. 특정 구현예에서, 후보 링커는 혈액에서 최대 10%까지 절단된다. 다른 구현예에서, 유용한 후보 링커는 혈액과 비교하여 (또는 세포외 조건을 모방하도록 선택된 시험관내 조건 하에서) 세포에서(또는 세포내 조건을 모방하도록 선택된 시험관내 조건 하에서) 적어도 2, 4, 10, 20, 50, 70, 또는 100배 더 빨리 분해된다.
또 다른 구현예에서, 포스페이트기를 분해하거나 가수분해하는 작용제에 의해 절단되는 포스페이트 기반의 절단성 링커가 RNAi 작제물의 센스 또는 안티센스 가닥에 리간드를 공유적으로 부착시키는 데 이용된다. 세포에서 포스페이트기를 가수분해하는 작용제의 예는 세포에서 포스파타제와 같은 효소이다. 포스페이트-기반 절단성 기의 예는 -O-P(O)(ORk)-O-, -O-P(S)(ORk)-O-, -O-P(S)(SRk)-O-, -S-P(O)(ORk)-O-, -O-P(O)(ORk)-S-, -S-P(O)(ORk)-S-, -O-P(S)(ORk)-S-, -S-P(S)(ORk)-O-, -O-P(O)(Rk)-O-, -O-P(S)(Rk)-O-, -S-P(O)(Rk)-O-, -S-P(S)(Rk)-O-, -S-P(O)(Rk)-S-, 및 -O-P(S)(Rk)-S-이고, 여기서 Rk는 수소 또는 C1-C10 알킬일 수 있다. 특정 구현예는 -O-P(O)(OH)-O-, -O-P(S)(OH)-O-, -O-P(S)(SH)-O-, -S-P(O)(OH)-O-, -O-P(O)(OH)-S-, -S-P(O)(OH)-S-, -O-P(S)(OH)-S-, -S-P(S)(OH)-O-, -O-P(O)(H)-O-, -O-P(S)(H)-O-, -S-P(O)(H)-O-, -S-P(S)(H)-O-, -S-P(O)(H)-S-, 및 -O-P(S)(H)-S-를 포함한다. 다른 특정 구현예는 -O-P(O)(OH)-O-이다. 이들 후보 링커는 상기 기술된 것과 유사한 방법을 사용하여 평가될 수 있다.
다른 구현예에서, 링커는 산성 조건 하에서 절단되는 기인, 산 절단성 기를 포함할 수 있다. 일부 구현예에서, 산 절단성 기는 pH가 약 6.5 이하(예를 들어, 약 6.0, 5.5, 5.0 이하)인 산성 환경에서, 또는 일반적인 산으로서 작용할 수 있는 효소와 같은 작용제에 의해 절단된다. 세포에서, 엔도좀 및 리소좀과 같은 특정 저 pH 소기관은 산 절단성 기에 대한 절단 환경을 제공할 수 있다. 산 절단성 연결기의 예는 히드라존, 에스테르 및 아미노산의 에스테르를 포함하지만, 이에 제한되지 않는다. 산 절단성 기는 일반 화학식 -C=NN-, C(O)O, 또는 -OC(O)를 가질 수 있다. 특정 구현예는 에스테르(알콕시 기)의 산소에 부착된 탄소가 아릴 기, 치환된 알킬기 또는 3차 알킬기, 예컨대 디메틸, 펜틸 또는 t-부틸인 경우이다. 이들 후보는 상기 기술된 것과 유사한 방법을 사용하여 평가될 수 있다.
다른 구현예에서, 링커는 에스테르-기반 절단성 기를 포함할 수 있으며, 이는 효소, 예컨대 세포에서 에스테라제 및 아미다제에 의해 절단된다. 에스테르-기반 절단성 기의 예는 알킬렌, 알케닐렌 및 알키닐렌 기의 에스테르를 포함하지만, 이에 제한되지 않는다. 에스테르 절단성 기는 일반 화학식 -C(O)O-, 또는 -OC(O)-를 가진다. 이들 후보 링커는 상기 기술된 것과 유사한 방법을 사용하여 평가될 수 있다.
추가 구현예에서, 링커는 에스테르-기반 절단성 기를 포함할 수 있으며, 이는 세포에서 효소, 예컨대 펩티다제 및 프로테아제에 의해 절단된다. 펩타이드-기반 절단성 기는 아미노산 사이에 형성되어 올리고펩타이드(예를 들어, 디펩타이드, 트리펩타이드 등) 및 폴리펩타이드를 생성하는 펩타이드 결합이다. 펩타이드-기반 절단성 기는 아미드 기(-C(O)NH-)를 포함한다. 아미드 기는 임의의 알킬렌, 알케닐렌 또는 알키닐렌 사이에서 형성될 수 있다. 펩타이드 결합은 아미노산 사이에 형성된 특별한 유형의 아미드 결합이며, 펩타이드 및 단백질을 생성한다. 펩타이드 기반 절단 기는 일반적으로 아미노산 사이에서 형성되어 펩타이드 및 단백질을 형성하는 펩타이드 결합(즉, 아미드 결합)에 제한된다. 펩타이드-기반 절단성 연결기는 일반 화학식 -NHCHRAC(O)NHCHRBC(O)-을 가지며, 여기서 RA 및 RB는 2개의 인접한 아미노산의 측쇄이다. 이들 후보는 상기 기술된 것과 유사한 방법을 사용하여 평가될 수 있다.
본 발명의 RNAi 작제물에서 센스 또는 안티센스 가닥에 리간드를 부착하기에 적합한 다른 유형의 링커는 당업계에 공지되어 있으며, 미국 특허 제7,723,509호; 제8,017,762호; 제8,828,956호; 제8,877,917호; 및 제9,181,551호에 기재되어 있는 링커를 포함할 수 있으며, 이들 모두는 그 전문이 본원에 참고로 포함된다.
특정 구현예에서, 본 발명의 RNAi 작제물의 센스 또는 안티센스 가닥에 공유적으로 부착된 리간드는 GalNAc 모이어티, 예를 들어 다가 GalNAc 모이어티를 포함한다. 일부 구현예에서, 다가 GalNAc 모이어티는 3가 GalNAc 모이어티이며, 센스 가닥의 3' 말단에 부착된다. 다른 구현예에서, 다가 GalNAc 모이어티는 3가 GalNAc 모이어티이며, 센스 가닥의 5' 말단에 부착된다. 또 다른 구현예에서, 다가 GalNAc 모이어티는 4가 GalNAc 모이어티이며, 센스 가닥의 3' 말단에 부착된다. 또 다른 구현예에서, 다가 GalNAc 모이어티는 4가 GalNAc 모이어티이며, 센스 가닥의 5' 말단에 부착된다.
특정 구현예에서, 본 발명의 RNAi 작제물은 다음의 구조([구조 1])를 갖는 리간드를 포함한다:
Figure pct00001
바람직한 구현예에서, 이 구조를 갖는 리간드는 링커, 예컨대, 본원에 기술된 링커를 통해 센스 가닥의 5' 말단(예를 들어 센스 가닥의 5' 말단 뉴클레오티드)에 공유적으로 부착된다. 일 구현예에서, 링커는 아미노헥실 링커이다.
본 발명의 RNAi 작제물의 이중 가닥 RNA 분자에 부착될 수 있는 예시적인 3가 및 4가 GalNAc 모이어티 및 링커는 아래의 구조식 I 내지 IX에 제공된다. 본원에 열거된 식에서 "Ac"는 아세틸기를 나타낸다.
일 구현예에서, RNAi 작제물은 다음의 화학식 I의 구조를 갖는 리간드 및 링커를 포함하고, 식에서 각각의 n은 독립적으로 1 내지 3, k는 1 내지 3, m은 1 또는 2, j는 1 또는 2이고, 리간드는 (물결 모양의 실선으로 표시된) 이중 가닥의 RNA 분자의 센스 가닥의 3' 말단에 부착된다:
[화학식 I]
Figure pct00002
다른 구현예에서, RNAi 작제물은 다음의 화학식 II의 구조를 갖는 리간드 및 링커를 포함하고, 식에서 각각의 n은 독립적으로 1 내지 3, k는 1 내지 3, m은 1 또는 2, j는 1 또는 2이고, 리간드는 (물결 모양의 실선으로 표시된) 이중 가닥의 RNA 분자의 센스 가닥의 3' 말단에 부착된다:
[화학식 II]
Figure pct00003
또 다른 구현예에서, RNAi 작제물은 다음의 화학식 III의 구조를 갖는 리간드 및 링커를 포함하고, 리간드는 (물결 모양의 실선으로 표시된) 이중 가닥의 RNA 분자의 센스 가닥의 3' 말단에 부착된다:
[화학식 III]
Figure pct00004
또 다른 구현예에서, RNAi 작제물은 다음의 화학식 IV의 구조를 갖는 리간드 및 링커를 포함하고, 리간드는 (물결 모양의 실선으로 표시된) 이중 가닥의 RNA 분자의 센스 가닥의 3' 말단에 부착된다:
[화학식 IV]
Figure pct00005
특정 구현예에서, RNAi 작제물은 다음의 화학식 V의 구조를 갖는 리간드 및 링커를 포함하고, 식에서 각각의 n은 독립적으로 1 내지 3, k는 1 내지 3이고, 리간드는 (물결 모양의 실선으로 표시된) 이중 가닥의 RNA 분자의 센스 가닥의 5' 말단에 부착된다:
[화학식 V]
Figure pct00006
다른 구현예에서, RNAi 작제물은 다음의 화학식 VI의 구조를 갖는 리간드 및 링커를 포함하고, 식에서 각각의 n은 독립적으로 1 내지 3, k는 1 내지 3이고, 리간드는 (물결 모양의 실선으로 표시된) 이중 가닥의 RNA 분자의 센스 가닥의 5' 말단에 부착된다:
[화학식 VI]
Figure pct00007
일 특정 구현예에서, RNAi 작제물은 다음의 화학식 VII의 구조를 갖는 리간드 및 링커를 포함하고, 식에서 X = O 또는 S이고, 리간드는 (구불구불한 선으로 표시된) 이중 가닥의 RNA 분자의 센스 가닥의 5' 말단에 부착된다:
[화학식 VII]
Figure pct00008
일부 구현예에서, RNAi 작제물은 다음의 화학식 VIII의 구조를 갖는 리간드 및 링커를 포함하고, 식에서 각각의 n은 독립적으로 1 내지 3이고, 리간드는 (물결 모양의 실선으로 표시된) 이중 가닥의 RNA 분자의 센스 가닥의 5' 말단에 부착된다:
[화학식 VIII]
Figure pct00009
특정 구현예에서, RNAi 작제물은 다음의 화학식 IX의 구조를 갖는 리간드 및 링커를 포함하고, 리간드는 (물결 모양의 실선으로 표시된) 이중 가닥의 RNA 분자의 센스 가닥의 5' 말단에 부착된다:
[화학식 IX]
Figure pct00010
포스포로티오에이트 결합은 화학식 I 내지 IX 중 임의의 하나에 제시된 포스포디에스테르 결합을 대신하여 리간드 및 링커를 핵산 가닥에 공유적으로 연결할 수 있다.
본 발명은 또한 본원에 기술된 RNAi 작제물 및 약제학적으로 허용가능한 담체, 부형제 또는 희석제를 포함하는 약제학적 조성물 및 제형을 포함한다. 이러한 조성물 및 제형은 이를 필요로 하는 환자에서 MARC1 유전자의 발현을 감소시키는 데 유용하다. 임상적 적용이 고려되는 경우, 약제학적 조성물 및 제형은 의도한 적용에 적절한 형태로 제조될 수 있다. 일반적으로, 이것은 본질적으로 발열원뿐만 아니라 인간 또는 동물에게 해로울 수 있는 다른 불순물이 없는 조성물의 제조를 수반할 것이다.
"약제학적으로 허용가능한" 또는 "약리학적으로 허용가능한"이란 어구는 동물 또는 인간에게 투여될 때 이상 반응, 알러지 반응, 또는 기타 부작용을 일으키지 않는 분자 물질 및 조성물을 지칭한다. 본원에서 사용되는 바와 같이, "약제학적으로 허용가능한 담체, 부형제 또는 희석제"는 약제, 예컨대 인간에게 투여하기에 적합한 약제를 제형화하는데 사용하는데 허용가능한 용매, 완충제, 용액, 분산 매질, 코팅제, 항균제 및 항진균제, 등장제 및 흡수 지연제 등을 포함한다. 약제학적으로 활성인 물질을 위한 이러한 매질 및 작용제의 사용은 당업계에 잘 알려져 있다. 임의의 통상적인 매질 또는 작용제가 본 발명의 RNAi 작제물과 불상용성인 경우를 제외하고, 치료적 조성물에서의 이의 사용이 고려된다. 보충 활성 성분은 또한 조성물의 RNAi 작제물을 불활성화시키지 않는다면 조성물에 혼입될 수 있다.
약제학적 조성물의 제형화를 위한 조성물 및 방법은 투여 경로, 치료될 질환 또는 장애의 유형 및 정도, 또는 투여량을 포함하지만 이에 제한되지 않는 다수의 기준에 의존한다. 일부 구현예에서, 약제학적 조성물은 의도된 전달 경로에 기초하여 제형화된다. 예를 들어, 특정 구현예에서, 약제학적 조성물은 비경구 전달용으로 제형화된다. 비경구 전달 형태는 정맥 내, 동맥 내, 피하, 척수강 내, 복강 내 또는 근육 내 주사 또는 주입을 포함한다. 일 구현예에서, 약제학적 조성물은 정맥 내 전달용으로 제형화된다. 이러한 구현예에서, 약제학적 조성물은 지질-계 전달 비히클을 포함할 수 있다. 다른 구현예에서, 약제학적 조성물은 피하 전달용으로 제형화된다. 이러한 구현예에서, 약제학적 조성물은 표적화 리간드(예를 들어, 본원에 기재된 GalNAc 함유 또는 항체 함유 리간드)를 포함할 수 있다.
일부 구현예에서, 약제학적 조성물은 본원에 기재된 유효량의 RNAi 작제물을 포함한다. "유효량"은 유익하거나 바람직한 임상 결과를 생성하기에 충분한 양이다. 일부 구현예에서, 유효량은 환자의 특정 조직 또는 세포 유형(예를 들어, 간 또는 간세포)에서 MARC1 유전자 발현을 감소시키기에 충분한 양이다. 본 발명의 RNAi 작제물의 유효량은 약 0.01 mg/kg(체중) 내지 약 100 mg/kg(체중)일 수 있고, 매일, 매주, 매달, 또는 더 긴 간격으로 투여될 수 있다. 유효한 양 및 투여 빈도로 간주되는 것의 정확한 결정은 환자의 크기, 연령 및 일반적인 상태, 치료될 장애의 유형(예를 들어 지방간 질환, 간 섬유증, 또는 심혈관 질환), 사용된 특정 RNAi 작제물 및 투여 경로를 비롯한 여러 요인에 기초할 수 있다.
본 발명의 약제학적 조성물의 투여는 표적 조직이 상기 경로를 통해 이용 가능한한 임의의 공통 경로를 통해 이루어질 수 있다. 이러한 경로는 비경구(예를 들어, 피하, 근육 내, 복강 내 또는 정맥 내), 경구, 비강, 협측, 피내, 경피 및 설하 경로, 또는 간 조직으로의 직접 주사 또는 간문맥을 통한 전달을 포함하지만, 이에 제한되지는 않는다. 일부 구현예에서, 약제학적 조성물은 비경구 투여된다. 예를 들어, 특정 구현예에서, 약제학적 조성물은 정맥 내 투여된다. 다른 구현예에서, 약제학적 조성물은 피하 투여된다.
콜로이드 분산 시스템, 예컨대 거대 분자 복합체, 나노캡슐, 마이크로스피어, 비드 및 수중유 에멀젼, 미셀, 혼합 미셀 및 리포좀을 포함한 지질-기반 시스템이 본 발명의 RNAi 작제물의 전달 비히클로서 사용될 수 있다. 본 발명의 핵산의 전달에 적합한, 상업적으로 이용 가능한 지방 에멀젼은 Intralipid®(Baxter International Inc.), Liposyn®(Abbott Pharmaceuticals), Liposyn®II(Hospira), Liposyn®III(Hospira), Nutrilipid(B. Braun Medical Inc.), 및 기타 유사한 지질 에멀젼을 포함한다. 생체내에서 전달 비히클로서 사용하기 위한 예시적인 콜로이드 시스템은 리포좀(즉, 인공 막 비히클)이다. 본 발명의 RNAi 작제물은 리포좀 내에 캡슐화될 수 있거나, 또는 리포좀, 특히 양이온성 리포좀과 복합체를 형성할 수 있다. 대안적으로, 본 발명의 RNAi 작제물은 지질, 특히 양이온성 지질에 복합체화될 수 있다. 적합한 지질 및 리포좀은 중성(예를 들어, 디올레오일포스파티딜 에탄올아민(DOPE), 디미리스토일포스파티딜 콜린(DMPC), 및 디팔미토일 포스파티딜콜린(DPPC)), 디스테아로일포스파티딜 콜린), 음성(예를 들어, 디미리스토일포스파티딜 글리세롤(DMPG)), 및 양이온성(예를 들어, 디올레오일테트라메틸아미노프로필(DOTAP) 및 디올레오일포스파티딜 에탄올아민(DOTMA))을 포함한다. 이러한 콜로이드 분산 시스템의 제조 및 사용은 당업계에 잘 알려져 있다. 예시적인 제형은 또한 미국 특허 제5,981,505호; 미국 특허 제6,217,900호; 미국 특허 제6,383,512호; 미국 특허 제5,783,565호; 미국 특허 제7,202,227호; 미국 특허 제6,379,965호; 미국 특허 제6,127,170호; 미국 특허 제5,837,533호; 미국 특허 제6,747,014호; 및 WIPO 공개 번호 W003/093449에 개시되어 있다.
일부 구현예에서, 본 발명의 RNAi 작제물은 예를 들어, SNALP 또는 다른 핵산-지질 입자를 형성하기 위해 지질 제형으로 완전히 캡슐화된다. 본원에서 사용되는 바와 같이, 용어 "SNALP"는 안정한 핵산-지질 입자를 지칭한다. SNALP는 일반적으로 양이온성 지질, 비 양이온성 지질, 및 입자의 응집을 방지하는 지질(예를 들어, PEG-지질 접합체)을 함유한다. SNALP는 정맥 주사 후 연장된 순환 수명을 나타내고 말단 부위(예를 들어, 투여 부위와 물리적으로 분리된 부위)에 축적되기 때문에 전신 적용에 매우 유용하다. 핵산-지질 입자는 전형적으로 약 50 nm 내지 약 150 nm, 약 60 nm 내지 약 130 nm, 약 70 nm 내지 약 110 nm, 또는 약 70 nm 내지 약 90 nm의 평균 직경을 가지며, 실질적으로 비독성이다. 또한, 핵산-지질 입자에 존재할 때 핵산은 수용액에서 뉴클레아제에 의한 분해에 내성이 있다. 핵산-지질 입자 및 이의 제조 방법은 예를 들어, 미국 특허 제5,976,567호; 제5,981,501호; 제6,534,484호; 제6,586,410호; 제6,815,432호; 및 WIPO 공개 번호 WO96/40964에 개시되어 있다.
주사용으로 적합한 약제학적 조성물은 예를 들어, 멸균 수용액 또는 분산액 그리고 멸균 주사용 용액 또는 분산액의 즉석 제조를 위한 멸균 분말을 포함한다. 일반적으로, 이들 제제는 용이한 주사 가능성이 존재하는 정도로 멸균되고 유동적이다. 제제는 제조 및 저장 조건 하에서 안정하여야 하고, 박테리아 및 진균과 같은 미생물의 오염 작용으로부터 보존되어야 한다. 적당한 용매 또는 분산 매질은 예를 들어, 물, 에탄올, 폴리올(예를 들어, 글리세롤, 프로필렌 글리콜 및 액체 폴리에틸렌 글리콜 등), 이들의 적합한 혼합물 및 식물성 오일을 함유할 수 있다. 적절한 유동성은, 예를 들어, 레시틴과 같은 코팅의 사용에 의해, 분산물의 경우에 필요한 입자 크기의 유지에 의해, 그리고 계면활성제의 사용에 의해 유지될 수 있다. 미생물의 작용의 방지는 다양한 항균제 및 항진균제, 예를 들어, 파라벤, 클로로부탄올, 페놀, 소르빈산, 티메로살 등에 의해 초래될 수 있다. 많은 경우에, 등장화제, 예를 들어, 당 또는 염화나트륨을 포함하는 것이 바람직할 것이다. 주사 가능한 조성물의 지연된 흡수는 조성물 중 흡수를 지연시키는 작용제, 예를 들어, 알루미늄 모노스테아레이트 및 젤라틴의 사용에 의해 초래될 수 있다.
멸균 주사용 용액은 원하는 양의 임의의 다른 성분과 함께(예를 들어 상기 열거한 바와 같이) 적절한 양의 활성 화합물을 용매에 혼입시킨 후 여과 멸균함으로써 제조할 수 있다. 일반적으로, 분산액은 염기성 분산 매질 및 예를 들어, 위에 열거된 것들로부터 원하는 다른 성분을 함유하는 살균 비히클 내에 다양한 살균된 활성 성분을 포함시키는 것에 의해 제조된다. 살균 주사가능 용액의 제조를 위한 살균 분말의 경우에, 바람직한 제조 방법은 활성 성분(들)에 더하여 임의의 부가적인 요망되는 성분의 분말을 미리 살균-여과한 이의 용액으로부터 생산하는 진공-건조 및 동결-건조 기법을 포함한다.
본 발명의 조성물은 일반적으로 중성 또는 염 형태로 제형화될 수 있다. 약제학적으로 허용가능한 염은 예를 들어, 무기산(예를 들어, 염산 또는 인산) 또는 유기산(예를 들어, 아세트산, 옥살산, 타르타르산, 만델산 등)으로부터 유도된 산 부가 염(유리 아미노기로 형성됨)을 포함한다. 유리 카르복실기로 형성된 염은 또한 무기 염기(예를 들어, 나트륨, 칼륨, 암모늄, 칼슘, 또는 수산화 제2철)로부터 또는 유기 염기(예를 들어, 이소프로필아민, 트리메틸아민, 히스티딘, 프로카인 등)로부터 유래될 수 있다. 약제학적으로 허용가능한 염은 문헌[Berge et al., J. Pharmaceutical Sciences, Vol. 66: 1-19, 1977]에 상세히 기술되어 있다.
수용액에서의 비경구 투여를 위해, 예를 들어, 용액은 일반적으로 적절하게 완충되고, 액체 희석제는 먼저 예를 들어 충분한 식염수 또는 글루코스로 등장성이 된다. 이러한 수용액은 예를 들어, 정맥 내, 근육 내, 피하, 및 복강 내 투여에 사용될 수 있다. 바람직하게는, 특히 본 발명에 비추어 당업자에게 공지된 멸균 수성 매질이 사용된다. 예를 들어, 단일 용량을 등장성 NaCl 용액 1 ml에 용해시키고 1000 ml의 피하주사액에 첨가하거나, 제안된 주입 부위에 주사할 수 있다(예를 들어, "Remington's Pharmaceutical Sciences" 15th Edition, 페이지 1035-1038 및 1570-1580 참고). 인간 투여의 경우, 제제는 FDA 표준에서 요구하는 무균성, 발열성, 일반적인 안전 및 순도 표준을 충족해야 한다. 특정 구현예에서, 본 발명의 약제학적 조성물은 멸균 식염수 용액 및 본원에 기재된 RNAi 작제물을 포함하거나 이로 구성된다. 다른 구현예에서, 본 발명의 약제학적 조성물은 본원에 기재된 RNAi 작제물 및 멸균 수(예를 들어, 주사용수, WFI)를 포함하거나 이로 구성된다. 또 다른 구현예에서, 본 발명의 약제학적 조성물은 본원에 기재된 RNAi 작제물 및 포스페이트-완충 식염수(PBS)를 포함하거나 이로 구성된다.
일부 구현예에서, 본 발명의 약제학적 조성물은 투여용 장치와 함께 패키징되거나 그 안에 저장된다. 주사용 제형을 위한 장치는 주사 포트, 사전충전형 주사기, 자동 주사기, 주사 펌프, 체내 주사기 및 주사 펜을 포함하지만 이에 제한되지는 않는다. 에어로졸화 또는 분말 제형을 위한 장치는 흡입기, 취입기, 흡인기 등을 포함하지만 이에 제한되지는 않는다. 따라서, 본 발명은 본원에 기재된 하나 이상의 질환 또는 장애를 치료하거나 예방하기 위한 본 발명의 약제학적 조성물을 포함하는 투여 장치를 포함한다.
본 발명은 본원에 기재된 RNAi 작제물 중 임의의 하나와 세포(예를 들어, 간 세포)를 접촉시켜 세포에서 MARC1 유전자의 발현을 감소시키거나 억제하여 mARC1 단백질을 생성하는 방법을 제공한다. 세포는 시험관내 또는 생체내에 있을 수 있다. mARC1 발현은 mARC1 mRNA, mARC1 단백질, 또는 mARC1 발현에 연결된 다른 바이오마커의 양 또는 수준, 예컨대 콜레스테롤, LDL 콜레스테롤, 또는 간 효소(예컨대 알라닌 아미노전이효소(ALT))의 혈청 수준을 측정함으로써 평가될 수 있다. 본 발명의 RNAi 작제물로 처리된 세포 또는 동물에서 mARC1 발현의 감소는 RNAi 작제물로 처리되지 않거나 대조군 RNAi 작제물로 처리된 세포 또는 동물에서의 mARC1 발현과 관련하여 결정될 수 있다. 예를 들어, 일부 구현예에서, mARC1 발현의 감소는 (a) 본 발명의 RNAi 작제물로 처리된 간 세포에서 mARC1 mRNA의 양 또는 수준을 측정하고, (b) 대조군 RNAi 작제물(예를 들어, 간 세포에서 발현되지 않는 RNA 분자를 지향하는 RNAi 작제물 또는 논센스 또는 스크램블링된 서열을 갖는 RNAi 작제물)로 처리된 또는 작제물이 없는 간 세포내 mARC1 mRNA의 양 또는 수준을 측정하고, 및 (c) (a)에서의 처리된 세포로부터 측정된 mARC1 mRNA 수준을 (b)에서의 대조군 세포로부터 측정된 mARC1 mRNA 수준과 비교함으로써 평가된다. 처리된 세포 및 대조군 세포에서의 mARC1 mRNA 수준은 비교 전에 대조군 유전자(예를 들어 18S 리보솜 RNA 또는 하우스키핑 유전자)에 대한 RNA 수준으로 정규화될 수 있다. mARC1 mRNA 수준은 노던 블롯 분석, 뉴클레아제 보호 분석, 형광동소보합법(FISH), 역전사 효소(RT)-PCR, 실시간 RT-PCR, 정량적 PCR, 미세방울 디지털 PCR 등을 포함하는 다양한 방법으로 측정될 수 있다.
다른 구현예에서, mARC1 발현의 감소는 (a) 본 발명의 RNAi 작제물로 처리된 간 세포에서 mARC1 단백질의 양 또는 수준을 측정하고, (b) 대조군 RNAi 작제물(예를 들어, 간 세포에서 발현되지 않는 RNA 분자를 지향하는 RNAi 작제물 또는 논센스 또는 스크램블링된 서열을 갖는 RNAi 작제물)로 처리된 또는 작제물이 없는 간 세포내 mARC1 단백질의 양 또는 수준을 측정하고, 및 (c) (a)에서의 처리된 세포로부터 측정된 mARC1 단백질 수준을 (b)에서의 대조군 세포로부터 측정된 mARC1 단백질 수준과 비교함으로써 평가된다. mARC1 단백질 수준을 측정하는 방법은 당업자에게 공지되어 있으며, 웨스턴 블롯, 면역 분석(예를 들어, ELISA), 및 유세포 분석을 포함한다. mARC1 mRNA 또는 mARC1 단백질을 측정할 수 있는 임의의 방법을 사용하여 본 발명의 RNAi 작제물의 효능을 평가할 수 있다.
일부 구현예에서, mARC1 발현 수준을 평가하는 방법은 mARC1를 본래 발현하는 세포(예를 들어, 간 세포) 또는 mARC1을 발현하도록 조작된 세포에서 시험관 내에서 수행된다. 특정 구현예에서, 방법은 간 세포에서 시험관내 수행된다. 적합한 간 세포는 1차 간세포(예를 들어, 인간 또는 비-인간 영장류 간세포), HepAD38 세포, HuH-6 세포, HuH-7 세포, HuH-5-2 세포, BNLCL2 세포, Hep3B 세포, 또는 HepG2 세포를 포함하지만, 이에 제한되지 않는다. 일 구현예에서, 간 세포는 HuH-7 세포이다. 다른 구현예에서, 간 세포는 인간 1차 간세포이다. 또 다른 구현예에서, 간 세포는 Hep3B 세포이다.
다른 구현예에서, mARC1 발현 수준을 평가하는 방법은 생체내에서 수행된다. RNAi 작제물 및 임의의 대조군 RNAi 작제물은 동물에 치료 후 동물로부터 수확된 간 조직에서 평가된 mARC1 mRNA 또는 mARC1 단백질 수준으로 투여될 수 있다. 대안적으로 또는 추가적으로, mARC1 발현과 관련된 바이오마커 또는 기능적 표현형은 처리된 동물에서 평가될 수 있다. 예를 들어, MARC1 기능손실 변이체는 혈청 총 콜레스테롤, LDL 콜레스테롤, 및 간 효소 수준의 감소와 관련이 있다(Emdin et al., PLoS Genet, Vol. 16(4): e1008629, 2020 참조). 따라서, 콜레스테롤, LDL 콜레스테롤, 또는 간 효소(예를 들어, ALT)의 혈청 또는 혈장 수준은 mARC1 발현 감소의 기능적 효능을 평가하기 위해 본 발명의 RNAi 작제물로 처리된 동물에서 측정될 수 있다. 혈청 또는 혈장 콜레스테롤 또는 효소 수준을 측정하기 위한 예시적인 방법은 실시예 1, 4, 및 5에 기술되어 있다.
특정 구현예에서, mARC1 mRNA 또는 단백질의 발현은 간 세포에서 본 발명의 RNAi 작제물에 의해 적어도 40%, 적어도 45%, 또는 적어도 50% 만큼 감소된다. 일부 구현예에서, mARC1 mRNA 또는 단백질의 발현은 간 세포에서 본 발명의 RNAi 작제물에 의해 적어도 60%, 적어도 65%, 적어도 70%, 적어도 75%, 적어도 80%, 또는 적어도 85% 만큼 감소된다. 다른 구현예에서, mARC1 mRNA 또는 단백질의 발현은 간 세포에서 본 발명의 RNAi 작제물에 의해 약 90% 또는 그 이상, 예를 들어, 91%, 92%, 93%, 94%, 95%, 96%,97%, 98%, 99%, 또는 그 이상만큼 감소된다. mARC1 발현의 감소 백분율은 본원에 기재된 임의의 방법뿐만 아니라 당업계에 공지된 다른 방법에 의해 측정될 수 있다.
본 발명은 mARC1 발현 또는 활성과 관련된 병태, 질환 또는 장애를 치료 또는 예방하는 방법뿐만 아니라 이를 필요로 하는 환자에서 MARC1 유전자의 발현을 감소시키거나 억제하여 mARC1 단백질을 생성하는 방법을 제공한다. "mARC1 발현과 관련된 병태, 질환 또는 장애"는 mARC1 발현 수준이 변경되거나 mARC1의 증가된 발현 수준이 병태, 질환 또는 장애의 발병 위험 증가와 관련된 병태, 질환, 또는 장애를 지칭한다. mARC1 발현과 관련된 병태, 질환, 또는 장애는 또한 콜레스테롤, 지질, 트리글리세리드 등의 비정상적이거나 상승된 수준 또는 이들 분자의 손상된 클리어런스를 야기하는 변화와 같은 지단백질 대사의 비정상적인 변화로 인한 병태, 질환, 또는 장애를 포함한다. 최근의 유전 연구에서는 MARC1 유전자의 기능상실 변이체와 콜레스테롤 및 간 효소의 혈중 수준 감소, 간 지방 감소, 및 간경변으로부터의 보호 사이의 연관성이 보고되었다(문헌[Spracklen et al., Hum Mol Genet., Vol. 26(9):1770-178, 2017; Emdin et al., bioRxiv 594523; //doi.org/10.1101/594523, 2019; 및 Emdin et al., PLoS Genet, Vol. 16(4): e1008629, 2020)]). 문헌[Emdin et al., bioRxiv 594523; //doi.org/10.1101/594523, 2019; and Emdin et al., PLoS Genet, Vol. 16(4): e1008629, 2020)] 참조. 따라서, 특정 구현예에서, 본 발명의 RNAi 작제물은 간 섬유증 및 혈청 콜레스테롤 수준을 감소시킬 뿐만 아니라 지방간 질환(예를 들어 NAFLD 및 NASH) 및 심혈관 질환(예를 들어 관상 동맥 질환 및 심근 경색증)을 치료 또는 예방하는 데 특히 유용하다.
본 발명의 방법에 따라 치료 또는 예방될 수 있는 mARC1 발현과 관련된 병태, 질환, 및 장애에는 지방간 질환(예컨대 알코올성 지방간 질환, 알코올성 지방간염, NAFLD 및 NASH); 만성 간질환; 간경변; 심혈관 질환(예컨대 심근경색, 심부전, 뇌졸중(허혈성 및 출혈성), 죽상동맥경화증, 관상동맥질환, 말초혈관질환(예를 들어 말초동맥질환), 뇌혈관질환, 취약 플라크, 및 대동맥 판막 협착증); 가족성 고콜레스테롤혈증; 정맥 혈전증; 고콜레스테롤혈증; 고지혈증; 및 이상지질혈증(예를 들면, 총 콜레스테롤 상승, 저밀도 지단백질(LDL) 상승, 초저밀도 지단백질(VLDL) 상승, 트리글리세리드 상승, 및/또는 낮은 수준의 고밀도 지단백질(HDL)로서 나타남)을 포함하지만, 이에 제한되지 않는다.
특정 구현예에서, 본 발명은 본원에 기재된 임의의 RNAi 작제물을 mARC1 단백질 발현의 감소를 필요로 하는 환자에게 투여하는 단계를 포함하는, 환자의 mARC1 단백질의 발현을 감소시키는 방법을 제공한다. 용어 "환자"는, 본원에서 사용되는 바와 같이, 인간을 포함하는 포유동물을 지칭하고, 용어 "대상체"와 상호교환적으로 사용될 수 있다. 바람직하게는, 환자의 간세포에서 mARC1의 발현 수준은 RNAi 작제물을 투여받지 않은 환자에서의 mARC1 발현 수준 또는 RNAi 작제물의 투여 전 환자의 mARC1 발현 수준에 비해 RNAi 작제물의 투여 후 감소된다. 일부 구현예에서, 본 발명의 RNAi 작제물의 투여 후, mARC1의 발현은 환자에서 적어도 30%, 적어도 35%, 적어도 40%, 적어도 45%, 적어도 50%, 적어도 55%, 적어도 60%, 적어도 65%, 적어도 70%, 적어도 75%, 적어도 80%, 적어도 85%, 또는 적어도 90%, 예를 들어, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 만큼 감소한다. mARC1 발현의 감소 백분율은 본원에 기재된 임의의 방법뿐만 아니라 당업계에 공지된 다른 방법에 의해 측정될 수 있다. 특정 구현예에서, mARC1 발현의 백분율 감소는 본원에 기재된 방법에 따라 환자에서 총 콜레스테롤, LDL 콜레스테롤, 또는 간 효소(예를 들어 ALT) 수준과 같은 혈청 또는 혈장 바이오마커의 수준을 평가함으로써 확인된다.
일부 구현예에서, mARC1 발현의 감소가 필요한 환자는 심근 경색증을 가질 위험이 있는 환자이다. 심근 경색을 가질 위험이 있는 환자는 심근 경색의 병력(예를 들어 심근 경색을 이전에 앓았음)을 갖는 환자일 수 있다. 심근경색을 가질 위험이 있는 환자는 또한 심근경색의 가족력이 있거나 심근경색의 위험 인자가 하나 이상 있는 환자일 수 있다. 이러한 위험 인자에는 고혈압, 비-HDL 콜레스테롤 수준 상승, 트리글리세라이드 수준 상승, 당뇨병, 비만, 또는 자가면역 질환(예를 들어 류마티스 관절염, 루푸스) 병력이 포함되지만, 이에 제한되지 않는다. 일 구현예에서, 심근 경색증을 가질 위험이 있는 환자는 관상 동맥 질환이 있거나 이를 진단받은 환자이다. 이들 및 다른 환자에서 심근 경색의 위험은 본원에 기재된 임의의 RNAi 작제물을 환자에게 투여함으로써 감소될 수 있다. 따라서, 본 발명은 본원에 기재된 RNAi 작제물을 환자에게 투여하는 단계를 포함하는, 심근 경색의 위험의 감소를 필요로 하는 환자에서 이를 감소시키는 방법을 제공한다. 일부 구현예에서, 본 발명은 심근 경색의 위험의 감소를 필요로 하는 환자에서 이를 위한 의약의 제조에 있어서 본원에 기재된 임의의 RNAi 작제물의 용도를 포함한다. 다른 구현예에서, 본 발명은 심근 경색의 위험의 감소를 필요로 하는 환자에서 이를 감소시키는 방법에 사용하기 위한 mARC1 표적 RNAi 작제물을 제공한다.
특정 구현예에서, mARC1 발현의 감소를 필요로 하는 환자는 심혈관 질환으로 진단되었거나 심혈관 질환의 위험이 있는 환자이다. 따라서, 본 발명은 본 발명의 임의의 RNAi 작제물을 투여함으로써 심혈관 질환의 치료 또는 예방을 필요로 하는 환자에서 이를 치료 또는 예방하는 방법을 포함한다. 일부 구현예에서, 본 발명은 심혈관 질환의 치료 또는 예방을 필요로 하는 환자에서 이를 치료 또는 예방하기 위한 의약의 제조에 있어서 본원에 기재된 임의의 RNAi 작제물의 용도를 포함한다. 다른 구현예에서, 본 발명은 심혈관 질환의 치료 또는 예방을 필요로 하는 환자에서 이를 치료 또는 예방하는 방법에 사용하기 위한 mARC1 표적 RNAi 작제물을 제공한다. 심혈관 질환에는 심근경색, 심부전, 뇌졸중(허혈성 및 출혈성), 죽상동맥경화증, 관상동맥질환, 말초혈관질환(예를 들어 말초동맥질환), 뇌혈관질환, 취약 플라크, 및 대동맥 판막 협착증을 포함하지만, 이에 제한되지 않는다. 일부 구현예에서, 본 발명의 방법에 따라 치료 또는 예방되는 심혈관 질환은 관상 동맥 질환이다. 다른 구현예에서, 본 발명의 방법에 따라 치료 또는 예방되는 심혈관 질환은 심근경색증이다. 또 다른 구현예에서, 본 발명의 방법에 따라 치료 또는 예방되는 심혈관 질환은 뇌졸중이다. 또 다른 구현예에서, 본 발명의 방법에 따라 치료 또는 예방되는 심혈관 질환은 말초동맥질환이다. 특정 구현예에서, 본원에 기재된 RNAi 작제물의 투여는 비치명적 심근경색증, 치명적 및 비치명적 뇌졸중, 특정 유형의 심장 수술(예를 들어 혈관성형술, 우회술), 심부전으로 인한 입원, 심장 질환이 있는 환자의 흉통, 및/또는 확립된 심장 질환이 있는 환자의 심혈관 사례(예를 들어 이전 심근 경색, 이전 심장 수술, 및/또는 막힌 동맥의 증거가 있는 흉통)의 위험을 감소시킨다. 일부 구현예에서, 본 발명의 방법에 따라 본원에 기재된 RNAi 작제물의 투여는 재발성 심혈관 사례의 위험을 감소시키는데 사용될 수 있다.
일부 구현예에서, 본 발명의 방법에 따라 치료되는 환자는 취약한 플라크(불안정 플라크라고도 함)가 있는 환자이다. 취약한 플라크는 동맥벽의 내피층 아래에 있는 콜레스테롤을 주로 포함하는 대식세포 및 지질의 축적이다. 이 취약한 플라크는 파열되어 혈전이 형성되어, 잠재적으로 동맥을 통한 혈류를 차단하고 심근 경색이나 뇌졸중을 일으킬 수 있다. 취약한 플라크는 당업계에 공지된 방법(혈관내 초음파 및 컴퓨터 단층촬영을 포함하지만, 이에 제한되지 않음)에 의해 확인될 수 있다(문헌[Sahara et al., European Heart Journal, Vol. 25: 2026-2033, 2004; Budhoff, J. Am. Coll. Cardiol., Vol. 48: 319-321, 2006; Hausleiter et al., J. Am. Coll. Cardiol., Vol. 48: 312-318, 2006] 참조).
다른 구현예에서, mARC1 발현의 감소를 필요로 하는 환자는 콜레스테롤(예를 들어 총 콜레스테롤, 비-HDL 콜레스테롤, 또는 LDL 콜레스테롤)의 혈중 수준이 상승된 환자이다. 따라서, 일부 구현예에서, 본 발명은 본원에 기재된 임의의 RNAi 작제물을 환자에게 투여하는 단계를 포함하는, 콜레스테롤의 혈중 수준(예를 들어 혈청 또는 혈장)의 감소를 필요로 하는 환자에서 이를 감소시키는 방법을 제공한다. 일부 구현예에서, 본 발명은 콜레스테롤의 혈중 수준(예를 들어 혈청 또는 혈장)의 감소를 필요로 하는 환자에서 이를 위한 의약의 제조에 있어서 본원에 기재된 임의의 RNAi 작제물의 용도를 포함한다. 다른 구현예에서, 본 발명은 콜레스테롤의 혈중 수준(예를 들어 혈청 또는 혈장)의 감소를 필요로 하는 환자에서 이를 감소시키는 방법에 사용하기 위한 mARC1 표적 RNAi 작제물을 제공한다. 특정 구현예에서, 본 발명의 방법에 따라 감소되는 콜레스테롤은 LDL 콜레스테롤이다. 다른 구현예에서, 본 발명의 방법에 따라 감소되는 콜레스테롤은 비-HDL 콜레스테롤이다. 비-HDL 콜레스테롤은 LDL 콜레스테롤, 초저밀도 지단백질, 중간 밀도 지단백질, 지단백질(a), 킬로미크론, 및 킬로미크론 잔재를 포함한 모든 콜레스테롤 함유 전동맥경화성 지단백질의 척도이다. 비-HDL 콜레스테롤은 심혈관 위험의 좋은 예측인자로 보고되었다(Rana et al., Curr. Atheroscler. Rep., Vol. 14:130-134, 2012). 비-HDL 콜레스테롤 수준은 총 콜레스테롤 수준에서 HDL 콜레스테롤 수준을 제하여 계산할 수 있다.
일부 구현예에서, 본 발명의 방법에 따라 치료되는 환자는 비-HDL 콜레스테롤 수준이 상승된(예를 들어 비-HDL 콜레스테롤의 혈청 또는 혈장 수준 상승) 환자이다. 이상적으로, 비-HDL 콜레스테롤 수준은 임의의 지정된 환자의 LDL 콜레스테롤 수준 목표치보다 약 30 mg/dL 높아야 한다. 특정 구현예에서, 환자의 비-HDL 콜레스테롤 수준이 약 130 mg/dL 이상인 경우, 환자에게 본 발명의 RNAi 작제물이 투여된다. 일 구현예에서, 환자의 비-HDL 콜레스테롤 수준이 약 160 mg/dL 이상인 경우, 환자에게 본 발명의 RNAi 작제물이 투여된다. 다른 구현예에서, 환자의 비-HDL 콜레스테롤 수준이 약 190 mg/dL 이상인 경우, 환자에게 본 발명의 RNAi 작제물이 투여된다. 또 다른 구현예에서, 환자의 비-HDL 콜레스테롤 수준이 약 220 mg/dL 이상인 경우, 환자에게 본 발명의 RNAi 작제물이 투여된다. 특정 구현예에서, 환자가 심혈관 위험 평가에 대한 2013 ACC/AHA 가이드라인(문헌[Goff et al., ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, Vol. 63:2935-2959, 2014])에 따라 심혈관 질환의 위험이 높거나 매우 높고, 비-HDL 콜레스테롤 수준이 약 100 mg/dL 이상인 경우 환자에게 본 발명의 RNAi 작제물이 투여된다.
본 발명의 방법의 특정 구현예에서, 환자가 심혈관 위험 평가에 대한 2013 ACC/AHA 가이드라인(본원에서는 "2013 가이드라인"이라고 함)에 따라 심혈관 질환에 대한 중간 위험 또는 그보다 높은 위험이 있는 경우, 환자에게 본원에 기재된 RNAi 작제물이 투여된다. 특정 구현예에서, 본 발명의 RNAi 작제물은 환자의 LDL 콜레스테롤 수준이 약 160 mg/dL를 초과하는 경우, 환자에게 투여된다. 다른 구현예에서, 본 발명의 RNAi 작제물은 환자의 LDL 콜레스테롤 수준이 약 130 mg/dL를 초과하고, 환자가 2013 가이드라인에 따라 심혈관 질환의 중등도 위험이 있는 경우, 환자에게 투여된다. 또 다른 구현예에서, 본 발명의 RNAi 작제물은 환자의 LDL 콜레스테롤 수준이 100 mg/dL를 초과하고, 환자가 2013 가이드라인에 따라 심혈관 질환의 위험이 높거나 매우 높은 경우, 환자에게 투여된다.
다른 구현예에서, mARC1 발현의 감소를 필요로 하는 환자는 지방간 질환으로 진단되었거나 지방간 질환의 위험이 있는 환자이다. 따라서, 본 발명은 환자에게 본 발명의 임의의 RNAi 작제물을 투여하는 단계를 포함하는, 지방간 질환의 치료, 예방, 또는 발병 위험의 감소를 필요로 하는 환자에서 이를 치료하거나, 예방하거나, 이의 발병 위험을 감소시키는 방법을 포함한다. 일부 구현예에서, 본 발명은 지방간 질환의 치료, 예방, 또는 발병 위험의 감소를 필요로 하는 환자에서 이를 위한 의약의 제조에 있어서 본원에 기재된 임의의 RNAi 작제물의 용도를 포함한다. 다른 구현예에서, 본 발명은 지방간 질환의 치료, 예방, 또는 발병 감소를 필요로 하는 환자에서 이의 방법에 사용하기 위한 mARC1 표적 RNAi 작제물을 제공한다. 지방간 질환은 간에 지방이 축적되는 병태이다. 지방간 질환에는 두 가지 주요 유형이 있다: 첫 번째 유형은 과도한 알코올 사용과 관련된 유형(알코올성 지방간염)이고 두 번째 유형은 알코올 사용과 무관하다(비알코올성 지방간 질환(NAFLD)). NAFLD는 일반적으로 간에 지방 축적이 있지만 염증이나 간 세포 손상이 거의 또는 전혀 없는 것이 특징이다. NAFLD는 간 염증 및 세포 손상을 특징으로 하는 비알코올성 지방간염(NASH)으로 진행될 수 있으며, 이 두 가지 모두 결과적으로 간 섬유증 및 종국에는 간경화 또는 간암으로 이어질 수 있다. 특정 구현예에서, 본 발명의 방법에 따라 치료, 예방, 또는 발병 위험을 감소시키는 지방간 질환은 NAFLD이다. 다른 구현예에서, 본 발명의 방법에 따라 치료, 예방, 또는 발병 위험을 감소시키는 지방간 질환은 NASH이다. 또 다른 구현예에서, 본 발명의 방법에 따라 치료, 예방, 또는 발병 위험을 감소시키는 지방간 질환은 알코올성 지방간염이다. 일부 구현예에서, 본 발명의 방법에 따라 지방간 질환에 대한 치료 또는 예방이 필요하거나 지방간 질환이 발병할 위험이 있는 환자는 2형 당뇨병, 대사 장애 진단을 받았거나 비만(예를 들어 체질량지수가 30.0 이상)이다. 다른 구현예에서, 본 발명의 방법에 따라 지방간 질환에 대한 치료 또는 예방이 필요하거나 지방간 질환이 발병할 위험이 있는 환자는 비-HDL 콜레스테롤 또는 트리글리세리드 수준이 상승된 환자이다. 특정 환자 및 환자가 가질 수 있는 다른 위험 인자에 따라 상승된 비-HDL 콜레스테롤 수준은 약 130 mg/dL 이상, 약 160 mg/dL 이상, 약 190 mg/dL 이상, 또는 약 220 mg/dL 이상일 수 있다. 상승된 트리글리세라이드 수준은 약 150 mg/dL 이상, 약 175 mg/dL 이상, 약 200 mg/dL 이상, 또는 약 250 mg/dL 이상일 수 있다.
특정 구현예에서, mARC1 발현의 감소를 필요로 하는 환자는 간 섬유증 또는 간경변으로 진단되거나 이의 발병 위험이 있는 환자이다. 따라서, 본 발명은 환자에게 본 발명의 임의의 RNAi 작제물을 투여하는 단계를 포함하는, 간 섬유증의 치료, 예방, 또는 감소를 필요로 하는 환자에서 이를 치료하거나, 예방하거나, 감소시키는 방법을 포함한다. 일부 구현예에서, 본 발명은 간 섬유증의 치료, 예방, 또는 감소를 필요로 하는 환자에서 이를 위한 의약의 제조에 있어서 본원에 기재된 임의의 RNAi 작제물의 용도를 포함한다. 다른 구현예에서, 본 발명은 간 섬유증의 치료, 예방, 또는 감소를 필요로 하는 환자에서 이를 위한 방법에 사용하기 위한 mARC1 표적 RNAi 작제물을 제공한다. 일부 구현예에서, 간 섬유증 또는 간경변이 발병할 위험이 있는 환자는 NAFLD로 진단된다. 다른 구현예에서, 간 섬유증 또는 간경변이 발병할 위험이 있는 환자는 NASH로 진단된다. 또 다른 구현예에서, 간 섬유증 또는 간경변이 발병할 위험이 있는 환자는 알코올성 지방간염으로 진단된다. 또 다른 구현예에서, 간 섬유증 또는 간경변이 발병할 위험이 있는 환자는 간염으로 진단된다. 특정 구현예에서, 본 발명의 RNAi 작제물의 투여는 환자에서 간경변의 진행을 예방하거나 지연시킨다.
수행된 실험 및 달성된 결과를 포함하는 하기 실시예는 단지 예시적 목적을 위해 제공되며 첨부되는 청구범위의 범위를 제한하는 것으로 간주되어서는 안 된다.
실시예
실시예 1. Ob/Ob 동물에서 mARC1 발현의 억제로 지질 수준 조절
유전 연구에서 MARC1 유전자의 A165T 미스센스 돌연변이와 감소된 혈청 저밀도 지단백(LDL) 콜레스테롤 및 총 콜레스테롤 수준 사이의 연관성이 보고되었다(문헌[Spracklen et al., Hum Mol Genet., Vol. 26(9):1770-178, 2017; Emdin et al., bioRxiv 594523; //doi.org/10.1101/594523, 2019; 및 Emdin et al., PLoS Genet, Vol. 16(4): e1008629, 2020)]). 해당 돌연변이뿐만 아니라 MARC1 유전자의 다른 기능상실 변이체 또한 최근 간 지방 수준 감소, 간 효소 수준 감소, 간경변 위험 감소와의 연관성이 보고되었다(문헌[Emdin et al., 2019 및 Emdin et al, 2020]). mARC1 발현 억제가 MARC1 A165T 변이 대립유전자의 인간 보인자에서 관찰된 바와 같이 혈청 콜레스테롤 수준을 감소시킬 수 있는지 여부를 평가하기 위해, 노화된 비만 마우스(ob/ob)에 마우스 Marc1 유전자를 표적으로 하는 siRNA 분자 또는 대조군 siRNA 분자를 투여하였다. Ob/ob 마우스는 비만이고 지질 수준이 상승되어 있으므로, 이러한 마우스는 종종 제2형 당뇨병 및 기타 대사 장애의 모델로 사용된다.
18~20주령의 수컷 ob/ob 동물(The Jackson Laboratory)에게 표준 차우(2020× Teklad global 콩단백질 불포함 압출 설치류 식이; Harlan)를 공급하였다. 마우스는 피하 주사를 통해 완충제(포스페이트-완충 식염수) 단독(n = 8), mARC1 표적 siRNA(이중체 번호 D-1000; n = 8), 또는 대조군 siRNA(이중체 번호 D-1002; n = 8)을 6주 동안 2주에 한 번 0.2 ml 완충제 중 체중 1 kg당 3 mg을 공급받았다. 하기 실시예 2에 기재된 바와 같이 siRNA 분자를 합성하고 3가 GalNAc 모이어티(화학식 VII에 도시된 구조)에 접합시켰다. 각 siRNA 분자의 구조는 하기 표 1 및 2에 제공되어 있다. 추가 분석을 위해 동물을 금식시키고 6주차에 수확하였다. 수확한 동물의 간의 총 RNA를 qPCR 분석을 위해 처리하고 혈청 파라미터를 임상 분석기(AU400 Chemistry Analyzer, Olympus)로 측정하였다. mRNA 수준을 먼저 각각의 간 샘플에서 18S 리보솜 RNA 수준으로 정규화한 후, 완충제 단독 군의 발현 수준과 비교하였다. 데이터는 완충제 단독 군에서의 발현 대비 상대적 배수로 제시하였다. 총 콜레스테롤 및 총 트리글리세라이드 측정을 위해 간 조직을 균질화하고 이소프로판올로 추출하였다(ThermoFisher, Infinity 콜레스테롤 및 Infinity 트리글리세라이드 시약). 모든 동물 수용 조건 및 연구 프로토콜은 Amgen Institutional Animal Care and Use Committee(IACUC)의 승인을 받았다. 마우스는 특정 병원균이 없는 AAALAC, Intl 인증 시설의 환기식 마이크로아이솔레이터에 수용하였다. 절차 및 수용실은 양압을 가하고 12:12 명:암 사이클로 조절하였다. 모든 동물에게 자동 급수 시스템을 통해 역삼투 정제수를 임의로 공급하였다.
mARC1 표적 siRNA로 처리한 동물은 완충제만 주사한 동물에 비해 간에서 mARC1 발현이 약 80% 감소한 것으로 나타났다(도 2a). siRNA 분자에 의한 mARC1 발현의 감소는 mARC2 mRNA의 간 발현에 영향을 미치지 않았기 때문에 특이적이었다(도 2b). mARC1 표적 siRNA로 처리하면 혈청 고밀도 지단백질(HDL), LDL, 및 총 콜레스테롤 수준은 물론 알라닌 아미노트랜스퍼라제(ALT) 및 C 반응성 단백질(CRP) 혈청 수준도 감소하였다(도 3a 내지 3h). 간의 트리글리세리드 수준은 또한 mARC1 표적 siRNA를 투여받은 ob/ob 동물에서도 감소하였다(도 4a 및 4b). mARC1 표적 siRNA를 투여받은 동물에서 섬유증 유전자의 간 발현은 해당 동물 모델에서 완충제 주입된 동물과 비교하여 유의하게 변경되지 않았다(데이터 미도시).
이 일련의 실험 결과는 mARC1 표적 siRNA 분자로 간에서 mARC1 발현을 특이적으로 억제하면 혈청 콜레스테롤, LDL 콜레스테롤, ALT 수준 및 간 트리글리세라이드를 감소시켜, 간세포의 지질 조절에 있어서 mARC1의 인과적 효과를 입증함을 보여준다. mARC1 표적 siRNA로 처리된 ob/ob 동물에서 관찰된 혈청 콜레스테롤, LDL 콜레스테롤, 및 ALT 수준의 감소는 MARC1 A165T 변이 대립유전자의 인간 보인자에서 관찰된 이러한 분석물의 수준 감소와 일치한다. 따라서, 본원에 기재된 것과 같은, siRNA 분자에 의한 mARC1 발현의 억제는 고콜레스테롤혈증 또는 고지혈증 장애가 있는 환자에서 콜레스테롤 및 트리글리세라이드 수준을 감소시키는 데 유용할 수 있고, 비알코올성 지방간 질환, 비알코올성 지방간염, 알코올성 지방간 질환, 알코올성 지방간염, 간 섬유증, 및 간경변과 같은 다른 간 장애에 대한 치료가 될 수 있다.
실시예 2. mARC1 siRNA 분자의 설계 및 합성
인간 MARC1 유전자를 표적화하는 치료용 siRNA 분자의 설계를 위한 후보 서열은 인간 MARC1 전사체의 생물정보학 분석을 사용하여 확인되었으며, 이의 서열은 본원에서 서열번호 1(Ensembl 전사체 번호 ENST00000366910.9; 도 1 참조)로 제공된다. 자체 siRNA 설계 알고리즘을 사용하여 서열을 분석하고 특정 기준이 충족되면 선택하였다. 생물정보학 분석은 두 단계로 수행하였다. 첫 번째 단계에서는 시노몰구스 원숭이(마카크 원숭이(Macaca fascicularis); NCBI 참조 서열번호 XR_001490722.1, XR_001490722.1, XR_001490723.1, XR_001490726.1, XR_273285.2, XM_005540901.2, XR_273286.2, XM_005540898.2, 및 XM_005540899.2)로부터의 MARC1 전사체와의 교차 반응성, 다른 인간, 시노몰구스 원숭이, 및 설치류 유전자 서열에 대한 서열 동일성, 및 알려진 인간 단일 뉴클레오티드 다형성과의 중첩을 포함하는 다양한 특징에 대해 서열을 평가하였다. 두 번째 단계에서는 선택 기준을 조정하여 인간 MARC1 전사체에만 특이성이 있는 서열을 포함하고, 인간 마이크로RNA(miRNA) 서열과 매칭되는 시드 영역에 대한 서열을 평가하여 비-표적 효과를 예측하였다. 생물정보학 분석 결과에 근거하여, 초기 합성 및 시험관내 시험을 위해 665개의 서열을 선택하였다.
고상 포스포라미다이트 화학을 이용하여 RNAi 작제물을 합성하였다. MerMade12 또는 MerMade192X(Bioautomation) 장비에서 합성을 수행하였다. 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 반전된 무염기 뉴클레오티드, 및 포스포로티오에이트 뉴클레오티드간 연결을 포함하는 다양한 화학적 변형을 분자에 혼입시켰다. RNAi 작제물은 일반적으로 안티센스 가닥 및/또는 센스 가닥의 3' 말단에서 오버행이 없거나(이중 블런트머(double bluntmer)) 또는 2개 뉴클레오티드의 1개 또는 2개의 오버행으로 어닐링될 때 19~21개 염기쌍의 이중체가 되도록 구성하였다. 생체내 연구를 위해, RNAi 작제물의 센스 가닥을 하기에 추가로 기재된 바와 같이 3가 N-아세틸-갈락토사민(GalNAc) 모이어티에 접합시켰다.
재료
아세토니트릴(DNA 합성 등급, AXO152-2505, EMD)
캡핑 시약 A(80:10:10 (v/v/v) 테트라하이드로퓨란/루티딘/무수 아세트산, BIO221/4000, EMD)
캡핑 시약 B(16%의 1-메틸이미다졸/테트라하이드로퓨란, BIO345/4000, EMD)
활성화제 용액(아세토니트릴 중 0.25 M의 5-(에틸티오)-1H-테트라졸(ETT), BIO152/0960, EMD)
탈트리틸화 시약(디클로로메탄 중 3%의 디클로로아세트산, BIO830/4000, EMD)
산화 시약(70:20:10(v/v/v)의 테트라하이드로퓨란/피리딘/물 중 0.02 M의 요오드, BIO420/4000, EMD)
디에틸아민 용액(아세토니트릴 중 20%의 DEA, NC0017-0505, EMD)
티올화 시약(피리딘 중 0.05 M의 5-N-[(디메틸아미노)메틸렌]아미노-3H-1,2,4-디티아졸-3-티온(BIOSULII/160K))
아데노신, 구아노신, 및 시토신의 5'-아미노헥실 링커 포스포르아미다이트 및 2'-메톡시 및 2'-플루오로 포스포르아미다이트(Thermo Fisher Scientific), 분자 트랩 팩(30 mL당 0.5 g, Bioautomation)의 아세토니트릴 중 0.10 M
2'-메톡시-우리딘 포스포르아미다이트(Thermo Fisher Scientific), 분자 트랩 팩(30 mL당 0.5 g, Bioautomation)의 90:10 (v/v) 아세토니트릴/DMF 중 0.10 M
2'-데옥시-역 무염기 포스포르아미다이트(ChemGenes), 분자 트랩 팩(30 mL당 0.5 g, Bioautomation)의 아세토니트릴 중 0.10 M
CPG Support(Hi-Load Universal Support, 500A(BH5-3500-G1), 79.6 μmol/g, 0.126 g(10 μmol)) 또는 1 μmol Universal Synthesis Column, 500A, Pipette Style Body(MM5-3500-1, Bioautomation)
수산화암모늄(농축형, J. T. Baker)
합성
시약 용액, 포스포라미다이트 용액, 및 용매를 MerMade12 또는 MerMade192X 장비에 부착하였다. 고체 지지체를 각 컬럼(10 μmol용 상부 및 하부의 프릿이 있는 4 mL의 SPE 튜브)에 첨가하고, 컬럼을 장비에 고정시켰다. 컬럼을 아세토니트릴로 2회 세척하였다. 포스포라미다이트 및 시약 용액 라인을 퍼징시켰다. 포세이돈 소프트웨어를 이용하여 합성을 개시하였다. 탈보호/커플링/산화/캡핑 합성 사이클을 반복하여 합성을 달성하였다. 구체적으로, 고체 지지체에 탈트리틸화 시약을 첨가하여 5'-디메톡시트리틸(DMT) 보호기를 제거하였다. 고체 지지체를 아세토니트릴로 세척하였다. 지지체에 포스포라미다이트 및 활성화제 용액을 첨가한 후, 인큐베이션시켜 유입되는 뉴클레오티드를 유리 5'-하이드록실기에 커플링시켰다. 지지체를 아세토니트릴로 세척하였다. 지지체에 산화 또는 티올화 시약을 첨가하여 포스파이트 트리에스테르를 포스페이트 트리에스테르 또는 포스포로티오에이트로 전환시켰다. 지지체에 캡핑 시약 A 및 B를 첨가하여 임의의 반응하지 않은 올리고뉴클레오티드 쇄를 차단하였다. 지지체를 아세토니트릴로 세척하였다. 최종 반응 사이클 후, 수지를 디에틸아민 용액으로 세척하여 2-시아노에틸 보호기를 제거하였다. 지지체를 아세토니트릴로 세척하고, 진공 건조시켰다.
GalNAc 접합
3가 GalNAc 모이어티(아래 화학식 VII에 도시된 구조)에 접합시키기 위한 센스 가닥을 5'-아미노헥실 링커로 제조하였다. 자동화된 합성 후, 장비로부터 컬럼을 제거하여 후드 안의 진공 매니폴드로 옮겼다. 진공 여과와 함께 디클로로메탄(DCM) 중 1%의 트리플루오로아세트산(TFA)의 2 mL의 분취량으로 연속 처리하여 고체 지지체로부터 5'-모노메톡시트리틸(MMT) 보호기를 제거하였다. 용출액에서 주황색/황색을 더 이상 관찰할 수 없을 때, 수지를 디클로로메탄으로 세척하였다. 수지를 N,N-디메틸포름아미드(DMF) 중 10%의 디이소프로필에틸아민 5 mL로 세척하였다. 별도의 바이알에서 DMF(0.5 mL) 중 GalNAc3-Lys2-Ahx(67 mg, 40 μmol)의 용액(이의 구조 및 합성은 아래에 기술됨)을 1,1,3,3-테트라메틸우로늄 테트라플루오로보레이트(TATU, 12.83 mg, 40 μmol) 및 디이소프로필에틸아민(DIEA)(13.9 μL, 80 μmol)으로 제조하였다. 활성화된 커플링 용액을 수지에 첨가하고, 컬럼을 캡핑하고 실온에서 밤새 인큐베이션하였다. 수지를 DMF, DCM으로 세척하고, 진공 건조시켰다.
절단
합성 컬럼을 합성기 또는 진공 매니폴더로부터 제거하고, 절단 장치로 이동시켰다. 고체 지지체에 4 x 1 mL(10 μmol의 경우) 또는 4 x 250 μL(1 μmol의 경우)의 농축 수산화암모늄을 첨가하였다. 용출액을 중력 또는 광진공 여과를 통해 각각 24-웰 또는 96-웰 딥웰 플레이트에 수집하였다. 플레이트를 밀봉하고 절단 척(Bioautomation)에 볼트로 고정하고 혼합물을 55°C에서 4시간 동안 가열하였다. 플레이트를 냉동고로 옮기고 20분 동안 냉각시킨 후, 후드에서 절단 척을 열었다.
분석 및 정제
절단 용액의 일부분을 분석하고, 음이온 교환 크로마토그래피로 정제하였다. 모은 분획을 크기 배제 크로마토그래피로 탈염시키고, 이온쌍 역상 고성능 액체 크로마토그래피-질량 분광분석법(HPLC-MS)으로 분석하였다. 모은 분획을 동결건조시켜 흰색의 무정형 분말을 수득하였다.
분석적 음이온 교환 크로마토그래피(AEX):
컬럼: Thermo DNAPac PA200RS(4.6 x 50 mm, 4 μm)
기기: Agilent 1100 HPLC
완충제 A: 20 mM의 인산나트륨, 10%의 아세토니트릴, pH 8.5
완충제 B: 20 mM의 인산나트륨, 10%의 아세토니트릴, pH 8.5, 1 M의 브롬화나트륨
유속: 40℃에서 1 mL/분
구배: 6.2분 내에 20~65% B
분취용 음이온 교환 크로마토그래피(AEX):
컬럼: Tosoh TSK Gel SuperQ-5PW, 21 x 150 mm, 13 μm
기기: Agilent 1200 HPLC
완충제 A: 20 mM의 인산나트륨, 10%의 아세토니트릴, pH 8.5
완충제 B: 20 mM의 인산나트륨, 10%의 아세토니트릴, pH 8.5, 1 M의 브롬화나트륨
유속: 8 mL/분
주입량: 5 mL
구배: 센스 가닥의 경우 40분 동안 35~55%의 B 및 안티센스 가닥의 경우 40분 동안 50~100%의 B
분취용 크기 배제 크로마토그래피(SEC):
컬럼: 3 x GE Hi-Prep 26/10 직렬
기기: GE AKTA Pure
완충제: 물 중 20%의 에탄올
유속: 10 mL/분
주입량: 샘플 로딩 펌프를 이용, 45 mL
이온쌍-역상(IP-RP) HPLC:
컬럼: Water Xbridge BEH OST C18, 2.5 μm, 2.1 x 50 mm
기기: Agilent 1100 HPLC
완충제 A: 물 중 15.7 mM의 DIEA, 50 mM의 헥사플루오로이소프로판올(HFIP)
완충제 B: 50:50의 물/아세토니트릴 중 15.7 mM의 DIEA, 50 mM의 HFIP
유속: 0.5 mL/분
구배: 6분에 걸쳐 10~30% B
어닐링
소량의 센스 가닥과 안티센스 가닥을 개별 바이알에 칭량하였다. 바이알에 포스페이트 완충 식염수(PBS, Gibco)를 건조 중량을 기준으로 약 2 mM의 농도로 첨가하였다. 실제 샘플 농도를 NanoDrop One(ssDNA, 흡광 계수 = 33 μg/OD260)에서 측정하였다. 그 후, 두 가닥을 등몰 비율로 혼합하고, 샘플을 90℃의 인큐베이터에서 5분 동안 가열하고, 실온까지 서서히 냉각되게 하였다. 샘플을 AEX로 분석하였다. 하기 실시예 3 및 4에 보다 상세히 기술된 바와 같이, 이중체를 등록하고 생체내 시험을 위해 제출하였다.
GalNAc3-Lys2-Ahx의 제조
[화학식 VII]
Figure pct00011
상기 식에서 X = O 또는 S이다. 구불구불한 선은 RNAi 작제물의 센스 가닥의 5' 말단 뉴클레오티드에 대한 부착점을 나타낸다. GalNAc 모이어티는, 반전된 무염기(invAb) 데옥시뉴클레오티드가 5' 말단 뉴클레오티드이고 5'-5' 뉴클레오티드간 연결을 통해 인접 뉴클레오티드에 연결된 경우(이 경우 GalNAc 모이어티는 반전된 무염기 데옥시뉴클레오티드의 3' 탄소에 부착됨)를 제외하고, 센스 가닥의 5' 말단 뉴클레오티드의 5' 탄소에 부착되었다.
50 mL의 팔콘 튜브에 DCM(30 mL) 중 Fmoc-Ahx-OH(1.13 g, 3.19 mmol)를 첨가하고, DIEA(2.23 mL, 12.78 mmol)를 첨가하였다. 용액을 50 mL의 원심분리 튜브의 2-Cl 염화트리틸 수지(3.03 g, 4.79 mmol)에 첨가하고, 2시간 동안 진탕기에 로딩하였다. 용매를 따라내고, 수지를 17:2:1의 DCM/MeOH/DIEA(30 ml x 2), DCM(30 ml x 4)으로 세척하고 건조시켰다. 로딩은 290 nm에서 UV 분광광도계 검출로 0.76 mmol/g으로 확인되었다.
로딩된 2-Cl 트리틸 수지 3 g을 DMF(20 mL) 중 20%의 4-메틸피페리딘에 현탁시키고, 30분 후 용매를 따라냈다. 이 과정을 한 번 더 반복하고, 수지를 DMF(30 mL x 3) 및 DCM(30 mL x 3)으로 세척하였다.
DMF(20 mL) 중의 Fmoc-Lys(ivDde)-OH(3.45 g, 6 mmol)의 용액에 TATU(1.94 g, 6 mmol)에 이어 DIEA(1.83 mL, 10.5 mmol)를 첨가하였다. 이어서, 용액을 상기 탈보호된 수지에 첨가하고, 현탁액을 밤새 진탕기에 두었다. 용매를 따라내고, 수지를 DMF(30 mL x3) 및 DCM(30 mL x3)으로 세척하였다.
수지를 DMF(15 mL) 중 20%의 4-메틸피페리딘으로 처리하고, 10분 후 용매를 따라냈다. 이 과정을 한 번 더 반복하고 수지를 DMF(15 mL x 4) 및 DCM(15 mL x 4)으로 세척하였다.
DMF(20 mL) 중 Fmoc-Lys(Fmoc)-OH(3.54 g, 6 mmol)의 용액에 TATU(1.94 g, 6 mmol)에 이어 DIEA(1.83 mL, 10.5 mmol)를 첨가하였다. 이어서, 용액을 상기 탈보호된 수지에 첨가하고, 현탁액을 밤새 진탕기에 두었다. 용매를 따라내고, 수지를 DMF(30 mL x3) 및 DCM(30 mL x3)으로 세척하였다.
수지를 DMF(20 mL) 중 5%의 히드라진으로 처리하고, 5분 후 용매를 따라냈다. 이 과정을 4회 더 반복하고, 수지를 DMF(30 mL x 4) 및 DCM(30 mL x 4)으로 세척하였다.
DMF(40 mL) 중 5-(((2R,3R,4R,5R,6R)-3-아세트아미도-4,5-디아세톡시-6-(아세톡시메틸)테트라하이드로-2H-피란-2-일)옥시)펜탄산(4.47 g, 10 mmol)의 용액에 TATU(3.22 g, 10 mmol)를 첨가하고, 용액을 5분 동안 교반하였다. DIEA(2.96 mL, 17 mmol)를 용액에 첨가하고, 이어서 혼합물을 상기 수지에 첨가하였다. 현탁액을 밤새 실온으로 유지하고, 용매를 따라냈다. 수지를 DMF(3 x 30 mL) 및 DCM(3 x 30 mL)으로 세척하였다.
수지를 DCM(30 mL, 3%의 트리이소프로필실란 함유) 중 1%의 TFA로 처리하고, 5분 후 용매를 따라냈다. 이 과정을 3회 더 반복하고, 합한 여과액을 진공 농축시켰다. 잔류물을 디에틸 에테르(50 mL)로 저작(trituration)하고, 현탁액을 여과하고 건조시켜 미정제 생성물을 수득하였다. 미정제 생성물을 역상 크로마토그래피로 정제하고, 물 중 0~20%의 MeCN으로 용출시켰다. 분획을 합하고 동결건조시켜 생성물을 백색 고체로 수득하였다.
하기의 표 1은 생물정보학 분석에서 우선순위가 정해진 분자에 대한 변형되지 않은 센스 및 안티센스 서열을 나열한 것이다. 인간 MARC1 전사체(서열번호 1) 내의 각 서열 패밀리에서 siRNA 분자에 의해 표적화된 뉴클레오티드의 범위 또한 표 1에 제시되어 있다. 이중체 번호 D-1000 내지 D-1003은 Marc1 마우스 전사체를 표적으로 하고 인간 MARC1 전사체와 교차 반응하지 않도록 설계되었다. 표 2는 화학적 변형이 있는 센스 및 안티센스 가닥의 서열을 제공한다. 각각 실시예 3 및 4에 기술된 바와 같은 시험관내 세포 기반 분석 및 생체내 마우스 연구에서의 활성에 근거하여, 구조-활성 관계(SAR) 연구를 위해 인간 MARC1 전사체의 특정 영역을 표적화하는 서열을 선택하였다. 뉴클레오티드 서열은 하기 표기법에 따라 열거된다: a, u, g, 및 c = 상응하는 2'-O-메틸 리보뉴클레오티드; Af, Uf, Gf, 및 Cf = 상응하는 2'-데옥시-2'-플루오로("2'-플루오로") 리보뉴클레오티드; 및 invAb = 반전된 무염기 뉴클레오티드(즉, 가닥의 3' 말단에 있을 경우 3' 위치의 치환기(3'-3' 연결)를 통해 인접 뉴클레오티드에 연결되거나, 가닥의 5' 말단에 있을 경우 5' 위치의 치환기(5'-5' 뉴클레오티드간 연결)를 통해 인접 뉴클레오티드에 연결된 무염기 뉴클레오티드). 서열에서 "s"의 삽입은 2개의 인접 뉴클레오티드가 포스포로티오디에스테르기에 의해 연결(예를 들어, 포스포로티오에이트 뉴클레오티드간 연결)됨을 나타낸다. 달리 지시되지 않는 한, 다른 모든 뉴클레오티드는 3'-5' 포스포디에스테르기에 의해 연결된다. [GalNAc3]는 화학식 VII에 나타낸 GalNAc 모이어티를 나타내며, 이는 "s"가 [GalNAc3] 표기법 뒤에 오는 경우 포스포디에스테르 결합 또는 포스포로티오에이트 결합을 통해 센스 가닥의 5' 말단의 5' 말단 뉴클레오티드에 공유 결합된 것이다. invAb 뉴클레오티드가 센스 가닥의 5' 말단의 5' 말단 뉴클레오티드일 때, 5'-5' 연결을 통해 인접 뉴클레오티드에 연결되었고 GalNAc 모이어티는 invAb 뉴클레오티드의 3' 탄소에 공유 결합되었다. 그렇지 않은 경우, GalNAc 모이어티는 센스 가닥의 5' 말단 뉴클레오티드의 5' 탄소에 공유 결합되었다.
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실시예 3. 세포 기반 분석에서 mARC1 siRNA 분자의 시험관내 평가
실시예 2에 기재된 생물정보학 분석으로부터 우선순위가 정해진 상이한 서열을 갖는 mARC1 siRNA 분자를 RNA FISH(형광동소보합법) 분석을 사용하여 인간 mARC1 mRNA를 감소시키는 효능에 대해 스크리닝하였다. Hep3B 세포(ATCC에서 구입)를 10% 태아 소 혈청(FBS, Sigma) 및 1% 페니실린-스트렙토마이신(P-S, Corning)이 보충된 Eagle's Minimum Essential Medium(EMEM)(ATCC 30-2003)에서 배양하였다. siRNA를 Lipofectamine RNAiMAX 형질감염 시약(Thermo Fisher Scientific)을 사용하여 역 형질감염으로 세포에 형질감염시켰다. mARC1 siRNA 분자는 10포인트 용량 반응 포맷에서 3배 희석하여 500 nM 내지 25 pM(실행 1), 25 nM 내지 1 pM(실행 2), 또는 100 nM 내지 5 pM(실행 3) 범위의 최종 농도로 시험하였다. 시험 siRNA 분자 또는 포스페이트 완충 식염수(PBS) 비히클 1 μL 및 보충제 없는 4 μL의 염기 EMEM을 Bravo 자동 액체 처리 플랫폼(Agilent)으로 PDL 코팅된 CellCarrier-384 Ultra 분석 플레이트(PerkinElmer)에 첨가하였다. 보충제 없는 염기 EMEM(5 μL의 MEM 중 0.035 μL의 RNAiMAX)에 사전-희석된, 5 μL의 리포펙타민 RNAiMAX(Thermo Fisher Scientific)을 Multidrop Combi 시약 분주기(Thermo Fisher Scientific)로 분석 플레이트에 분주하였다. 실온(RT)에서 siRNA/RNAiMAX 혼합물을 20분 동안 인큐베이션한 후, 10% FBS 및 1% P-S가 보충된 EMEM 중의 30 μL의 Hep3B 세포(웰당 2000개 세포)를 Multidrop Combi 시약 분주기를 사용하여 형질감염 복합체에 첨가하였다. 분석 플레이트를 인큐베이터에 위치시키기 전에 실온에서 20분 동안 인큐베이션하였다. 세포를 37℃ 및 5% CO2에서 72시간 동안 인큐베이션하였다. RNA FISH 분석은 자체 조립된 자동 FISH 분석 플랫폼에서 제조업체의 분석 시약 및 프로토콜(Thermo Fisher Scientific의 QuantiGene® ViewRNA HC Screening Assay)을 사용하여 siRNA 형질감염 72시간 후 수행하였다. 간략하게, 세포를 실온에서 15분 동안 4% 포름알데히드(Thermo Fisher Scientific)에 고정시키고, 실온에서 3분 동안 시약으로 투과시킨 후, 실온에서 10분 동안 프로테아제 용액으로 처리하였다. 표적 특이적 프로브(Thermo Fisher Scientific) 또는 비히클(음성 대조군으로서 표적 프로브가 없는 표적 프로브 희석액)은 3시간 동안 인큐베이션한 반면 전치증폭기, 증폭기, 및 라벨 프로브는 각각 1시간 동안 인큐베이션하였다. 모든 하이브리드화 단계는 Cytomat 2 C-LIN 자동 인큐베이터(Thermo Fisher Scientific)에서 40℃에서 수행되었다. 하이브리드화 반응 후, 세포를 Hoechst 및 CellMask Blue(Thermo Fisher Scientific)로 30분 동안 염색한 후, Opera Phenix 고효율 스크리닝 시스템(PerkinElmer)에서 영상화하였다. 콜럼버스 이미지 데이터 저장 및 분석 시스템(PerkinElmer)을 사용하여 이미지를 분석하여 세포당 평균 스팟 카운트를 얻었다. 세포당 평균 스팟 카운트는 높은(표적 프로브가 있는 PBS) 및 낮은(표적 프로브가 없는 PBS) 대조군 웰을 사용하여 정규화하였다. 총 siRNA 농도에 대한 정규화된 값을 플롯팅하고 데이터를 Genedata Screener 데이터 분석 소프트웨어(Genedata)를 사용하여 4-파라미터 시그모이드 모델에 맞추어 IC50 및 최대 활성값을 얻었다. 데이터가 모델에 맞지 않으면 IC50 값이 계산되지 않고 최대 활성값만 보고되었다.
mARC1 siRNA 분자는 초기에 500 nM 내지 25 pM 범위의 10개의 상이한 농도로 1차 실행에서 스크리닝하였다. 1차 실행에서 상당한 활성을 나타내는 siRNA 분자를 더 좁은 농도 범위(실행 2: 25 nM 내지 1 pM; 실행 3: 100 nM 내지 5 pM)에 걸쳐 10개의 상이한 농도로 2차 및 3차 실행에서 스크리닝하였다. 세 가지 실행 모두에 대한 분석 결과는 하기의 표 3에 제시되어 있다.
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RNA FISH 분석에서 평가된 초기 257개의 mARC1 siRNA 분자 중 74개 분자는 평균 80% 이상의 인간 mARC1 mRNA 녹다운을 나타냈고 분석 실행 2 및 3에서 IC50 값이 적어도 한 자릿수 나노몰 범위에 있었다. 특히, 32개의 분자(이중체 번호 D-1092; D-1093; D-1139; D-1061; D-1138; D-1095; D-1191; D-1180; D-1090; D-1062; D-1177; D-1083; D-1245; D-1067; D-1143; D-1170; D-1044; D-1096; D-1113; D-1086; D-1256; D-1189; D-1091; D-1174; D-1185; D-1066; D-1171; D-1140; D-1130; D-1068; D-1243; D-1074)는 분석 실행 2 및 3 중 하나 또는 둘 모두에서 인간 mARC1 mRNA를 적어도 85% 감소시켰다.특히, 32개의 분자는 분석 실행 2 및 3 중 하나 또는 둘 모두에서 인간 mARC1 mRNA를 적어도 85% 만큼 감소시켰다.
제2의 일련의 실험에서, RNA FISH 분석에서 추가 mARC1 siRNA 분자를 100 nM 내지 5 pM 범위의 10개의 상이한 농도로 평가하고 IC50 및 최대 활성값을 전술한 바와 같이 계산하였다. 이러한 제2의 일련의 실험의 분석 결과는 하기의 표 4에 제시되어 있다. 분자의 하위집합에 대해 분석을 반복하였다. 이러한 분자의 경우 두 실행에 대한 IC50 및 최대 활성값이 제시되어 있다.
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인간 mARC1 전사체의 다른 영역을 표적화하는 추가 406개의 mARC1 siRNA 분자 중 128개의 분자가 Hep3B 세포에서 85% 이상의 인간 mARC1 mRNA 감소를 보였다. 46개의 분자(이중체 번호 D-1061; D-1093; D-1220; D-1276; D-1284; D-1298; D-1310; D-1311; D-1338; D-1363; D-1367; D-1375; D-1381; D-1382; D-1383; D-1386; D-1387; D-1388; D-1389; D-1390; D-1396; D-1400; D-1401; D-1402; D-1405; D-1407; D-1416; D-1420; D-1421; D-1441; D-1451; D-1487; D-1489; D-1491; D-1503; D-1504; D-1515; D-1549; D-1576; D-1581; D-1595; D-1596; D-1606; D-1626; D-1633; 및 D-1662)는 인간 mARC1 mRNA를 적어도 90% 만큼 감소시켰으며 대부분의 분자는 IC50 값이 1 nM 미만이었다.
실시예 4. AAV 인간 mARC1 마우스 모델에서 siRNA 분자의 생체내 효능
생체내 mARC1 siRNA 분자의 효능을 평가하기 위해, 각 siRNA 분자의 센스 가닥을 실시예 2에 기술된 방법으로 화학식 VII에 나타낸 3가 GalNAc 모이어티에 접합시키고 mARC1 siRNA 분자를 인간 MARC1 유전자를 발현하는 마우스에 투여하였다. 10~12주령의 C57BL/6 마우스(The Jackson Laboratory)에게 표준 차우(Harlan, 2020× Teklad global 콩단백질 불포함 압출 설치류 식이)를 공급하였다. 마우스에 인간 MARC1 유전자(AAV-hmARC1)를 암호화하는 아데노 관련 바이러스(AAV)를 동물당 1×1011 게놈 카피(GC)의 용량으로 복강내(i.p.) 주사하였다. AAV-hmARC1 주사 1주 후, 마우스에 완충제 또는 mARC1 siRNA 분자를 완충제 중 0.5 mg/kg, 1 mg/kg, 또는 3 mg/kg(체중)의 용량으로 단일 피하(s.c.)로 주사하였다(각 군당 n=3). 추가 분석을 위해 동물을 금식시키고 siRNA 투여 4주 후에 수확하였다. 수확한 동물의 간의 총 RNA를 qPCR 분석을 위해 처리하고 혈청 파라미터를 임상 분석기(AU400 Chemistry Analyzer, Olympus)로 측정하였다. 각각의 동물에 대한 간에서의 인간 mARC1 mRNA의 백분율 변화는 인간 mARC1 mRNA를 발현하고 완충제만 주사한 대조군 동물(즉, AAV-hmARC1 단독 동물)에서 인간 mARC1 mRNA 간 수준에 상대적으로 계산하였다.
해당 모델에서 생체내 효능에 대해 실시예 3에 기술된 시험관내 활성 분석으로부터의 최고 수행 mARC1 siRNA 분자를 평가하였다. 화학적 변형 패턴을 변경하여 생체내 효능과 내구성을 추가로 개선하기 위해 상당한 생체내 녹다운 활성을 나타낸 mARC1 siRNA 분자를 SAR 연구에서 추가로 평가하였다. 상이한 mARC1 siRNA 분자를 갖는 AAV-hmARC1 마우스 모델에서의 18개의 개별 연구 결과가 하기의 표 5 내지 22에 제시되어 있다. 데이터는 각 처리 군(n = 3마리 동물/군)에 대해 연구 5주차(siRNA 주입 4주 후)에 대조군으로부터의 평균 백분율 변화로 표시된다. mARC1 siRNA 분자가 다른 mARC1 siRNA 분자와 동일한 트리거 패밀리 명칭을 갖는 경우 두 분자는 동일한 핵심 서열(즉, mARC1 전사체의 동일한 영역을 표적화함)을 갖지만 화학적 변형 패턴이 상이하다.
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초기 생체 내 연구(이중체 번호 D-2042 및 D-2081)에서 상당한 사일런싱 활성을 나타낸 두 개의 mARC1 siRNA 분자를 후에 생체내 연구에서 벤치마크 화합물로 사용하였다. 70개의 mARC1 siRNA 분자는 1 mg/kg의 용량의 단일 s.c. 주사 후 4주차에 AAV-hmARC1 마우스에서 인간 mARC1 mRNA가 75% 이상 감소를 보였다. D-2081, D-2241, D-2255, 및 D-2258을 포함하여 시험한 mARC1 siRNA 분자 중 일부는 0.5 mg/kg의 용량으로 단 한번의 s.c. 주사 후 4주차에 인간 mARC1 mRNA가 85% 이상 감소하여 입증된 바와 같이 특히 강력하였다. 또한, 인간 mARC1 전사체의 특정 영역을 표적화하는 mARC1 siRNA 분자는 전사체의 다른 영역을 표적화하는 mARC1 siRNA 분자와 비교하여 생체내에서 인간 mARC1 mRNA의 더 큰 감소를 생성하는 것으로 관찰되었다. 예를 들어, 뉴클레오티드 1205 내지 1250, 뉴클레오티드 1345 내지 1375, 또는 뉴클레오티드 2039 내지 2078 사이의 인간 mARC1 전사체(서열번호 1)의 영역에 상보적인 서열을 갖는 안티센스 가닥을 갖는 mARC1 siRNA 분자는 1 mg/kg 용량의 단일 s.c. 주사 후 4주차에 상당한 녹다운 활성을 나타냈다(표 23). 표 23은 동일한 화학적 변형 패턴을 갖고 지정된 뉴클레오티드 범위에서 인간 전사물을 표적화하는 siRNA 분자에 대해 상기 기술된 연구로부터 인간 mARC1 mRNA 간 수준의 평균 백분율 변화를 요약한 것이다. 뉴클레오티드 1211 내지 1236 사이의 인간 전사체를 표적화하는 mARC1 siRNA 분자는, 이러한 siRNA 분자를 1 mg/kg 용량의 단일 s.c. 투여하여 투약 후 적어도 4주 동안 인간 mARC1 mRNA 수준이 80% 이상 감소됨에 따라 특히 효과를 보였다.
Figure pct00172
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실시예 5. 마우스 모델에서 NASH 치료에서의 mARC1 siRNA 효능
mARC1 발현 억제가 지방간 질환에 대한 치료적 효과가 있는지 확인하기 위해, 0.2% 콜레스테롤 식이(TD190883 식이)를 적용한 마우스에 마우스 Marc1 유전자를 표적으로 하는 siRNA 분자 또는 대조군 siRNA 분자를 투여하였다. TD190883 식이는 콜레스테롤 0.2%, 과당 20%, 자당 12%, 수소화 식물성 오일(HVO) 22%를 포함한다. 유사한 식이가 몇 주에 걸친 해당 식이를 적용한 마우스에서 NAFLD 및 NASH의 특징을 유도하는 것으로 나타났다(예를 들어 문헌[Zhong et al., Digestion, Vol. 101:522-535, 2020 및 Kroh et al., Gastroenterol Res Pract. Vol. 2020:7347068, 2020, doi:10.1155/2020/7347068] 참조).
6주령 수컷 c57BL/6 마우스(Charles River Laboratories)에게 표준 차우(Harlan, 2020× Teklad global 콩단백질 불포함 압출 설치류 식이) 또는 0.2% 콜레스테롤 식이(TD190883, Envigo)를 공급하였다. 0.2% 콜레스테롤 식이를 적용한 마우스에게 24주 동안 2주에 한 번, 완충제 단독(포스페이트 완충 식염수), mARC1 표적 siRNA(이중체 번호 D-1000), 또는 대조군 siRNA(이중체 번호 D-1002)를 0.2 ml 완충제 중 3 mg/kg(체중)으로 피하 주사하였다. 실시예 2에 기재된 바와 같이 siRNA 분자를 합성하고 3가 GalNAc 모이어티(화학식 VII에 도시된 구조)에 접합시켰다. 각 siRNA 분자의 구조는 표 1 및 2에 제공되어 있다. 추가 분석을 위해 동물을 금식시키고 24주차에 수확하였다. 수확한 동물의 간의 총 RNA를 qPCR 분석을 위해 처리하고 혈청 파라미터를 임상 분석기(AU400 Chemistry Analyzer, Olympus)로 측정하였다. mRNA 수준을 먼저 각각의 간 샘플에서 18S 리보솜 RNA 수준으로 정규화한 후, 차우 대조군의 발현 수준과 비교하였다. 데이터는 차우 대조군에서의 발현 대비 상대적 배수로 제시하였다. 총 콜레스테롤 및 총 트리글리세라이드 측정을 위해 간 조직을 균질화하고 이소프로판올로 추출하였다(ThermoFisher, Infinity 콜레스테롤 및 Infinity 트리글리세라이드). 모든 동물 수용 조건 및 연구 프로토콜은 Amgen Institutional Animal Care and Use Committee(IACUC)의 승인을 받았다. 마우스는 특정 병원균이 없는 AAALAC, Intl 인증 시설의 환기식 마이크로아이솔레이터에 수용하였다. 절차 및 수용실은 양압을 가하고 12:12 명:암 사이클로 조절하였다. 모든 동물에게 자동 급수 시스템을 통해 역삼투 정제수를 임의로 공급하였다.
mARC1 및 mARC2 둘 모두 간 발현이 0.2% 콜레스테롤 식이를 공급한 마우스에서 감소하였다. mARC2 발현이 아닌, mARC1 발현이 mARC1 표적 siRNA로 처리된 동물에서 추가로 감소하였다(도 5a 및 5b). 예상한 바와 같이, 0.2% 콜레스테롤 식이를 공급한 마우스는 연구 기간 동안 간 효소(AST 및 ALT), 콜레스테롤, LDL 콜레스테롤(LDL-C), 및 HDL-콜레스테롤(HDL-C)의 혈청 수준이 증가하였다(도 6a 내지 6e). mARC1 표적 siRNA를 사용한 처리는 혈청 콜레스테롤, LDL-C, 및 HDL-C의 식이 유발 증가를 감소시켰다(도 6c 내지 6e). mARC1 siRNA 처리는 또한 간 효소의 식이 유발 혈청 수준을 감소시키는 경향을 보였다(도 6a 및 6b). 0.2% 콜레스테롤 식이를 공급한 동물은 24주 후에 체중과 간 중량이 증가하였다(도 7a 및 7b). 24주차에 0.2% 콜레스테롤 식이를 공급한 동물의 간에서 트리글리세리드 및 콜레스테롤 수준도 증가하였다(도 7c 및 7d). mARC1 siRNA 처리는 체중, 간 중량, 간 트리글리세리드 수준 또는 간 콜레스테롤 수준의 식이 유발 증가를 유의하게 감소시키지 않았다(도 7a 내지 7d).
요컨대, 해당 연구의 결과는 mARC1 표적 siRNA 분자로 mARC1 간 발현을 억제하면 NASH 마우스 모델에서 혈청 콜레스테롤, LDL-C, HDL-C, 및 간 효소가 감소함을 보여주며, 이는 mARC1 siRNA 분자가 해당 질병 및 기타 지방간 장애를 치료하기 위한 새로운 치료적 접근이 될 수 있음을 시사한다.
실시예 6. mARC1 siRNA 분자의 효능에 대한 미스매치의 영향
염기쌍 미스매치가 mARC1 siRNA 분자의 효능에 미치는 영향을 평가하기 위해, 안티센스 가닥의 5' 말단으로부터 위치 6 또는 8번에 상이한 뉴클레오티드를 갖도록 가장 강력한 siRNA 분자의 하위 집합 유사체를 합성하여, 안티센스 가닥이 mARC1 mRNA 전사체의 표적 영역에 혼성화될 때 해당 위치에서 염기쌍 미스매치가 발생하도록 하였다. 그러나, 각각의 유사체에서, 센스 가닥의 서열은 안티센스 가닥의 서열에 완전히 상보적이 되도록 설계되어 siRNA 이중체에서 센스 가닥과 안티센스 가닥 사이에 미스매치가 발생하지 않았다. 각각의 미스매치 유사체(이중체 번호 D-2514 내지 D-2561) 및 모 siRNA 분자(이중체 번호 D-2052, D-2072, D-2076, D-2077, D-2079, D-2081, D-2105, D-2108, D-2111, D-2113, D-2115, D-2118, D-2142, D-2136, D-2189, D-2196, D-2238, D-2241, D-2254, D-2258, D-2301, D-2462, D-2465, 및 D-2510)에 대한 변형되지 않은 및 변형된 서열은 각각 표 1 및 2에 제공된다. 인간 mARC1 mRNA 수준을 감소시키는 데 있어서의 미스매치 유사체 및 모 siRNA 분자의 효능을 상기 실시예 3에 기술된 시험관내 RNA FISH 분석을 사용하여 Hep3B 세포에서 평가하였다. 100 nM 내지 5 pM 범위의 각각의 siRNA 분자의 10개의 상이한 농도를 시험하고, 실시예 3에 기술된 바와 같이 용량 반응 곡선으로부터 IC50 및 최대 활성값을 계산하였다. 해당 분석 결과는 하기의 표 24에 제공된다.
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대부분의 분자의 경우, 안티센스 가닥의 시드 영역 내에 위치한 위치 6 및 8번의 미스매치는, 안티센스 가닥이 표적 mARC1 mRNA 서열에 완전히 상보적인 모 분자와 비교하여, siRNA 분자의 최대 녹다운 활성 또는 효능에 유의미한 영향을 미치지 않았다. 이러한 결과는 안티센스 가닥의 시드 영역(즉, 5' 말단으로부터 뉴클레오티드 2 내지 8)이 온-타겟 효능에 중요한 것으로 여겨지기 때문에 다소 놀랍다.
실시예 7. 비인간 영장류에서 mARC1 siRNA 분자의 생체내 효능
3개의 상이한 mARC1 siRNA 분자(이중체 번호 D-2241, D-2081, 또는 D-2258)의 효용성 및 약동학적 프로파일을 시노몰구스 원숭이에서 평가하였다. 3개의 상이한 mARC1 siRNA 분자 각각은 시노몰구스 원숭이(마카크 원숭이(Macaca fascicularis)) MARC1 유전자와 교차 반응하는 안티센스 가닥 서열을 가졌다. 치료 경험이 없는 22 내지 48개월령의 모리셔스 혈통의 암컷 시노몰구스 마카크 원숭이는 Charles River Laboratories, Inc. Research Model Services(Houston, TX)에서 공급받았다. 동물(처리군당 n = 3)에게 단일 3 mg/kg 피하(s.c.) 주사로 1X 포스페이트 완충 식염수로 제형화된 GalNAc-접합된 mARC1 siRNA 분자(이중체 번호 D-2241, D-2081, 또는 D-2258)를 견갑골 및 중등부 부위에 투여하였다. 혈청은 투약 후 다음의 시점, 즉 0.083, 0.25, 1, 2, 4, 24, 28, 96, 168, 264, 336, 456, 528, 576, 720, 864, 및 1056 시간에 수집된 전혈로부터 준비하였다. 외과적 간 생검(왼쪽 및 오른쪽 간엽당 약 100 mg 조직)을 전처리(-13일 또는 -7일) 및 투약 후 14일차 및 30일차에 마취 하에 수집하였다. 투약 후 44일차에 간 샘플을 부검에서 수집하였다.
혈청 및 간 약동학
각각의 GalNAc-접합된 mARC1 siRNA 분자의 혈청 및 간 약동학 프로파일을 확인하기 위해, 단일 3 mg/kg s.c. 용량의 mARC1 siRNA 분자로 처리한 후 다른 시점에서 수집된 혈청 및 간 샘플을 문헌[Thayer et al., Sci. Rep., Vol. 10(1): 10425, 2020]에 기재된 것과 유사한 플레이트 기반 올리고뉴클레오티드 전기화학발광(POE) 면역분석을 사용하여 각각의 mARC1 siRNA 분자(안티센스 및 센스 가닥)에 대해 분석하였다. 올리고뉴클레오티드 포획(비오틴) 및 검출(디곡시게닌) 프로브는 Qiagen Inc.(Hilden, Germany)로부터 맞춤 합성되었으며, 그 서열은 하기의 표 25에 열거되어 있다. 간 샘플을 50 mM Tris HCl, 100 nM NaCl, 0.1% Triton X100, 및 Roche 프로테아제 억제제 칵테일(11836170001)을 함유하는 용해 완충제에서 200 mg/mL의 최종 농도로 균질화하였다. 생체분석을 위해 GalNAc-mARC1 siRNA 표준을 0.13 내지 2500 ng/mL의 농도 범위에 걸쳐 혈청 또는 간 균질액에 첨가하였다. 이어서 표준 및 생물학적 샘플을 96웰 PCR 플레이트에서 1:10으로 희석하여 최종 부피 50 μL로 만들었다. 올리고뉴클레오티드 포획 및 검출 프로브는 60 mM Na2PO4(pH 7.0, 이염기성), 1 M NaCl, 5 mM EDTA, 및 0.02% Tween 20으로 구성된 혼성화 완충제에서 준비하였다. 프로브를 결합하고 10 nM의 최종 농도로 PCR 플레이트에 첨가하여 총 샘플 부피가 웰당 100 μL가 되도록 하였다. 혼성화는 90℃에서 5분, 40℃에서 30분, 및 12℃에서 최종 유지 조건으로 온도 순환기를 사용하여 수행하였다. 혼성화 후, 45 μL의 샘플을 Meso Scale Diagnostics, LLC MSD Gold 96-웰 Streptavidin SECTOR 플레이트(L15SA)로 옮기고, 진탕하면서 실온에서 30분 동안 인큐베이션하였다. 플레이트를 SerCare Life Sciences 1X KPL 면역분석 세척액(5150-0011)으로 세척하였다. 세척 후 플레이트를 ThermoFisher Scientific SuperBlock T20 TBS Blocking 완충제(37536)에 희석된 0.5 μg/mL 루테늄 표지된 항-디곡시게닌 항체 50 μL와 함께 1시간 동안 인큐베이션하였다. Meso Scale Diagnostics, LLC 1X MSD Read Buffer T(R92TC; 150 μL)를 첨가하기 전에 최종 세척을 수행하고 Meso Scale Diagnostics, LLC Meso Sector S 600 기기에서 판독하였다. mARC1 siRNA 분자의 혈청 및 간 농도는 Watson LIMS 생체분석 소프트웨어 버전 7.5(ThermoFisher Scientific)에서 4-파라미터 로지스틱 모델 및 가중치 1/Y2를 사용하여 표준 곡선에서 보간하였다. 간 농도는 200 mg/mL로 나누어 ng/mL로부터 ng/mg 단위로 변환되었다. 투약 후 0.083 내지 24시간까지의 혈청 약동학 파라미터는 Phoenix WinNonlin 소프트웨어 버전 8.3.2.116(Pharsight)에서 비구획 분석을 사용하여 확인하였다.
Figure pct00178
3개의 상이한 mARC1 siRNA 분자 각각에 대해, 안티센스 및 센스 가닥 농도에 대한 혈청 농도-시간 프로파일이 도 8a 내지 8f에 제시되어 있다. 혈청에서 평균 관찰 최대 안티센스 가닥 농도(Cmax)는 표 26에 요약된 바와 같이 투약 후 2.0 내지 4.0시간에 D-2241, D-2258, 및 D-2081에 대해 각각 511, 496, 및 321 ng/mL였다. 혈청 안티센스 가닥에 대한 용량 투여 시작부터 투약 후 24시간(AUC0-24 hour)까지의 농도 시간 곡선 아래 평균 면적은 D-2258, D-2241, 및 D-2081에 대해 각각 6399, 5040, 및 4137 h*ng/mL였다. 이중체 번호 D-2258에 대한 센스 가닥 대 안티센스 가닥의 혈청 농도 비율은 주사 부위 또는 체순환에서 발생할 수 있는 가닥 분리가 있는 이중체의 잠재적 불안정성을 나타낸다. 투여 후 14일차, 30일차, 및 44일차의 안티센스 및 센스 가닥에 대한 siRNA 간 농도가 표 27에 보고되어 있다. 14일차 간 안티센스 가닥 농도는 이중체 번호 D-2081에서 가장 컸고, D-2241와 D-2258가 그 뒤를 이었다. 혈청 약동학 프로파일과 일치하여, 이중체 번호 D-2258에 대한 센스 및 안티센스 가닥의 간 농도 비율은 가닥 분리를 나타낸다.
Figure pct00179
1Tmax = 최대 관찰 농도가 관찰된 투약 후 시간; Cmax = 투약 후 측정된 최대 관찰 농도; AUC0-24 hour = 용량 투여 시작부터 투약 후 24시간까지의 선형 사다리꼴 방법을 사용한 농도 대 시간 곡선 아래 면적. N = 처리군당 3마리의 동물.
Figure pct00180
간 mARC1 mRNA 사일런싱
3개의 GalNAc-접합된 mARC1 siRNA 분자(이중체 번호 D-2241, D-2081, 및 D-2258)를 3 mg/kg s.c. 용량 투여 후 시노몰구스 마카크 원숭이 간에서 mARC1 mRNA 수준을 녹다운하는 효능에 대해 평가하였다. RNA는 ThermoFisher Scientific MagMAX-96 Total RNA Isolation 키트(AM1830)를 사용하여 스냅 냉동된 간으로부터 정제하였고 샘플 무결성(260/280 비율) 및 RNA 농도를 ThermoFisher Scientific NanoDrop 2000 분광광도계(ND-2000)로 측정하였다. ThermoFisher Scientific의 TaqMan™ RNA-to-CT 1단계 키트(4392938)를 사용하여 1단계 역전사 중합효소 연쇄 반응(RT-PCR)을 수행하였다. 50 ng의 RNA 템플릿을 2X TaqMan RT-PCR Mix, 40X TaqMan RT Enzyme Mix, 20X mARC1 프라이머-프로브(IDT, 정방향 프라이머 5'-TTCAGGATGCGATGT CTATGC-3'(서열번호 3671), 역방향 프라이머 5'-TGCCCAAAGAGTGGTGATTT-3'(서열번호 3672), 프로브 5'-/56-FAM/AGCCGCTGG(서열번호 3673)/ZEN/AAACACT GAAGAGTT(서열번호 3674)/3IABkFQ/-3'), 및 20X 글리세르알데하이드-3-포스페이트 탈수소효소 프라이머-프로브(GAPDH; ThermoFisher Scientific, Mf04392546_g1 VIC-MGB)와 혼합하여 반응물을 96웰 PCR 플레이트에 어셈블링하였다. 다음의 조건, 즉 48°C에서 30분, 90°C에서 10분, 이어서 90°C에서 15초, 60°C에서 1분을 40 사이클로 ThermoFisher Scientific QuantStudio 7 Flex Real-Time PCR System(4485701)을 사용하여 RT-PCR을 수행하였다. 하우스키핑 유전자(GAPDH)의 농도에 대한 관심 유전자(mARC1)의 농도 비율을 취하여 각 샘플에 대한 mRNA 발현을 정규화하였다. 이어서, siRNA 투여 후(14일차, 30일차, 및 44일차) mARC1 mRNA 발현의 백분율(%)은 처리군당 각 동물 복제물에 대한 전처리(-13일 또는 -7일) 시점에 상대적으로 계산되었으며, 이는 전처리의 잔여 백분율(%)로 표시하였다. mARC1 mRNA 전사체의 사일런싱 백분율(%)은 궁극적으로 100%에서 전처리값의 잔여 백분율(%)을 제하여 계산되었다. 전처리의 잔여 mRNA 백분율(%) 및 사일런싱 백분율(%) 값 모두는 하기의 표 28에 요약되어 있다. 이중체 번호 D-2241은 시험된 가장 강력한 GalNAc-접합된 mARC1 siRNA 분자로,단일 피하 주사 후 14일차, 30일차, 및 44일차에 시노몰구스 mARC1 간 mRNA를 전처리(사일런싱 80% 초과)의 잔여 20% 미만으로 감소시켰다.
Figure pct00181
ND = 검출되지 않음; SC = 피하; SD = 표준 편차; mARC1 mRNA 발현이 분석 검출 한계 미만인 샘플은 "ND"(검출되지 않음)로 표시하고 0으로 설정함.
간 mARC1 단백질 사일런싱
3 mg/kg s.c. 용량 투여 후 시노몰구스 마카크 원숭이 간에서 mARC1 단백질 수준을 녹다운하는 데 있어서 3개의 GalNAc-접합된 mARC1 siRNA 분자(이중체 번호 D-2241, D-2081, 및 D-2258)의 효능에 대해 또한 평가하였다. 스냅 냉동된 간 조직을 ThermoFisher Scientific 프로테아제 억제제 정제(A32963)를 포함하는 Boston Bioproduct NP-40 용해 완충제(BP-119)에서 200 mg/mL로 균질화하였다. 이어서, 균질액을 4°C에서 10분 동안 10,000 x g으로 회전 침강시키고 상청액을 2 mL 96 딥웰 플레이트로 옮겼다. 상청액을 실온에서 15분 동안 인큐베이션하고 1400 rpm으로 진탕시키면서, 메탄올 중 1% 트리플루오로아세트산으로 처리하였다. 침전된 단백질을 4,000 rpm으로 15분 동안 펠릿화하고 상청액을 흡인하고 펠릿을 메탄올로 2회 세척하였다. 생성된 단백질을 37°C에서 30분 동안 10 mM 트리스(2-카르복시에틸)포스핀(ThermoFisher Scientific, 77720) 및 8 M 우레아를 포함하는 용액에서 환원 및 변성하였다. 이어서 요오도아세트아미드(20 mM; ThermoFisher Scientific, A39271)를 20 mM 중탄산암모늄 완충제의 샘플에 첨가하고 실온에서 30분 동안 인큐베이션하였다. 30 μg의 트립신(ThermoFisher Scientific, A90058) 및 10 pmol의 안정한 동위원소 표지된(SIL) 펩타이드(ThermoFisher Scientific 맞춤 펩타이드; SPLFGQYFVLENPGTIK(서열번호 3675))를 첨가하여 37°C에서 밤새 트립신 분해를 수행하였다. 분해 반응을 20% 포름산으로 종결하였고, 고체상 추출(SPE) 탈염을 위해 샘플을 준비하였다(Waters Corporation, 186008052). 샘플을 로딩하기 전에, SPE 플레이트를 메탄올로 컨디셔닝하고 1% 아세토니트릴로 1회 세척하였다. 샘플을 컨디셔닝된 SPE 플레이트에 첨가하고 분석물을 70% 아세토니트릴을 사용하여 용출시켰다. 용출액을 pH 10의 10 mM 포름산 암모늄에 재현탁하고 Agilent 1260 Infinity Bio-inert Analytical-scale Fraction Collector(G5664A)에 주입하였다. Orbitrap Lumos 질량분석기(MS)와 결합된 ThermoFisher Scientific Ultimate 3000 초고성능 액체 크로마토그래피(LC) 시스템에서 분석하기 위해 분획된 샘플(11번째 분획)을 0.1% 포름산 용액에 재현탁하였다. 다음과 같이 LC 방법을 수행하였다: 3% 아세토니트릴/물, 8 μL/분에서 트래핑 및 1.0 내지 12.1분에 걸쳐 350 nL/분, 컬럼 온도 45°C로 3.0 내지 36% 아세토니트릴/물에서 분석 구배. m/z = 955.5066에서의 경표지 및 중표지된 펩타이드 SPLFGQYFVLENPGTIK(서열번호 3675) 및 m/z = 959.5137에서의 SPLFGQYFVLENPGTIK(서열번호 3675)를 각각 모니터링하는Orbitrap Fusion Lumos 기기에서 병렬 반응 모니터링 실험을 수행하였다. 이어서 데이터를 Skyline 21.1 소프트웨어(문헌[Pino LK et al. The Skyline ecosystem: Informatics for quantitative mass spectrometry proteomics. Mass Spectrom Rev. 2020 May;39(3):229-244. doi: 10.1002/mas.21540. Epub 2017 Jul 9.])로 가져오며, 여기서 각 샘플의 SPLFGQYFVLENPGTIK(서열번호 3675) 펩타이드 피크 면적을 스파이크-인된 SIL 펩타이드 SPLFGQYFVLENPGTIK(서열번호 3675)의 피크 면적으로 정규화하였다. GAPDH 하우스키핑 단백질의 측정은 동일한 시작 조직 균질액을 사용하여 수행하였고, 빙냉 아세톤으로 침전시킨 후 1250 rpm으로 10분 동안 혼합하고 3220 x g로 15분 동안 원심분리하였다. 상청액을 흡인하고 단백질 펠릿을 메탄올로 세척하고 10 μg 트립신을 함유하는 50 mM 중탄산암모늄 완충제에 용해시키고 1000 rpm으로 혼합하면서 37℃에서 밤새 분해하였다. 분해 반응을 20% 포름산으로 종결하였고, 588.61 및 743.35 m/z에서 GAPDH 펩타이드(LISWYDNEFGYSNR(서열번호 3676)를 모니터링하는 LC-MS/MS 분석을 위해 주입하였다. GAPDH 펩타이드 피크 영역을 SCIEX Analyst 소프트웨어를 사용하여 통합하였다. 하우스키핑 유전자(GAPDH)의 농도에 대해 SIL 펩타이드에 상대적으로 측정된 바와 같이, 관심 단백질(mARC1)의 농도 비율을 취하여 각 샘플에 대한 단백질 발현을 정규화하였다. 이어서, siRNA 투여 후(14일차, 30일차, 및 44일차) mARC1 단백질 발현의 백분율(%)은 처리군당 각 동물 복제물에 대한 전처리(-13일 또는 -7일) 시점에 상대적으로 계산되었으며, 이는 전처리의 잔여 백분율(%)로 표시하였다. mARC1 단백질 발현의 사일런싱 백분율(%)은 궁극적으로 100%에서 전처리값의 잔여 백분율(%)을 제하여 계산되었다. 전처리의 잔여 단백질 백분율(%) 및 사일런싱 백분율(%) 값 모두는 하기의 표 29에 요약되어 있다. 이중체 번호 D-2081은 단일 피하 주사 후 사일런싱 89 ± 0.71%로 투여 후 14일차에 시노몰구스 mARC1 간 단백질 발현에서 가장 큰 감소를 보였다. 투약 후 30일차에, 이중체 번호 D-2081 및 D-2241은 단백질 발현을 각각 사일런싱 82 ± 7.8% 및 87 ± 11%으로 전처리 잔여 20% 미만으로 감소시켰으며, 이는 투여 후 44일차까지 유지되거나 증가하였다.
Figure pct00182
N/A = 해당 없음; ND = 검출되지 않음; SC = 피하; SD = 표준 편차; mARC1 단백질 발현이 분석 검출 한계 미만인 샘플은 "ND"(검출되지 않음)로 표시하고 0으로 설정함.
본원에 논의되고 인용된 모든 간행물, 특허 및 특허 출원은 이의 전문이 본원에 참조로 포함된다. 개시된 발명은 기재된 특정 방법, 프로토콜 및 물질이 변할 수 있으므로 이들에 제한되지 않음이 이해된다. 또한, 본원에 사용된 용어가 단지 특정 구현예를 설명하는 목적을 위한 것이며 첨부된 청구범위의 범위를 제한하려는 것이 아님이 이해된다.
당업자는 본원에 기술된 본 발명의 구체적인 구현예에 대한 많은 균등물을 인식하거나, 통상적 실험만으로도 확인할 수 있을 것이다. 이러한 균등물은 하기 청구범위에 포함되는 것으로 의도된다.
SEQUENCE LISTING <110> AMGEN INC. <120> RNAi CONSTRUCTS AND METHODS FOR INHIBITING MARC1 EXPRESSION <130> A-2664-WO-PCT <150> 63/065,190 <151> 2020-08-13 <150> 63/214,016 <151> 2021-06-23 <160> 3676 <170> PatentIn version 3.5 <210> 1 <211> 7439 <212> DNA <213> Homo sapiens <400> 1 agctgagcca ccacctccca ctccccgcgc cgccccccag aaggacgcac tgctctgatt 60 ggcccggaag ggttcaggag ctgcccagcc tttgggctcg gggccaaagg ccgcaccttc 120 ccccagcggc cccgggcgac cagcgcgctc cggccttgcc gccgccacct cgcggagaag 180 ccagccatgg gcgccgccgg ctcctccgcg ctggcgcgct ttgtcctcct cgcgcaatcc 240 cggcccgggt ggctcggggt tgccgcgctg ggcctgaccg cggtggcgct gggggctgtc 300 gcctggcgcc gcgcatggcc cacgcggcgc cggcggctgc tgcagcaggt gggcacagtg 360 gcgcagctct ggatctaccc tgtgaaatcc tgcaaggggg tgccggtgag cgaggcggag 420 tgcacggcca tggggctgcg cagcggcaac ctgcgggaca ggttttggct tgtgatcaac 480 caggagggaa acatggttac tgctcgccag gaacctcgcc tggtcctgat ttccctgacc 540 tgcgatggtg acaccctgac tctcagtgca gcctacacaa aggacctact actgcctatc 600 aaaacgccca ccacaaatgc agtgcacaag tgcagagtgc acggcctgga gatagagggc 660 agggactgtg gcgaggccac cgcccagtgg ataaccagct tcctgaagtc acagccctac 720 cgcctggtgc acttcgagcc tcacatgcga ccgagacgtc ctcatcaaat agcagacttg 780 ttccgaccca aggaccagat tgcttactca gacaccagcc cattcttgat cctttctgag 840 gcgtcgctgg cggatctcaa ctccaggcta gagaagaaag ttaaagcaac caacttcagg 900 cccaatattg taatttcagg atgcgatgtc tatgcagagg attcttggga tgagcttctt 960 attggtgacg tggaactgaa aagggtgatg gcttgttcca gatgcatttt aaccacagtg 1020 gacccagaca ccggtgtcat gagcaggaag gaaccgctgg aaacactgaa gagttatcgc 1080 cagtgtgacc cttcagaacg aaagttatat ggaaaatcac cactctttgg gcagtatttt 1140 gtgctggaaa acccagggac catcaaagtg ggagaccctg tgtacctgct gggccagtaa 1200 tgggaaccgt atgtcctgga atattagatg ccttttaaaa atgttctcaa aaatgacaac 1260 acttgaagca tggtgtttca gaactgagac ctctacattt tctttaaatt tgtgattttc 1320 acatttttcg tcttttggac ttctggtgtc tcaatgcttc aatgtcccag tgcaaaaagt 1380 aaagaaatat agtctcaata acttagtagg acttcagtaa gtcacttaaa tgacaagaca 1440 ggattctgaa aactccccgt ttaactgatt atggaatagt tctttctcct gcttctccgt 1500 ttatctacca agagcgcaga cttgcatcct gtcactacca ctcgttagag aaagagaaga 1560 agagaaagag gaagagtggg tgggctggaa gaatatccta gaatgtgtta ttgcccctgt 1620 tcatgaggta cgcaatgaaa attaaattgc accccaaata tggctggaat gccacttccc 1680 ttttcttctc aagccccggg ctagcttttg aaatggcata aagactgagg tgaccttcag 1740 gaagcactgc agatattaat tttccataga tctggatctg gccctgctgc ttctcagaca 1800 gcattggatt tcctaaaggt gctcaggagg atggttgtgt agtcatggag gacccctgga 1860 tccttgccat tcccctcagc taatgacgga gtgctccttc tccagttccg ggtgaaaaag 1920 ttctgaattc tgtggaggag aagaaaagtg attcagtgat ttcagataga ctactgaaaa 1980 cctttaaagg gggaaaagga aagcatatgt cagttgttta aaacccaata tctatttttt 2040 aactgattgt ataactctaa gatctgatga agtatatttt ttattgccat tttgtccttt 2100 gattatattg ggaagttgac taaacttgaa aaatgttttt aaaactgtga ataaatggaa 2160 gctactttga ctagtttcag atcttactaa cttcttggca caaagttaga ctgtgaaagc 2220 tgactgaggc tgggcacagg ggctcatgcc tgtaattcca gcactttggg aggccaaggt 2280 gggagaatgg cttgagccca ggagtttgag accagcccag aaaatataat gggatcctgt 2340 cgctacaaaa tgtttttaaa atgcactcgg tgtggtggtg tgtgcctgca gtcctggcta 2400 tggctactcg ggaggatgag gtagaaggat tggttgagcc caggagcggg agattgaggc 2460 tgcagtgagt tatgattgca ccactacact ccagcctgag tgatagagtg agaccctatc 2520 tctaaaaaag aaacaggaaa aaaaaagaaa gctgactgag gtgaatgggc aaagccagta 2580 attctgacac ctgaccacag ctgggtcttc tgcataatgg acctcctcac ccacagcctc 2640 ccaggcaagc acccatgttt gaaggactat caagtcaaca tgctttttac caaaagctgc 2700 acatttttca ctttgatttt ataaaagagg tcagtaatcg ctgaaatcta gctgagccct 2760 gaagtaaagt tctgagcaaa gaggtgcatg tgcttgtttt atggttggtg aattattaca 2820 gtttgttttc tgcatgcttg gcatgaggtg aataattaca tcaattttcc agagaacctg 2880 ggccatcacc ttccccaaca agtccagttg atgttgaaac tacagataga ttgagacaaa 2940 gcgaagtgtt cagcaagtag cattactaat gggaccgggg gacccgtggg agagtgagtg 3000 tacacaggat ttaggaaacc atgtgaatat gggctctctg ggaatagcca ataggtaggg 3060 agcaatcaga aacccaaggt ttggtggctc ttcctaggta tttataatta gtggcaagtg 3120 aaagccttag tcctgaattt ctaaccactt gtaagaacta acagccactt ctctgtgccc 3180 cgtccgggca gtaaccatca ttctccatgg acaggctctc ggggtagcta gctctgcagg 3240 gcagcaccca cgtggaaggg agcacccaga aaccctcctc actgggcaga cctgtccttc 3300 tgtgcctcac agtgtgagga agattcctgt ttgaagagag aagttccagt gacctctaga 3360 atctcagagt agttgccaag ctttctgtca gtgagattta aaggccattt acttgtgttt 3420 attttatatt taatgagttg gttaatgcca gagacaaagc tgatatccca tttattttgg 3480 atactgagca tttgcacact attccacttg aaatatagaa tcaggaatgt aggccatccc 3540 agactttcag atcttacaac agcaaatgac agatgtttga gatcaggcca aaatatccac 3600 cctcggtggg catctcctct gtgtggcaac ttatgctgca gccacagtgg ggagtcacaa 3660 actcagagct ggaggtcttg aaaaggacaa tgtgggccag gctccggagg ggctgcctaa 3720 aggcttgctt ttgtgactct cctgcagaaa atgttagaaa cttccaaccg aaagacgagg 3780 gcagcaactt atacacacga aggcagaaag aaattgggga aggggaggct gttggaattc 3840 aggccgttgt cctataggga gaaatactcc tcctctcctt ctccctttac tgataacggg 3900 gcatggtgag gagatgagct tgtgagggtc tgccagtttg gtaagagtgc atggggaggt 3960 tgggtaaatt agactagcca aatgggactt cgggaaacca tttatgaggc tgtcaccaac 4020 agtgatggca ggctgaaatt ccaggcaagt gctcccagca ttccaagagt gtatcaaatt 4080 aaagcaaccc atgatggtgg agaacagata cattaaagtt ccttgaaaat gacagagtgg 4140 ctctcagacc agaccttgat tgtgggtata atcggagtgt tgctaccaca ccctaacact 4200 gcatttcccg tgttttattg gtccatggaa ttctgaaagt ttgcctttcg ggatgcttct 4260 aaaaacaatt ccatggacca gtaagtttgg aaagtcctgc gtgcctcact tctcttcaaa 4320 ggcaaaaggc tctggagagg ccttcatgaa gacatctgtg tttaatgctg cccttcccaa 4380 aggtctgttt ttgactgtct tttgagaaat gatcctctga tctctaggca gaatgccagt 4440 gagccaagga atcccagtta gcaggagggg tgcactcatg ggaagactga agaagttaaa 4500 agttcccgcc aagtgaagga gacctatctt gggacacttc cccttgtcct ctcccttgcc 4560 cctcttgctg gagtaaaagg atggaactgg gacttgatag gttaaaggag gtgtggagaa 4620 gtgtcttaga ccagctctcc tgttgtgggc cttagggaga agcactctct ttcttcggga 4680 tcattttcca aacatgcatt tttggatgga tagggtggat cagggtgagg gaagggaaac 4740 caaactctct ctaaccttgc ccttacagca atacctgtga tgtaagttac aaaaccacct 4800 gtgatgaaag tgctccagga tgcttcatgc accagggagg ggtgccctgt ttctcttctg 4860 ctagcttctc ctttcttttt tttttttctt cttttttttg agacagtgtc tcactctgtt 4920 gccaggctgg agtgcagtgg tgagatctca gctcactgca gcctctgcct cccaggttca 4980 agcaattctt ctgcctcagc ctcccgagta gctggtgtgt ctggagttgg ttccttctgg 5040 tgggttcttg gtctcgctga cttcaagaat gaagccacag accttcgcag tgagtgttac 5100 agctcttaaa ggtggcacgg acccaaagtg agcagtagca agatttattg tggagagcga 5160 aagaacaaag cttcggaagg ggacccaaat gggctgctgc tgctggctgg ggtggccacc 5220 ttttattccc ttatttgtcc ctgcccatgt cctgctgatt gctccatttt acagagtgct 5280 gattggtcca ttttacagag tgctgattgg tgcatttaca atcctttagc tagacacaga 5340 gtgccgattg gtgagttttt acagtgctga ttggtgcatt tacaatcctt tagctagaca 5400 cagaacactg actggtgcat ttataatcct ctagctagaa agaaaagttc tccaagtccc 5460 cactagaccc aggaagtcca gctggcttca cctctcactg ggactacagg tgcacaccac 5520 cacacccagc taatttttgt atttttagta gagacggggt ttcaccatgt tgttcaggat 5580 ggtctcgaac tcttgatctc gtgatctgcc cgcctcggcc tcccaaagtg ctgggattac 5640 agttgtgagc caccacgccc ggccctagct tttcctttct gttgcaagtc ctctcaacta 5700 gtgttgcctt ccaccctaca aagcagaatt acctcagaag tcctatggcc ctgactctat 5760 ctatgtctgc acaaagcact actgtgcttt gctgtctgca agaacagaga ttgtttgctt 5820 caaccacttt ctctgaatgg atgaatgagt tatgatgata tctaaagtta cccaatttca 5880 agcaagagga agaatctggc tcggtaccac agatgttctt ggaattggga tagtaaaaaa 5940 gtccctgagg catcccttgg tctgctctga ccacactctc ttcacaggaa gaggcttggg 6000 ccacagctct gactataact ctgctcttcc tccaaacaca gctgaggaat tgggtggtgg 6060 ggcacctgct cccatgctct gtggcctggc tcagagagaa gagttgcctt aattacatta 6120 ttattcttcc tggacaggct gtaggttgtg taaagtaaca aaaaggactg agaagtgact 6180 tcccattcag cctcttccaa ggccattttt gataggcagg tcaaattcac tcacatttgg 6240 ttatttgttg gccagtctag tgcattcacc cttgctggtc ctcagtcatg ctcctttacc 6300 tttacagagc atcctagact gctcttcctc ttaccttcct tgtgaaaccc acaaccccta 6360 gtccctcccc ttccctggca tttgttatgc cctctaccaa tccctgacct ggtattggtc 6420 agtctccaat cctggtggat ccctgtggga actaagttaa gtctaacttt tgtctccctc 6480 tttagaattt actgggagta ctgtaaataa actattgttg ttataattat ttctgattaa 6540 catttttaca cctaacaaag tctcagagag attgaattta ctgggttgaa gggaggagca 6600 ccttccacat gacctgccca gcaattaaag ccgcttgtta gtccgaggcc caggacggcc 6660 gaggacagct ggagagctct tcgttgcagg cagctctggt taacatcaac cgggaaagct 6720 ctttgtaaac acatgaataa ttgatcgtcc agcgctcaca tagctaccgc ggatctgagc 6780 ccgtatgact catttgcgag ccattcctgt cgtctggatg ccataacatt ggaggaatga 6840 tgatcgtttc ttggaggttc ttctgtggcc agagttgcca agaccaaggc tgtaatggtt 6900 tgttatgatg acctttgtta ttccattagg ctcaattgct ttaaaaaatg atgtgtgcat 6960 actttaggaa cgtttttacc ctttatgttg acctgacatc atagtttata ttataaaatg 7020 tattaatgac agaagagtgt tttcatgtcc caaggacaaa ttttaacaac cataatctgc 7080 cctcagtcat cataaatata aatgtattgg tcaaacagat ctcgttaatg tggccaagat 7140 aaatgcaagt ctatatttta aggcagtcga agtcctagag aatatatctg gagcttttgt 7200 ggggctaaga gatcttgtat atatgctatc aaaaggctga gaaaattaac atgttccccc 7260 ctctgatttt gcattggaca gatataaatg tcttggggat gtcaagtaag attgttcaca 7320 tagtttctgg acaccattaa tgcctgatgg ggtgaatctt agttcttaaa gctatattct 7380 gctcattatg ctcacagggc ttttgaaaag agaacaaaat aaagatttca agtcttagc 7439 <210> 2 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2 gagcaagcac uauauggaau 20 <210> 3 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3 agaaguucuc ggcaaaugau 20 <210> 4 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 4 gagcaagcug aauuuggaau 20 <210> 5 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 5 agaaguucag cgcuaaugau 20 <210> 6 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 6 gaaggacgca cugcucugau 20 <210> 7 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 7 aggacgcacu gcucugauug 20 <210> 8 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 8 ggacgcacug cucugauugg 20 <210> 9 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 9 acgcacugcu cugauuggcc 20 <210> 10 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 10 cugcucugau uggcccggaa 20 <210> 11 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 11 ugcucugauu ggcccggaag 20 <210> 12 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 12 gcucugauug gcccggaagg 20 <210> 13 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 13 cggggccaaa ggccgcaccu 20 <210> 14 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 14 ggggccaaag gccgcaccuu 20 <210> 15 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 15 gccaaaggcc gcaccuuccc 20 <210> 16 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 16 ccaaaggccg caccuucccc 20 <210> 17 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 17 cgccaccucg cggagaagcc 20 <210> 18 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 18 gccaccucgc ggagaagcca 20 <210> 19 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 19 ccaccucgcg gagaagccag 20 <210> 20 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 20 accucgcgga gaagccagcc 20 <210> 21 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 21 ugaucaacca ggagggaaac 20 <210> 22 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 22 aucaaccagg agggaaacau 20 <210> 23 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 23 ucaaccagga gggaaacaug 20 <210> 24 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 24 caaccaggag ggaaacaugg 20 <210> 25 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 25 aaccaggagg gaaacauggu 20 <210> 26 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 26 accaggaggg aaacaugguu 20 <210> 27 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 27 ugcucgccag gaaccucgcc 20 <210> 28 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 28 cucgccagga accucgccug 20 <210> 29 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 29 ggaaccucgc cugguccuga 20 <210> 30 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 30 aaccucgccu gguccugauu 20 <210> 31 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 31 accucgccug guccugauuu 20 <210> 32 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 32 ccucgccugg uccugauuuc 20 <210> 33 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 33 cucgccuggu ccugauuucc 20 <210> 34 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 34 ccugguccug auuucccuga 20 <210> 35 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 35 gacucucagu gcagccuaca 20 <210> 36 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 36 cucucagugc agccuacaca 20 <210> 37 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 37 ucucagugca gccuacacaa 20 <210> 38 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 38 cucagugcag ccuacacaaa 20 <210> 39 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 39 ucagugcagc cuacacaaag 20 <210> 40 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 40 cuaucaaaac gcccaccaca 20 <210> 41 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 41 uaucaaaacg cccaccacaa 20 <210> 42 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 42 aucaaaacgc ccaccacaaa 20 <210> 43 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 43 ucaaaacgcc caccacaaau 20 <210> 44 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 44 aaacgcccac cacaaaugca 20 <210> 45 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 45 aacgcccacc acaaaugcag 20 <210> 46 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 46 ccaguggaua accagcuucc 20 <210> 47 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 47 caguggauaa ccagcuuccu 20 <210> 48 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 48 guggauaacc agcuuccuga 20 <210> 49 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 49 gauaaccagc uuccugaagu 20 <210> 50 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 50 aucaaauagc agacuuguuc 20 <210> 51 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 51 caaauagcag acuuguuccg 20 <210> 52 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 52 aaauagcaga cuuguuccga 20 <210> 53 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 53 ugagcuucuu auuggugacg 20 <210> 54 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 54 agcuucuuau uggugacgug 20 <210> 55 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 55 gcuucuuauu ggugacgugg 20 <210> 56 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 56 uucuuauugg ugacguggaa 20 <210> 57 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 57 uuggugacgu ggaacugaaa 20 <210> 58 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 58 uggugacgug gaacugaaaa 20 <210> 59 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 59 ggugacgugg aacugaaaag 20 <210> 60 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 60 gugacgugga acugaaaagg 20 <210> 61 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 61 gcuuguucca gaugcauuuu 20 <210> 62 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 62 guuccagaug cauuuuaacc 20 <210> 63 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 63 uuccagaugc auuuuaacca 20 <210> 64 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 64 ugcauuuuaa ccacagugga 20 <210> 65 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 65 gcauuuuaac cacaguggac 20 <210> 66 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 66 ggugucauga gcaggaagga 20 <210> 67 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 67 gaaccgcugg aaacacugaa 20 <210> 68 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 68 gcuggaaaca cugaagaguu 20 <210> 69 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 69 ggaaacacug aagaguuauc 20 <210> 70 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 70 gaaacacuga agaguuaucg 20 <210> 71 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 71 aaacacugaa gaguuaucgc 20 <210> 72 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 72 aacacugaag aguuaucgcc 20 <210> 73 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 73 acacugaaga guuaucgcca 20 <210> 74 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 74 cacugaagag uuaucgccag 20 <210> 75 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 75 acugaagagu uaucgccagu 20 <210> 76 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 76 cugaagaguu aucgccagug 20 <210> 77 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 77 ugaagaguua ucgccagugu 20 <210> 78 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 78 gaagaguuau cgccagugug 20 <210> 79 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 79 gaguuaucgc cagugugacc 20 <210> 80 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 80 aguuaucgcc agugugaccc 20 <210> 81 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 81 guuaucgcca gugugacccu 20 <210> 82 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 82 uuaucgccag ugugacccuu 20 <210> 83 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 83 cgccagugug acccuucaga 20 <210> 84 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 84 gccaguguga cccuucagaa 20 <210> 85 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 85 cagugugacc cuucagaacg 20 <210> 86 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 86 agugugaccc uucagaacga 20 <210> 87 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 87 gugugacccu ucagaacgaa 20 <210> 88 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 88 ugugacccuu cagaacgaaa 20 <210> 89 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 89 gugacccuuc agaacgaaag 20 <210> 90 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 90 ugacccuuca gaacgaaagu 20 <210> 91 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 91 gacccuucag aacgaaaguu 20 <210> 92 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 92 acccuucaga acgaaaguua 20 <210> 93 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 93 cccuucagaa cgaaaguuau 20 <210> 94 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 94 ccuucagaac gaaaguuaua 20 <210> 95 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 95 cuucagaacg aaaguuauau 20 <210> 96 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 96 uucagaacga aaguuauaug 20 <210> 97 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 97 ucagaacgaa aguuauaugg 20 <210> 98 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 98 cagaacgaaa guuauaugga 20 <210> 99 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 99 aguuauaugg aaaaucacca 20 <210> 100 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 100 uuauauggaa aaucaccacu 20 <210> 101 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 101 aauagcagac uuguuccgac 20 <210> 102 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 102 auagcagacu uguuccgacc 20 <210> 103 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 103 uagcagacuu guuccgaccc 20 <210> 104 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 104 agcagacuug uuccgaccca 20 <210> 105 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 105 gcagacuugu uccgacccaa 20 <210> 106 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 106 cagacuuguu ccgacccaag 20 <210> 107 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 107 agacuuguuc cgacccaagg 20 <210> 108 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 108 gacuuguucc gacccaagga 20 <210> 109 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 109 acuuguuccg acccaaggac 20 <210> 110 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 110 cuuguuccga cccaaggacc 20 <210> 111 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 111 uuccgaccca aggaccagau 20 <210> 112 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 112 aaggaccaga uugcuuacuc 20 <210> 113 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 113 gaccagauug cuuacucaga 20 <210> 114 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 114 ccagauugcu uacucagaca 20 <210> 115 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 115 cagauugcuu acucagacac 20 <210> 116 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 116 agauugcuua cucagacacc 20 <210> 117 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 117 gauugcuuac ucagacacca 20 <210> 118 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 118 auugcuuacu cagacaccag 20 <210> 119 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 119 gcuuacucag acaccagccc 20 <210> 120 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 120 uuacucagac accagcccau 20 <210> 121 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 121 cggaucucaa cuccaggcua 20 <210> 122 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 122 ggaucucaac uccaggcuag 20 <210> 123 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 123 gaucucaacu ccaggcuaga 20 <210> 124 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 124 aucucaacuc caggcuagag 20 <210> 125 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 125 aacuccaggc uagagaagaa 20 <210> 126 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 126 agaagaaagu uaaagcaacc 20 <210> 127 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 127 gaagaaaguu aaagcaacca 20 <210> 128 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 128 aagaaaguua aagcaaccaa 20 <210> 129 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 129 agaaaguuaa agcaaccaac 20 <210> 130 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 130 gaaaguuaaa gcaaccaacu 20 <210> 131 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 131 aaaguuaaag caaccaacuu 20 <210> 132 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 132 aaguuaaagc aaccaacuuc 20 <210> 133 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 133 aguuaaagca accaacuuca 20 <210> 134 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 134 guuaaagcaa ccaacuucag 20 <210> 135 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 135 aaagcaacca acuucaggcc 20 <210> 136 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 136 agcaaccaac uucaggccca 20 <210> 137 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 137 caaccaacuu caggcccaau 20 <210> 138 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 138 aaccaacuuc aggcccaaua 20 <210> 139 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 139 ccaacuucag gcccaauauu 20 <210> 140 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 140 caacuucagg cccaauauug 20 <210> 141 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 141 acuucaggcc caauauugua 20 <210> 142 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 142 cuucaggccc aauauuguaa 20 <210> 143 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 143 uucaggccca auauuguaau 20 <210> 144 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 144 ucaggcccaa uauuguaauu 20 <210> 145 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 145 aggcccaaua uuguaauuuc 20 <210> 146 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 146 ggcccaauau uguaauuuca 20 <210> 147 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 147 gaugagcuuc uuauugguga 20 <210> 148 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 148 augagcuucu uauuggugac 20 <210> 149 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 149 auauggaaaa ucaccacucu 20 <210> 150 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 150 uauggaaaau caccacucuu 20 <210> 151 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 151 auggaaaauc accacucuuu 20 <210> 152 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 152 uggaaaauca ccacucuuug 20 <210> 153 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 153 cuggaaaacc cagggaccau 20 <210> 154 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 154 ggaaaaccca gggaccauca 20 <210> 155 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 155 gaaaacccag ggaccaucaa 20 <210> 156 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 156 cccagggacc aucaaagugg 20 <210> 157 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 157 ccagggacca ucaaaguggg 20 <210> 158 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 158 gggaccauca aagugggaga 20 <210> 159 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 159 gggagacccu guguaccugc 20 <210> 160 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 160 guaccugcug ggccaguaau 20 <210> 161 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 161 ugcugggcca guaaugggaa 20 <210> 162 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 162 aaauguucuc aaaaaugaca 20 <210> 163 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 163 aauguucuca aaaaugacaa 20 <210> 164 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 164 aaaaugacaa cacuugaagc 20 <210> 165 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 165 aaaugacaac acuugaagca 20 <210> 166 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 166 aaugacaaca cuugaagcau 20 <210> 167 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 167 ugacaacacu ugaagcaugg 20 <210> 168 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 168 gacaacacuu gaagcauggu 20 <210> 169 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 169 acaacacuug aagcauggug 20 <210> 170 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 170 cacuugaagc augguguuuc 20 <210> 171 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 171 cuugaagcau gguguuucag 20 <210> 172 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 172 cuggugucuc aaugcuucaa 20 <210> 173 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 173 uggugucuca augcuucaau 20 <210> 174 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 174 ggugucucaa ugcuucaaug 20 <210> 175 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 175 gugucucaau gcuucaaugu 20 <210> 176 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 176 ugucucaaug cuucaauguc 20 <210> 177 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 177 ucucaaugcu ucaauguccc 20 <210> 178 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 178 cucaaugcuu caauguccca 20 <210> 179 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 179 caaugcuuca augucccagu 20 <210> 180 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 180 augcuucaau gucccagugc 20 <210> 181 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 181 ugcuucaaug ucccagugca 20 <210> 182 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 182 aaugacaaga caggauucug 20 <210> 183 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 183 augacaagac aggauucuga 20 <210> 184 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 184 gacaagacag gauucugaaa 20 <210> 185 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 185 aagacaggau ucugaaaacu 20 <210> 186 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 186 acaggauucu gaaaacuccc 20 <210> 187 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 187 cccguuuaac ugauuaugga 20 <210> 188 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 188 uuuaacugau uauggaauag 20 <210> 189 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 189 uuaacugauu auggaauagu 20 <210> 190 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 190 aacugauuau ggaauaguuc 20 <210> 191 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 191 acugauuaug gaauaguucu 20 <210> 192 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 192 cugauuaugg aauaguucuu 20 <210> 193 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 193 gauuauggaa uaguucuuuc 20 <210> 194 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 194 auuauggaau aguucuuucu 20 <210> 195 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 195 uugcauccug ucacuaccac 20 <210> 196 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 196 caccccaaau auggcuggaa 20 <210> 197 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 197 ccccaaauau ggcuggaaug 20 <210> 198 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 198 cucaagcccc gggcuagcuu 20 <210> 199 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 199 ucaagccccg ggcuagcuuu 20 <210> 200 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 200 aagccccggg cuagcuuuug 20 <210> 201 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 201 agccccgggc uagcuuuuga 20 <210> 202 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 202 gccccgggcu agcuuuugaa 20 <210> 203 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 203 cccgggcuag cuuuugaaau 20 <210> 204 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 204 ggcuagcuuu ugaaauggca 20 <210> 205 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 205 auaaagacug aggugaccuu 20 <210> 206 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 206 cugcagauau uaauuuucca 20 <210> 207 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 207 gauauuaauu uuccauagau 20 <210> 208 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 208 auauuaauuu uccauagauc 20 <210> 209 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 209 uaauuuucca uagaucugga 20 <210> 210 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 210 aauuuuccau agaucuggau 20 <210> 211 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 211 auuuuccaua gaucuggauc 20 <210> 212 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 212 uuuccauaga ucuggaucug 20 <210> 213 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 213 ugcuucucag acagcauugg 20 <210> 214 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 214 gcuucucaga cagcauugga 20 <210> 215 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 215 ucagacagca uuggauuucc 20 <210> 216 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 216 cagacagcau uggauuuccu 20 <210> 217 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 217 agacagcauu ggauuuccua 20 <210> 218 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 218 uuccuaaagg ugcucaggag 20 <210> 219 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 219 aggaccccug gauccuugcc 20 <210> 220 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 220 cccuggaucc uugccauucc 20 <210> 221 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 221 cuggauccuu gccauucccc 20 <210> 222 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 222 ggauccuugc cauuccccuc 20 <210> 223 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 223 gauccuugcc auuccccuca 20 <210> 224 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 224 ccuugccauu ccccucagcu 20 <210> 225 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 225 cuugccauuc cccucagcua 20 <210> 226 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 226 gccauucccc ucagcuaaug 20 <210> 227 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 227 cauuccccuc agcuaaugac 20 <210> 228 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 228 acggagugcu ccuucuccag 20 <210> 229 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 229 gaaaaccuuu aaagggggaa 20 <210> 230 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 230 cauaugucag uuguuuaaaa 20 <210> 231 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 231 ucaguuguuu aaaacccaau 20 <210> 232 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 232 aguuguuuaa aacccaauau 20 <210> 233 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 233 aaggacgcac ugcucugauu 20 <210> 234 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 234 caagccccgg gcuagcuuuu 20 <210> 235 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 235 ccccgggcua gcuuuugaaa 20 <210> 236 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 236 gacugaggug accuucagga 20 <210> 237 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 237 uauuaauuuu ccauagaucu 20 <210> 238 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 238 uuuuccauag aucuggaucu 20 <210> 239 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 239 uucucagaca gcauuggauu 20 <210> 240 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 240 uuuccuaaag gugcucagga 20 <210> 241 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 241 ccuggauccu ugccauuccc 20 <210> 242 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 242 uccuugccau uccccucagc 20 <210> 243 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 243 ccauuccccu cagcuaauga 20 <210> 244 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 244 aaaaccuuua aagggggaaa 20 <210> 245 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 245 uuguuuaaaa cccaauaucu 20 <210> 246 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 246 cucuaagauc ugaugaagua 20 <210> 247 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 247 cuaagaucug augaaguaua 20 <210> 248 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 248 uaagaucuga ugaaguauau 20 <210> 249 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 249 aagaucugau gaaguauauu 20 <210> 250 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 250 gaugaaguau auuuuuuauu 20 <210> 251 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 251 uuuuauugcc auuuuguccu 20 <210> 252 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 252 uuuauugcca uuuuguccuu 20 <210> 253 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 253 uuauugccau uuuguccuuu 20 <210> 254 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 254 auugccauuu uguccuuuga 20 <210> 255 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 255 auauugggaa guugacuaaa 20 <210> 256 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 256 ugggaaguug acuaaacuug 20 <210> 257 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 257 gggaaguuga cuaaacuuga 20 <210> 258 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 258 ggaaguugac uaaacuugaa 20 <210> 259 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 259 acugugaaua aauggaagcu 20 <210> 260 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 260 ugaauaaaug gaagcuacuu 20 <210> 261 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 261 uaaauggaag cuacuuugac 20 <210> 262 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 262 aaauggaagc uacuuugacu 20 <210> 263 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 263 aagcuacuuu gacuaguuuc 20 <210> 264 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 264 agcuacuuug acuaguuuca 20 <210> 265 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 265 ggagugcucc uucuccaguu 20 <210> 266 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 266 aaccuuuaaa gggggaaaag 20 <210> 267 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 267 accuuuaaag ggggaaaagg 20 <210> 268 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 268 uauugccauu uuguccuuug 20 <210> 269 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 269 gaaguugacu aaacuugaaa 20 <210> 270 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 270 aaguugacua aacuugaaaa 20 <210> 271 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 271 gcuacuuuga cuaguuucag 20 <210> 272 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 272 ugacucucag ugcagccuac 20 <210> 273 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 273 acgcccacca caaaugcagu 20 <210> 274 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 274 cccaguggau aaccagcuuc 20 <210> 275 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 275 caucaaauag cagacuuguu 20 <210> 276 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 276 ucaaauagca gacuuguucc 20 <210> 277 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 277 caggcuagag aagaaaguua 20 <210> 278 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 278 aggcuagaga agaaaguuaa 20 <210> 279 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 279 accaacuuca ggcccaauau 20 <210> 280 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 280 gagcuucuua uuggugacgu 20 <210> 281 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 281 cuucuuauug gugacgugga 20 <210> 282 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 282 ucuuauuggu gacguggaac 20 <210> 283 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 283 auuggugacg uggaacugaa 20 <210> 284 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 284 cuuguuccag augcauuuua 20 <210> 285 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 285 uguuccagau gcauuuuaac 20 <210> 286 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 286 cuggaaacac ugaagaguua 20 <210> 287 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 287 uggaaacacu gaagaguuau 20 <210> 288 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 288 aagaguuauc gccaguguga 20 <210> 289 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 289 agaguuaucg ccagugugac 20 <210> 290 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 290 guuauaugga aaaucaccac 20 <210> 291 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 291 gugcuggaaa acccagggac 20 <210> 292 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 292 ugcuggaaaa cccagggacc 20 <210> 293 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 293 gcuggaaaac ccagggacca 20 <210> 294 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 294 aaaacccagg gaccaucaaa 20 <210> 295 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 295 aaacccaggg accaucaaag 20 <210> 296 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 296 aacccaggga ccaucaaagu 20 <210> 297 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 297 acccagggac caucaaagug 20 <210> 298 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 298 gugggagacc cuguguaccu 20 <210> 299 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 299 gcugggccag uaaugggaac 20 <210> 300 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 300 caaaaaugac aacacuugaa 20 <210> 301 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 301 augacaacac uugaagcaug 20 <210> 302 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 302 acuugaagca ugguguuuca 20 <210> 303 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 303 aaauuuguga uuuucacauu 20 <210> 304 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 304 aaugcuucaa ugucccagug 20 <210> 305 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 305 aaaugacaag acaggauucu 20 <210> 306 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 306 uuauggaaua guucuuucuc 20 <210> 307 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 307 uauggaauag uucuuucucc 20 <210> 308 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 308 gaauaguucu uucuccugcu 20 <210> 309 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 309 aauaguucuu ucuccugcuu 20 <210> 310 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 310 ugcauccugu cacuaccacu 20 <210> 311 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 311 gcauccuguc acuaccacuc 20 <210> 312 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 312 ccgggcuagc uuuugaaaug 20 <210> 313 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 313 cgggcuagcu uuugaaaugg 20 <210> 314 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 314 aagacugagg ugaccuucag 20 <210> 315 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 315 aggugaccuu caggaagcac 20 <210> 316 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 316 ccauagaucu ggaucuggcc 20 <210> 317 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 317 uggauuuccu aaaggugcuc 20 <210> 318 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 318 gauuuccuaa aggugcucag 20 <210> 319 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 319 uccuaaaggu gcucaggagg 20 <210> 320 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 320 uggaggaccc cuggauccuu 20 <210> 321 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 321 ggaggacccc uggauccuug 20 <210> 322 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 322 gaggaccccu ggauccuugc 20 <210> 323 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 323 cggagugcuc cuucuccagu 20 <210> 324 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 324 agaaggacgc acugcucuga 20 <210> 325 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 325 cucugauugg cccggaaggg 20 <210> 326 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 326 ucugauuggc ccggaagggu 20 <210> 327 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 327 cugauuggcc cggaaggguu 20 <210> 328 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 328 ggccaaaggc cgcaccuucc 20 <210> 329 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 329 ccucgcggag aagccagcca 20 <210> 330 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 330 ggagaagcca gccaugggcg 20 <210> 331 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 331 gagaagccag ccaugggcgc 20 <210> 332 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 332 gaucaaccag gagggaaaca 20 <210> 333 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 333 acugcucgcc aggaaccucg 20 <210> 334 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 334 ucgccaggaa ccucgccugg 20 <210> 335 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 335 gccaggaacc ucgccugguc 20 <210> 336 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 336 gaaccucgcc ugguccugau 20 <210> 337 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 337 auggugacac ccugacucuc 20 <210> 338 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 338 uggugacacc cugacucuca 20 <210> 339 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 339 gacacccuga cucucagugc 20 <210> 340 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 340 acccugacuc ucagugcagc 20 <210> 341 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 341 ccgcccagug gauaaccagc 20 <210> 342 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 342 ccgccuggug cacuucgagc 20 <210> 343 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 343 cgccuggugc acuucgagcc 20 <210> 344 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 344 gccuggugca cuucgagccu 20 <210> 345 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 345 ccuggugcac uucgagccuc 20 <210> 346 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 346 cuggugcacu ucgagccuca 20 <210> 347 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 347 uggugcacuu cgagccucac 20 <210> 348 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 348 ggugcacuuc gagccucaca 20 <210> 349 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 349 gugcacuucg agccucacau 20 <210> 350 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 350 ugcacuucga gccucacaug 20 <210> 351 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 351 gcacuucgag ccucacaugc 20 <210> 352 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 352 cacuucgagc cucacaugcg 20 <210> 353 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 353 acuucgagcc ucacaugcga 20 <210> 354 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 354 cuucgagccu cacaugcgac 20 <210> 355 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 355 uucgagccuc acaugcgacc 20 <210> 356 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 356 ucgagccuca caugcgaccg 20 <210> 357 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 357 cgagccucac augcgaccga 20 <210> 358 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 358 gccucacaug cgaccgagac 20 <210> 359 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 359 cuugauccuu ucugaggcgu 20 <210> 360 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 360 cuggcggauc ucaacuccag 20 <210> 361 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 361 uggcggaucu caacuccagg 20 <210> 362 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 362 gcgaugucua ugcagaggau 20 <210> 363 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 363 gaugucuaug cagaggauuc 20 <210> 364 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 364 ugucuaugca gaggauucuu 20 <210> 365 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 365 gucuaugcag aggauucuug 20 <210> 366 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 366 ucuaugcaga ggauucuugg 20 <210> 367 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 367 cuaugcagag gauucuuggg 20 <210> 368 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 368 ggugauggcu uguuccagau 20 <210> 369 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 369 gugauggcuu guuccagaug 20 <210> 370 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 370 uggcuuguuc cagaugcauu 20 <210> 371 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 371 cauuuuaacc acaguggacc 20 <210> 372 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 372 uuuuaaccac aguggaccca 20 <210> 373 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 373 uuuaaccaca guggacccag 20 <210> 374 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 374 caccacucuu ugggcaguau 20 <210> 375 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 375 accacucuuu gggcaguauu 20 <210> 376 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 376 cuuugggcag uauuuugugc 20 <210> 377 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 377 uuugggcagu auuuugugcu 20 <210> 378 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 378 uugggcagua uuuugugcug 20 <210> 379 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 379 ugggcaguau uuugugcugg 20 <210> 380 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 380 ggcaguauuu ugugcuggaa 20 <210> 381 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 381 uauuuugugc uggaaaaccc 20 <210> 382 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 382 auuuugugcu ggaaaaccca 20 <210> 383 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 383 accguauguc cuggaauauu 20 <210> 384 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 384 ccguaugucc uggaauauua 20 <210> 385 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 385 guauguccug gaauauuaga 20 <210> 386 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 386 uauguccugg aauauuagau 20 <210> 387 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 387 auguccugga auauuagaug 20 <210> 388 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 388 uguccuggaa uauuagaugc 20 <210> 389 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 389 guccuggaau auuagaugcc 20 <210> 390 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 390 uccuggaaua uuagaugccu 20 <210> 391 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 391 ccuggaauau uagaugccuu 20 <210> 392 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 392 cuggaauauu agaugccuuu 20 <210> 393 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 393 caugguguuu cagaacugag 20 <210> 394 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 394 augguguuuc agaacugaga 20 <210> 395 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 395 ugguguuuca gaacugagac 20 <210> 396 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 396 gguguuucag aacugagacc 20 <210> 397 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 397 gaggagaaga aaagugauuc 20 <210> 398 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 398 agaagaaaag ugauucagug 20 <210> 399 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 399 gaagaaaagu gauucaguga 20 <210> 400 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 400 gaaaagugau ucagugauuu 20 <210> 401 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 401 aaagugauuc agugauuuca 20 <210> 402 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 402 acuacugaaa accuuuaaag 20 <210> 403 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 403 uacugaaaac cuuuaaaggg 20 <210> 404 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 404 uguauaacuc uaagaucuga 20 <210> 405 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 405 uauaacucua agaucugaug 20 <210> 406 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 406 auaacucuaa gaucugauga 20 <210> 407 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 407 uaacucuaag aucugaugaa 20 <210> 408 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 408 aacucuaaga ucugaugaag 20 <210> 409 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 409 acucuaagau cugaugaagu 20 <210> 410 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 410 gauuggcccg gaaggguuca 20 <210> 411 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 411 ccuuugggcu cggggccaaa 20 <210> 412 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 412 uugggcucgg ggccaaaggc 20 <210> 413 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 413 cgcaccuucc cccagcggcc 20 <210> 414 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 414 ccgccgccac cucgcggaga 20 <210> 415 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 415 uccgcgcugg cgcgcuuugu 20 <210> 416 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 416 ccgcgcuggc gcgcuuuguc 20 <210> 417 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 417 cgcgcuggcg cgcuuugucc 20 <210> 418 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 418 cgcgcuuugu ccuccucgcg 20 <210> 419 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 419 gcgcuuuguc cuccucgcgc 20 <210> 420 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 420 cgcuuugucc uccucgcgca 20 <210> 421 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 421 gcuuuguccu ccucgcgcaa 20 <210> 422 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 422 cuuuguccuc cucgcgcaau 20 <210> 423 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 423 uuuguccucc ucgcgcaauc 20 <210> 424 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 424 uguccuccuc gcgcaauccc 20 <210> 425 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 425 guccuccucg cgcaaucccg 20 <210> 426 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 426 uccuccucgc gcaaucccgg 20 <210> 427 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 427 ccuccucgcg caaucccggc 20 <210> 428 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 428 cucgcgcaau cccggcccgg 20 <210> 429 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 429 gcgcaauccc ggcccgggug 20 <210> 430 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 430 cgcaaucccg gcccgggugg 20 <210> 431 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 431 gcaaucccgg cccggguggc 20 <210> 432 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 432 ggcccgggug gcucgggguu 20 <210> 433 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 433 gcccgggugg cucgggguug 20 <210> 434 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 434 cccggguggc ucgggguugc 20 <210> 435 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 435 ucgggguugc cgcgcugggc 20 <210> 436 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 436 gguugccgcg cugggccuga 20 <210> 437 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 437 gccgcgcugg gccugaccgc 20 <210> 438 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 438 gcgcugggcc ugaccgcggu 20 <210> 439 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 439 ugggccugac cgcgguggcg 20 <210> 440 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 440 gggccugacc gcgguggcgc 20 <210> 441 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 441 gagggaaaca ugguuacugc 20 <210> 442 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 442 ggaaacaugg uuacugcucg 20 <210> 443 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 443 gaaacauggu uacugcucgc 20 <210> 444 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 444 aaacaugguu acugcucgcc 20 <210> 445 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 445 aacaugguua cugcucgcca 20 <210> 446 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 446 acaugguuac ugcucgccag 20 <210> 447 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 447 guuacugcuc gccaggaacc 20 <210> 448 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 448 uucccugacc ugcgauggug 20 <210> 449 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 449 accugcgaug gugacacccu 20 <210> 450 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 450 gugcagccua cacaaaggac 20 <210> 451 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 451 ugcagccuac acaaaggacc 20 <210> 452 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 452 cagccuacac aaaggaccua 20 <210> 453 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 453 agccuacaca aaggaccuac 20 <210> 454 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 454 gccuacacaa aggaccuacu 20 <210> 455 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 455 ccuacacaaa ggaccuacua 20 <210> 456 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 456 cuacacaaag gaccuacuac 20 <210> 457 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 457 cacaaaggac cuacuacugc 20 <210> 458 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 458 aggaccuacu acugccuauc 20 <210> 459 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 459 ggaccuacua cugccuauca 20 <210> 460 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 460 accuacuacu gccuaucaaa 20 <210> 461 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 461 uacuacugcc uaucaaaacg 20 <210> 462 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 462 cuacugccua ucaaaacgcc 20 <210> 463 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 463 gccuaucaaa acgcccacca 20 <210> 464 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 464 accacaaaug cagugcacaa 20 <210> 465 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 465 cacaaaugca gugcacaagu 20 <210> 466 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 466 caaaugcagu gcacaagugc 20 <210> 467 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 467 augcagugca caagugcaga 20 <210> 468 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 468 agugcacaag ugcagagugc 20 <210> 469 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 469 acaagugcag agugcacggc 20 <210> 470 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 470 caagugcaga gugcacggcc 20 <210> 471 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 471 ugcagagugc acggccugga 20 <210> 472 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 472 agagugcacg gccuggagau 20 <210> 473 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 473 gagugcacgg ccuggagaua 20 <210> 474 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 474 uggagauaga gggcagggac 20 <210> 475 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 475 uccugaaguc acagcccuac 20 <210> 476 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 476 cugaagucac agcccuaccg 20 <210> 477 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 477 gaagucacag cccuaccgcc 20 <210> 478 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 478 ccucacaugc gaccgagacg 20 <210> 479 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 479 cucacaugcg accgagacgu 20 <210> 480 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 480 ucacaugcga ccgagacguc 20 <210> 481 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 481 cacaugcgac cgagacgucc 20 <210> 482 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 482 acaugcgacc gagacguccu 20 <210> 483 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 483 ugcgaccgag acguccucau 20 <210> 484 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 484 gcgaccgaga cguccucauc 20 <210> 485 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 485 ccgagacguc cucaucaaau 20 <210> 486 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 486 cgagacgucc ucaucaaaua 20 <210> 487 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 487 agacguccuc aucaaauagc 20 <210> 488 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 488 uccucaucaa auagcagacu 20 <210> 489 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 489 cucaucaaau agcagacuug 20 <210> 490 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 490 cagacaccag cccauucuug 20 <210> 491 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 491 agacaccagc ccauucuuga 20 <210> 492 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 492 gacaccagcc cauucuugau 20 <210> 493 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 493 cagcccauuc uugauccuuu 20 <210> 494 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 494 ccauucuuga uccuuucuga 20 <210> 495 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 495 gcagaggauu cuugggauga 20 <210> 496 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 496 auucuuggga ugagcuucuu 20 <210> 497 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 497 cuugggauga gcuucuuauu 20 <210> 498 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 498 gggaugagcu ucuuauuggu 20 <210> 499 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 499 ggaugagcuu cuuauuggug 20 <210> 500 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 500 guggaacuga aaagggugau 20 <210> 501 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 501 uggaacugaa aagggugaug 20 <210> 502 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 502 gaacugaaaa gggugauggc 20 <210> 503 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 503 cugaaaaggg ugauggcuug 20 <210> 504 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 504 ugaaaagggu gauggcuugu 20 <210> 505 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 505 gaaaagggug auggcuuguu 20 <210> 506 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 506 aaaaggguga uggcuuguuc 20 <210> 507 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 507 guggacccag acaccggugu 20 <210> 508 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 508 uggacccaga caccgguguc 20 <210> 509 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 509 ggacccagac accgguguca 20 <210> 510 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 510 acccagacac cggugucaug 20 <210> 511 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 511 ccagacaccg gugucaugag 20 <210> 512 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 512 caccgguguc augagcagga 20 <210> 513 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 513 gucaugagca ggaaggaacc 20 <210> 514 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 514 augagcagga aggaaccgcu 20 <210> 515 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 515 aggaaggaac cgcuggaaac 20 <210> 516 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 516 ggaaggaacc gcuggaaaca 20 <210> 517 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 517 gaaggaaccg cuggaaacac 20 <210> 518 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 518 cugggccagu aaugggaacc 20 <210> 519 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 519 gggccaguaa ugggaaccgu 20 <210> 520 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 520 ggccaguaau gggaaccgua 20 <210> 521 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 521 gccaguaaug ggaaccguau 20 <210> 522 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 522 ccaguaaugg gaaccguaug 20 <210> 523 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 523 caguaauggg aaccguaugu 20 <210> 524 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 524 aguaauggga accguauguc 20 <210> 525 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 525 ugggaaccgu auguccugga 20 <210> 526 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 526 ggaaccguau guccuggaau 20 <210> 527 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 527 gaauauuaga ugccuuuuaa 20 <210> 528 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 528 gaugccuuuu aaaaauguuc 20 <210> 529 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 529 guuucagaac ugagaccucu 20 <210> 530 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 530 ucagaacuga gaccucuaca 20 <210> 531 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 531 acugagaccu cuacauuuuc 20 <210> 532 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 532 cugagaccuc uacauuuucu 20 <210> 533 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 533 ugagaccucu acauuuucuu 20 <210> 534 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 534 ugauuuucac auuuuucguc 20 <210> 535 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 535 gauuuucaca uuuuucgucu 20 <210> 536 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 536 auuuucacau uuuucgucuu 20 <210> 537 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 537 uuucacauuu uucgucuuuu 20 <210> 538 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 538 uucacauuuu ucgucuuuug 20 <210> 539 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 539 ucacauuuuu cgucuuuugg 20 <210> 540 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 540 acauuuuucg ucuuuuggac 20 <210> 541 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 541 uuuucgucuu uuggacuucu 20 <210> 542 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 542 uuucgucuuu uggacuucug 20 <210> 543 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 543 uucgucuuuu ggacuucugg 20 <210> 544 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 544 ucgucuuuug gacuucuggu 20 <210> 545 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 545 cuuuuggacu ucuggugucu 20 <210> 546 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 546 uuggacuucu ggugucucaa 20 <210> 547 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 547 ggacuucugg ugucucaaug 20 <210> 548 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 548 gacuucuggu gucucaaugc 20 <210> 549 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 549 uucugguguc ucaaugcuuc 20 <210> 550 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 550 gcuucaaugu cccagugcaa 20 <210> 551 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 551 augucccagu gcaaaaagua 20 <210> 552 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 552 ugucccagug caaaaaguaa 20 <210> 553 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 553 gucccagugc aaaaaguaaa 20 <210> 554 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 554 ucccagugca aaaaguaaag 20 <210> 555 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 555 agugcaaaaa guaaagaaau 20 <210> 556 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 556 aagaaauaua gucucaauaa 20 <210> 557 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 557 aaauauaguc ucaauaacuu 20 <210> 558 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 558 auauagucuc aauaacuuag 20 <210> 559 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 559 uauagucuca auaacuuagu 20 <210> 560 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 560 auagucucaa uaacuuagua 20 <210> 561 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 561 uagucucaau aacuuaguag 20 <210> 562 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 562 agucucaaua acuuaguagg 20 <210> 563 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 563 ucaauaacuu aguaggacuu 20 <210> 564 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 564 caauaacuua guaggacuuc 20 <210> 565 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 565 auaacuuagu aggacuucag 20 <210> 566 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 566 aacuuaguag gacuucagua 20 <210> 567 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 567 acuuaguagg acuucaguaa 20 <210> 568 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 568 uuaguaggac uucaguaagu 20 <210> 569 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 569 uaguaggacu ucaguaaguc 20 <210> 570 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 570 aguaggacuu caguaaguca 20 <210> 571 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 571 uaggacuuca guaagucacu 20 <210> 572 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 572 uaaaugacaa gacaggauuc 20 <210> 573 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 573 ggauucugaa aacuccccgu 20 <210> 574 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 574 gauucugaaa acuccccguu 20 <210> 575 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 575 uucugaaaac uccccguuua 20 <210> 576 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 576 ucugaaaacu ccccguuuaa 20 <210> 577 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 577 cugaaaacuc cccguuuaac 20 <210> 578 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 578 ugaaaacucc ccguuuaacu 20 <210> 579 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 579 aaaacucccc guuuaacuga 20 <210> 580 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 580 acuccccguu uaacugauua 20 <210> 581 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 581 cuccccguuu aacugauuau 20 <210> 582 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 582 uccccguuua acugauuaug 20 <210> 583 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 583 ccccguuuaa cugauuaugg 20 <210> 584 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 584 uucuccugcu ucuccguuua 20 <210> 585 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 585 ucuccugcuu cuccguuuau 20 <210> 586 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 586 cuccugcuuc uccguuuauc 20 <210> 587 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 587 ccugcuucuc cguuuaucua 20 <210> 588 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 588 gcuucuccgu uuaucuacca 20 <210> 589 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 589 cuucuccguu uaucuaccaa 20 <210> 590 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 590 uucuccguuu aucuaccaag 20 <210> 591 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 591 ucuccguuua ucuaccaaga 20 <210> 592 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 592 cuccguuuau cuaccaagag 20 <210> 593 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 593 uccguuuauc uaccaagagc 20 <210> 594 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 594 cguuuaucua ccaagagcgc 20 <210> 595 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 595 uuaucuacca agagcgcaga 20 <210> 596 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 596 aucuaccaag agcgcagacu 20 <210> 597 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 597 uaccaagagc gcagacuugc 20 <210> 598 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 598 accaagagcg cagacuugca 20 <210> 599 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 599 caagagcgca gacuugcauc 20 <210> 600 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 600 aagagcgcag acuugcaucc 20 <210> 601 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 601 gagcgcagac uugcauccug 20 <210> 602 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 602 gcgcagacuu gcauccuguc 20 <210> 603 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 603 cgcagacuug cauccuguca 20 <210> 604 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 604 cagacuugca uccugucacu 20 <210> 605 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 605 cuugcauccu gucacuacca 20 <210> 606 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 606 cauccuguca cuaccacucg 20 <210> 607 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 607 uccugucacu accacucguu 20 <210> 608 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 608 ccugucacua ccacucguua 20 <210> 609 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 609 cugucacuac cacucguuag 20 <210> 610 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 610 ugucacuacc acucguuaga 20 <210> 611 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 611 acuaccacuc guuagagaaa 20 <210> 612 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 612 aagagugggu gggcuggaag 20 <210> 613 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 613 uccuagaaug uguuauugcc 20 <210> 614 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 614 ccuagaaugu guuauugccc 20 <210> 615 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 615 aauguguuau ugccccuguu 20 <210> 616 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 616 guguuauugc cccuguucau 20 <210> 617 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 617 uuauugcccc uguucaugag 20 <210> 618 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 618 auugccccug uucaugaggu 20 <210> 619 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 619 aaugaaaauu aaauugcacc 20 <210> 620 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 620 augaaaauua aauugcaccc 20 <210> 621 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 621 aaauuaaauu gcaccccaaa 20 <210> 622 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 622 auuaaauugc accccaaaua 20 <210> 623 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 623 uuaaauugca ccccaaauau 20 <210> 624 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 624 aauugcaccc caaauauggc 20 <210> 625 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 625 auugcacccc aaauauggcu 20 <210> 626 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 626 auauggcugg aaugccacuu 20 <210> 627 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 627 uggaaugcca cuucccuuuu 20 <210> 628 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 628 uucccuuuuc uucucaagcc 20 <210> 629 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 629 ucuucucaag ccccgggcua 20 <210> 630 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 630 ucucaagccc cgggcuagcu 20 <210> 631 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 631 gcuuuugaaa uggcauaaag 20 <210> 632 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 632 uuugaaaugg cauaaagacu 20 <210> 633 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 633 aauggcauaa agacugaggu 20 <210> 634 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 634 uggcauaaag acugagguga 20 <210> 635 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 635 gcauaaagac ugaggugacc 20 <210> 636 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 636 gaagcacugc agauauuaau 20 <210> 637 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 637 cuaaaggugc ucaggaggau 20 <210> 638 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 638 aggugcucag gaggaugguu 20 <210> 639 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 639 gugcucagga ggaugguugu 20 <210> 640 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 640 gaggaugguu guguagucau 20 <210> 641 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 641 aggaugguug uguagucaug 20 <210> 642 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 642 ggaugguugu guagucaugg 20 <210> 643 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 643 uuguguaguc auggaggacc 20 <210> 644 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 644 ucauggagga ccccuggauc 20 <210> 645 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 645 auuccccuca gcuaaugacg 20 <210> 646 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 646 uuccccucag cuaaugacgg 20 <210> 647 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 647 uccccucagc uaaugacgga 20 <210> 648 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 648 ucagcuaaug acggagugcu 20 <210> 649 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 649 gaaaaaguuc ugaauucugu 20 <210> 650 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 650 aguucugaau ucuguggagg 20 <210> 651 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 651 agugauuuca gauagacuac 20 <210> 652 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 652 auuucagaua gacuacugaa 20 <210> 653 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 653 cagauagacu acugaaaacc 20 <210> 654 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 654 uagacuacug aaaaccuuua 20 <210> 655 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 655 agacuacuga aaaccuuuaa 20 <210> 656 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 656 aaggaaagca uaugucaguu 20 <210> 657 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 657 aggaaagcau augucaguug 20 <210> 658 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 658 ggaaagcaua ugucaguugu 20 <210> 659 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 659 aaagcauaug ucaguuguuu 20 <210> 660 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 660 aagcauaugu caguuguuua 20 <210> 661 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 661 agcauauguc aguuguuuaa 20 <210> 662 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 662 uaaaacccaa uaucuauuuu 20 <210> 663 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 663 aacccaauau cuauuuuuua 20 <210> 664 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 664 uuaacugauu guauaacucu 20 <210> 665 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 665 uaacugauug uauaacucua 20 <210> 666 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 666 acugauugua uaacucuaag 20 <210> 667 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 667 cugauuguau aacucuaaga 20 <210> 668 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 668 gauuguauaa cucuaagauc 20 <210> 669 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 669 gccauuuugu ccuuugauua 20 <210> 670 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 670 uguccuuuga uuauauuggg 20 <210> 671 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 671 uuccauauag ugcuugcucg g 21 <210> 672 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 672 ucauuugccg agaacuucug g 21 <210> 673 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 673 uuccaaauuc agcuugcucg g 21 <210> 674 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 674 ucauuagcgc ugaacuucug g 21 <210> 675 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 675 aaucagagca gugcguccuu cuu 23 <210> 676 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 676 acaaucagag cagugcgucc uuu 23 <210> 677 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 677 accaaucaga gcagugcguc cuu 23 <210> 678 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 678 aggccaauca gagcagugcg uuu 23 <210> 679 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 679 auuccgggcc aaucagagca guu 23 <210> 680 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 680 acuuccgggc caaucagagc auu 23 <210> 681 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 681 accuuccggg ccaaucagag cuu 23 <210> 682 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 682 aaggugcggc cuuuggcccc guu 23 <210> 683 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 683 aaaggugcgg ccuuuggccc cuu 23 <210> 684 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 684 agggaaggug cggccuuugg cuu 23 <210> 685 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 685 aggggaaggu gcggccuuug guu 23 <210> 686 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 686 uggcuucucc gcgagguggc guu 23 <210> 687 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 687 auggcuucuc cgcgaggugg cuu 23 <210> 688 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 688 acuggcuucu ccgcgaggug guu 23 <210> 689 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 689 uggcuggcuu cuccgcgagg uuu 23 <210> 690 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 690 uguuucccuc cugguugauc auu 23 <210> 691 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 691 aauguuuccc uccugguuga uuu 23 <210> 692 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 692 acauguuucc cuccugguug auu 23 <210> 693 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 693 accauguuuc ccuccugguu guu 23 <210> 694 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 694 aaccauguuu cccuccuggu uuu 23 <210> 695 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 695 uaaccauguu ucccuccugg uuu 23 <210> 696 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 696 aggcgagguu ccuggcgagc auu 23 <210> 697 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 697 acaggcgagg uuccuggcga guu 23 <210> 698 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 698 aucaggacca ggcgagguuc cuu 23 <210> 699 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 699 aaaucaggac caggcgaggu uuu 23 <210> 700 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 700 aaaaucagga ccaggcgagg uuu 23 <210> 701 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 701 agaaaucagg accaggcgag guu 23 <210> 702 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 702 aggaaaucag gaccaggcga guu 23 <210> 703 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 703 aucagggaaa ucaggaccag guu 23 <210> 704 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 704 auguaggcug cacugagagu cuu 23 <210> 705 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 705 uuguguaggc ugcacugaga guu 23 <210> 706 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 706 uuuguguagg cugcacugag auu 23 <210> 707 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 707 auuuguguag gcugcacuga guu 23 <210> 708 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 708 acuuugugua ggcugcacug auu 23 <210> 709 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 709 uugugguggg cguuuugaua guu 23 <210> 710 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 710 uuuguggugg gcguuuugau auu 23 <210> 711 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 711 auuuguggug ggcguuuuga uuu 23 <210> 712 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 712 aauuuguggu gggcguuuug auu 23 <210> 713 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 713 augcauuugu ggugggcguu uuu 23 <210> 714 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 714 acugcauuug uggugggcgu uuu 23 <210> 715 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 715 aggaagcugg uuauccacug guu 23 <210> 716 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 716 aaggaagcug guuauccacu guu 23 <210> 717 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 717 uucaggaagc ugguuaucca cuu 23 <210> 718 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 718 aacuucagga agcugguuau cuu 23 <210> 719 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 719 agaacaaguc ugcuauuuga uuu 23 <210> 720 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 720 ucggaacaag ucugcuauuu guu 23 <210> 721 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 721 aucggaacaa gucugcuauu uuu 23 <210> 722 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 722 acgucaccaa uaagaagcuc auu 23 <210> 723 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 723 acacgucacc aauaagaagc uuu 23 <210> 724 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 724 uccacgucac caauaagaag cuu 23 <210> 725 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 725 auuccacguc accaauaaga auu 23 <210> 726 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 726 uuuucaguuc cacgucacca auu 23 <210> 727 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 727 auuuucaguu ccacgucacc auu 23 <210> 728 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 728 acuuuucagu uccacgucac cuu 23 <210> 729 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 729 accuuuucag uuccacguca cuu 23 <210> 730 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 730 uaaaaugcau cuggaacaag cuu 23 <210> 731 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 731 ugguuaaaau gcaucuggaa cuu 23 <210> 732 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 732 augguuaaaa ugcaucugga auu 23 <210> 733 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 733 auccacugug guuaaaaugc auu 23 <210> 734 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 734 aguccacugu gguuaaaaug cuu 23 <210> 735 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 735 uuccuuccug cucaugacac cuu 23 <210> 736 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 736 auucaguguu uccagcgguu cuu 23 <210> 737 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 737 uaacucuuca guguuuccag cuu 23 <210> 738 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 738 agauaacucu ucaguguuuc cuu 23 <210> 739 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 739 acgauaacuc uucaguguuu cuu 23 <210> 740 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 740 agcgauaacu cuucaguguu uuu 23 <210> 741 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 741 uggcgauaac ucuucagugu uuu 23 <210> 742 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 742 auggcgauaa cucuucagug uuu 23 <210> 743 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 743 acuggcgaua acucuucagu guu 23 <210> 744 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 744 aacuggcgau aacucuucag uuu 23 <210> 745 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 745 acacuggcga uaacucuuca guu 23 <210> 746 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 746 aacacuggcg auaacucuuc auu 23 <210> 747 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 747 ucacacuggc gauaacucuu cuu 23 <210> 748 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 748 aggucacacu ggcgauaacu cuu 23 <210> 749 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 749 agggucacac uggcgauaac uuu 23 <210> 750 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 750 aagggucaca cuggcgauaa cuu 23 <210> 751 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 751 aaagggucac acuggcgaua auu 23 <210> 752 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 752 uucugaaggg ucacacuggc guu 23 <210> 753 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 753 auucugaagg gucacacugg cuu 23 <210> 754 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 754 ucguucugaa gggucacacu guu 23 <210> 755 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 755 uucguucuga agggucacac uuu 23 <210> 756 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 756 uuucguucug aagggucaca cuu 23 <210> 757 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 757 auuucguucu gaagggucac auu 23 <210> 758 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 758 acuuucguuc ugaaggguca cuu 23 <210> 759 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 759 aacuuucguu cugaaggguc auu 23 <210> 760 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 760 uaacuuucgu ucugaagggu cuu 23 <210> 761 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 761 auaacuuucg uucugaaggg uuu 23 <210> 762 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 762 uauaacuuuc guucugaagg guu 23 <210> 763 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 763 auauaacuuu cguucugaag guu 23 <210> 764 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 764 aauauaacuu ucguucugaa guu 23 <210> 765 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 765 acauauaacu uucguucuga auu 23 <210> 766 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 766 uccauauaac uuucguucug auu 23 <210> 767 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 767 uuccauauaa cuuucguucu guu 23 <210> 768 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 768 auggugauuu uccauauaac uuu 23 <210> 769 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 769 aaguggugau uuuccauaua auu 23 <210> 770 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 770 agucggaaca agucugcuau uuu 23 <210> 771 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 771 aggucggaac aagucugcua uuu 23 <210> 772 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 772 ugggucggaa caagucugcu auu 23 <210> 773 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 773 uugggucgga acaagucugc uuu 23 <210> 774 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 774 auugggucgg aacaagucug cuu 23 <210> 775 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 775 acuugggucg gaacaagucu guu 23 <210> 776 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 776 uccuuggguc ggaacaaguc uuu 23 <210> 777 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 777 auccuugggu cggaacaagu cuu 23 <210> 778 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 778 aguccuuggg ucggaacaag uuu 23 <210> 779 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 779 ugguccuugg gucggaacaa guu 23 <210> 780 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 780 aaucuggucc uugggucgga auu 23 <210> 781 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 781 ugaguaagca aucugguccu uuu 23 <210> 782 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 782 aucugaguaa gcaaucuggu cuu 23 <210> 783 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 783 augucugagu aagcaaucug guu 23 <210> 784 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 784 agugucugag uaagcaaucu guu 23 <210> 785 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 785 uggugucuga guaagcaauc uuu 23 <210> 786 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 786 auggugucug aguaagcaau cuu 23 <210> 787 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 787 acuggugucu gaguaagcaa uuu 23 <210> 788 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 788 ugggcuggug ucugaguaag cuu 23 <210> 789 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 789 aaugggcugg ugucugagua auu 23 <210> 790 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 790 auagccugga guugagaucc guu 23 <210> 791 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 791 ucuagccugg aguugagauc cuu 23 <210> 792 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 792 aucuagccug gaguugagau cuu 23 <210> 793 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 793 ucucuagccu ggaguugaga uuu 23 <210> 794 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 794 uuucuucucu agccuggagu uuu 23 <210> 795 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 795 ugguugcuuu aacuuucuuc uuu 23 <210> 796 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 796 uugguugcuu uaacuuucuu cuu 23 <210> 797 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 797 auugguugcu uuaacuuucu uuu 23 <210> 798 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 798 aguugguugc uuuaacuuuc uuu 23 <210> 799 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 799 aaguugguug cuuuaacuuu cuu 23 <210> 800 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 800 aaaguugguu gcuuuaacuu uuu 23 <210> 801 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 801 ugaaguuggu ugcuuuaacu uuu 23 <210> 802 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 802 augaaguugg uugcuuuaac uuu 23 <210> 803 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 803 acugaaguug guugcuuuaa cuu 23 <210> 804 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 804 aggccugaag uugguugcuu uuu 23 <210> 805 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 805 uugggccuga aguugguugc uuu 23 <210> 806 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 806 uauugggccu gaaguugguu guu 23 <210> 807 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 807 auauugggcc ugaaguuggu uuu 23 <210> 808 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 808 aaauauuggg ccugaaguug guu 23 <210> 809 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 809 acaauauugg gccugaaguu guu 23 <210> 810 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 810 uuacaauauu gggccugaag uuu 23 <210> 811 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 811 auuacaauau ugggccugaa guu 23 <210> 812 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 812 aauuacaaua uugggccuga auu 23 <210> 813 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 813 aaauuacaau auugggccug auu 23 <210> 814 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 814 ugaaauuaca auauugggcc uuu 23 <210> 815 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 815 augaaauuac aauauugggc cuu 23 <210> 816 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 816 aucaccaaua agaagcucau cuu 23 <210> 817 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 817 agucaccaau aagaagcuca uuu 23 <210> 818 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 818 aagaguggug auuuuccaua uuu 23 <210> 819 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 819 aaagaguggu gauuuuccau auu 23 <210> 820 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 820 aaaagagugg ugauuuucca uuu 23 <210> 821 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 821 acaaagagug gugauuuucc auu 23 <210> 822 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 822 aauggucccu ggguuuucca guu 23 <210> 823 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 823 uugauggucc cuggguuuuc cuu 23 <210> 824 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 824 uuugaugguc ccuggguuuu cuu 23 <210> 825 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 825 accacuuuga uggucccugg guu 23 <210> 826 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 826 ucccacuuug auggucccug guu 23 <210> 827 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 827 aucucccacu uugauggucc cuu 23 <210> 828 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 828 agcagguaca cagggucucc cuu 23 <210> 829 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 829 aauuacuggc ccagcaggua cuu 23 <210> 830 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 830 auucccauua cuggcccagc auu 23 <210> 831 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 831 uugucauuuu ugagaacauu uuu 23 <210> 832 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 832 auugucauuu uugagaacau uuu 23 <210> 833 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 833 ugcuucaagu guugucauuu uuu 23 <210> 834 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 834 augcuucaag uguugucauu uuu 23 <210> 835 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 835 aaugcuucaa guguugucau uuu 23 <210> 836 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 836 accaugcuuc aaguguuguc auu 23 <210> 837 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 837 aaccaugcuu caaguguugu cuu 23 <210> 838 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 838 acaccaugcu ucaaguguug uuu 23 <210> 839 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 839 ugaaacacca ugcuucaagu guu 23 <210> 840 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 840 ucugaaacac caugcuucaa guu 23 <210> 841 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 841 auugaagcau ugagacacca guu 23 <210> 842 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 842 aauugaagca uugagacacc auu 23 <210> 843 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 843 acauugaagc auugagacac cuu 23 <210> 844 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 844 aacauugaag cauugagaca cuu 23 <210> 845 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 845 agacauugaa gcauugagac auu 23 <210> 846 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 846 ugggacauug aagcauugag auu 23 <210> 847 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 847 augggacauu gaagcauuga guu 23 <210> 848 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 848 aacugggaca uugaagcauu guu 23 <210> 849 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 849 ugcacuggga cauugaagca uuu 23 <210> 850 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 850 uugcacuggg acauugaagc auu 23 <210> 851 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 851 ucagaauccu gucuugucau uuu 23 <210> 852 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 852 uucagaaucc ugucuuguca uuu 23 <210> 853 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 853 uuuucagaau ccugucuugu cuu 23 <210> 854 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 854 aaguuuucag aauccugucu uuu 23 <210> 855 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 855 agggaguuuu cagaauccug uuu 23 <210> 856 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 856 uuccauaauc aguuaaacgg guu 23 <210> 857 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 857 acuauuccau aaucaguuaa auu 23 <210> 858 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 858 aacuauucca uaaucaguua auu 23 <210> 859 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 859 agaacuauuc cauaaucagu uuu 23 <210> 860 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 860 aagaacuauu ccauaaucag uuu 23 <210> 861 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 861 aaagaacuau uccauaauca guu 23 <210> 862 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 862 agaaagaacu auuccauaau cuu 23 <210> 863 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 863 aagaaagaac uauuccauaa uuu 23 <210> 864 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 864 agugguagug acaggaugca auu 23 <210> 865 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 865 auuccagcca uauuuggggu guu 23 <210> 866 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 866 acauuccagc cauauuuggg guu 23 <210> 867 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 867 aaagcuagcc cggggcuuga guu 23 <210> 868 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 868 aaaagcuagc ccggggcuug auu 23 <210> 869 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 869 ucaaaagcua gcccggggcu uuu 23 <210> 870 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 870 uucaaaagcu agcccggggc uuu 23 <210> 871 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 871 uuucaaaagc uagcccgggg cuu 23 <210> 872 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 872 aauuucaaaa gcuagcccgg guu 23 <210> 873 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 873 augccauuuc aaaagcuagc cuu 23 <210> 874 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 874 aaaggucacc ucagucuuua uuu 23 <210> 875 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 875 auggaaaauu aauaucugca guu 23 <210> 876 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 876 aaucuaugga aaauuaauau cuu 23 <210> 877 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 877 agaucuaugg aaaauuaaua uuu 23 <210> 878 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 878 auccagaucu auggaaaauu auu 23 <210> 879 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 879 aauccagauc uauggaaaau uuu 23 <210> 880 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 880 agauccagau cuauggaaaa uuu 23 <210> 881 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 881 acagauccag aucuauggaa auu 23 <210> 882 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 882 uccaaugcug ucugagaagc auu 23 <210> 883 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 883 auccaaugcu gucugagaag cuu 23 <210> 884 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 884 aggaaaucca augcugucug auu 23 <210> 885 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 885 uaggaaaucc aaugcugucu guu 23 <210> 886 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 886 uuaggaaauc caaugcuguc uuu 23 <210> 887 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 887 acuccugagc accuuuagga auu 23 <210> 888 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 888 uggcaaggau ccaggggucc uuu 23 <210> 889 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 889 aggaauggca aggauccagg guu 23 <210> 890 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 890 aggggaaugg caaggaucca guu 23 <210> 891 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 891 ugaggggaau ggcaaggauc cuu 23 <210> 892 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 892 augaggggaa uggcaaggau cuu 23 <210> 893 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 893 uagcugaggg gaauggcaag guu 23 <210> 894 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 894 uuagcugagg ggaauggcaa guu 23 <210> 895 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 895 ucauuagcug aggggaaugg cuu 23 <210> 896 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 896 agucauuagc ugaggggaau guu 23 <210> 897 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 897 acuggagaag gagcacuccg uuu 23 <210> 898 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 898 uuucccccuu uaaagguuuu cuu 23 <210> 899 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 899 auuuuaaaca acugacauau guu 23 <210> 900 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 900 uauuggguuu uaaacaacug auu 23 <210> 901 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 901 aauauugggu uuuaaacaac uuu 23 <210> 902 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 902 aaaucagagc agugcguccu uuu 23 <210> 903 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 903 aaaaagcuag cccggggcuu guu 23 <210> 904 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 904 auuucaaaag cuagcccggg guu 23 <210> 905 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 905 uuccugaagg ucaccucagu cuu 23 <210> 906 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 906 aagaucuaug gaaaauuaau auu 23 <210> 907 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 907 aagauccaga ucuauggaaa auu 23 <210> 908 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 908 aaauccaaug cugucugaga auu 23 <210> 909 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 909 auccugagca ccuuuaggaa auu 23 <210> 910 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 910 agggaauggc aaggauccag guu 23 <210> 911 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 911 agcugagggg aauggcaagg auu 23 <210> 912 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 912 aucauuagcu gaggggaaug guu 23 <210> 913 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 913 uuuucccccu uuaaagguuu uuu 23 <210> 914 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 914 uagauauugg guuuuaaaca auu 23 <210> 915 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 915 auacuucauc agaucuuaga guu 23 <210> 916 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 916 auauacuuca ucagaucuua guu 23 <210> 917 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 917 aauauacuuc aucagaucuu auu 23 <210> 918 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 918 aaauauacuu caucagaucu uuu 23 <210> 919 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 919 aaauaaaaaa uauacuucau cuu 23 <210> 920 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 920 aaggacaaaa uggcaauaaa auu 23 <210> 921 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 921 aaaggacaaa auggcaauaa auu 23 <210> 922 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 922 aaaaggacaa aauggcaaua auu 23 <210> 923 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 923 aucaaaggac aaaauggcaa uuu 23 <210> 924 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 924 auuuagucaa cuucccaaua uuu 23 <210> 925 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 925 ucaaguuuag ucaacuuccc auu 23 <210> 926 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 926 uucaaguuua gucaacuucc cuu 23 <210> 927 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 927 uuucaaguuu agucaacuuc cuu 23 <210> 928 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 928 uagcuuccau uuauucacag uuu 23 <210> 929 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 929 aaaguagcuu ccauuuauuc auu 23 <210> 930 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 930 agucaaagua gcuuccauuu auu 23 <210> 931 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 931 uagucaaagu agcuuccauu uuu 23 <210> 932 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 932 ugaaacuagu caaaguagcu uuu 23 <210> 933 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 933 augaaacuag ucaaaguagc uuu 23 <210> 934 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 934 aaacuggaga aggagcacuc cuu 23 <210> 935 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 935 acuuuucccc cuuuaaaggu uuu 23 <210> 936 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 936 uccuuuuccc ccuuuaaagg uuu 23 <210> 937 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 937 ucaaaggaca aaauggcaau auu 23 <210> 938 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 938 uauucaaguu uagucaacuu cuu 23 <210> 939 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 939 uauuucaagu uuagucaacu uuu 23 <210> 940 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 940 ucugaaacua gucaaaguag cuu 23 <210> 941 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 941 uguaggcugc acugagaguc auu 23 <210> 942 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 942 aacugcauuu guggugggcg uuu 23 <210> 943 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 943 agaagcuggu uauccacugg guu 23 <210> 944 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 944 aaacaagucu gcuauuugau guu 23 <210> 945 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 945 aggaacaagu cugcuauuug auu 23 <210> 946 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 946 uuaacuuucu ucucuagccu guu 23 <210> 947 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 947 uuuaacuuuc uucucuagcc uuu 23 <210> 948 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 948 aauauugggc cugaaguugg uuu 23 <210> 949 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 949 aacgucacca auaagaagcu cuu 23 <210> 950 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 950 uuccacguca ccaauaagaa guu 23 <210> 951 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 951 aguuccacgu caccaauaag auu 23 <210> 952 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 952 uuucaguucc acgucaccaa uuu 23 <210> 953 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 953 uuaaaaugca ucuggaacaa guu 23 <210> 954 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 954 aguuaaaaug caucuggaac auu 23 <210> 955 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 955 auaacucuuc aguguuucca guu 23 <210> 956 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 956 aauaacucuu caguguuucc auu 23 <210> 957 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 957 aucacacugg cgauaacucu uuu 23 <210> 958 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 958 agucacacug gcgauaacuc uuu 23 <210> 959 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 959 aguggugauu uuccauauaa cuu 23 <210> 960 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 960 agucccuggg uuuuccagca cuu 23 <210> 961 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 961 uggucccugg guuuuccagc auu 23 <210> 962 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 962 auggucccug gguuuuccag cuu 23 <210> 963 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 963 auuugauggu cccuggguuu uuu 23 <210> 964 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 964 acuuugaugg ucccuggguu uuu 23 <210> 965 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 965 aacuuugaug gucccugggu uuu 23 <210> 966 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 966 acacuuugau ggucccuggg uuu 23 <210> 967 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 967 aagguacaca gggucuccca cuu 23 <210> 968 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 968 aguucccauu acuggcccag cuu 23 <210> 969 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 969 auucaagugu ugucauuuuu guu 23 <210> 970 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 970 acaugcuuca aguguuguca uuu 23 <210> 971 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 971 augaaacacc augcuucaag uuu 23 <210> 972 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 972 aaaugugaaa aucacaaauu uuu 23 <210> 973 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 973 acacugggac auugaagcau uuu 23 <210> 974 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 974 aagaauccug ucuugucauu uuu 23 <210> 975 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 975 agagaaagaa cuauuccaua auu 23 <210> 976 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 976 aggagaaaga acuauuccau auu 23 <210> 977 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 977 aagcaggaga aagaacuauu cuu 23 <210> 978 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 978 aaagcaggag aaagaacuau uuu 23 <210> 979 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 979 aagugguagu gacaggaugc auu 23 <210> 980 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 980 agagugguag ugacaggaug cuu 23 <210> 981 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 981 acauuucaaa agcuagcccg guu 23 <210> 982 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 982 accauuucaa aagcuagccc guu 23 <210> 983 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 983 acugaagguc accucagucu uuu 23 <210> 984 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 984 agugcuuccu gaaggucacc uuu 23 <210> 985 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 985 aggccagauc cagaucuaug guu 23 <210> 986 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 986 ugagcaccuu uaggaaaucc auu 23 <210> 987 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 987 acugagcacc uuuaggaaau cuu 23 <210> 988 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 988 uccuccugag caccuuuagg auu 23 <210> 989 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 989 aaaggaucca gggguccucc auu 23 <210> 990 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 990 acaaggaucc agggguccuc cuu 23 <210> 991 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 991 agcaaggauc cagggguccu cuu 23 <210> 992 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 992 aacuggagaa ggagcacucc guu 23 <210> 993 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 993 aucagagcag ugcguccuuc uuu 23 <210> 994 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 994 acccuuccgg gccaaucaga guu 23 <210> 995 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 995 aacccuuccg ggccaaucag auu 23 <210> 996 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 996 aaacccuucc gggccaauca guu 23 <210> 997 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 997 aggaaggugc ggccuuuggc cuu 23 <210> 998 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 998 auggcuggcu ucuccgcgag guu 23 <210> 999 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 999 acgcccaugg cuggcuucuc cuu 23 <210> 1000 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1000 agcgcccaug gcuggcuucu cuu 23 <210> 1001 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1001 auguuucccu ccugguugau cuu 23 <210> 1002 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1002 acgagguucc uggcgagcag uuu 23 <210> 1003 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1003 accaggcgag guuccuggcg auu 23 <210> 1004 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1004 agaccaggcg agguuccugg cuu 23 <210> 1005 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1005 aaucaggacc aggcgagguu cuu 23 <210> 1006 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1006 ugagagucag ggugucacca uuu 23 <210> 1007 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1007 augagaguca gggugucacc auu 23 <210> 1008 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1008 ugcacugaga gucagggugu cuu 23 <210> 1009 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1009 agcugcacug agagucaggg uuu 23 <210> 1010 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1010 agcugguuau ccacugggcg guu 23 <210> 1011 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1011 agcucgaagu gcaccaggcg guu 23 <210> 1012 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1012 aggcucgaag ugcaccaggc guu 23 <210> 1013 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1013 aaggcucgaa gugcaccagg cuu 23 <210> 1014 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1014 ugaggcucga agugcaccag guu 23 <210> 1015 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1015 augaggcucg aagugcacca guu 23 <210> 1016 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1016 ugugaggcuc gaagugcacc auu 23 <210> 1017 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1017 augugaggcu cgaagugcac cuu 23 <210> 1018 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1018 aaugugaggc ucgaagugca cuu 23 <210> 1019 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1019 acaugugagg cucgaagugc auu 23 <210> 1020 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1020 agcaugugag gcucgaagug cuu 23 <210> 1021 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1021 ucgcauguga ggcucgaagu guu 23 <210> 1022 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1022 aucgcaugug aggcucgaag uuu 23 <210> 1023 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1023 agucgcaugu gaggcucgaa guu 23 <210> 1024 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1024 aggucgcaug ugaggcucga auu 23 <210> 1025 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1025 ucggucgcau gugaggcucg auu 23 <210> 1026 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1026 aucggucgca ugugaggcuc guu 23 <210> 1027 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1027 agucucgguc gcaugugagg cuu 23 <210> 1028 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1028 aacgccucag aaaggaucaa guu 23 <210> 1029 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1029 acuggaguug agauccgcca guu 23 <210> 1030 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1030 accuggaguu gagauccgcc auu 23 <210> 1031 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1031 aauccucugc auagacaucg cuu 23 <210> 1032 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1032 agaauccucu gcauagacau cuu 23 <210> 1033 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1033 aaagaauccu cugcauagac auu 23 <210> 1034 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1034 acaagaaucc ucugcauaga cuu 23 <210> 1035 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1035 accaagaauc cucugcauag auu 23 <210> 1036 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1036 ucccaagaau ccucugcaua guu 23 <210> 1037 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1037 aaucuggaac aagccaucac cuu 23 <210> 1038 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1038 acaucuggaa caagccauca cuu 23 <210> 1039 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1039 aaaugcaucu ggaacaagcc auu 23 <210> 1040 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1040 agguccacug ugguuaaaau guu 23 <210> 1041 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1041 auggguccac ugugguuaaa auu 23 <210> 1042 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1042 ucugggucca cugugguuaa auu 23 <210> 1043 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1043 aauacugccc aaagaguggu guu 23 <210> 1044 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1044 aaauacugcc caaagagugg uuu 23 <210> 1045 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1045 agcacaaaau acugcccaaa guu 23 <210> 1046 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1046 aagcacaaaa uacugcccaa auu 23 <210> 1047 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1047 acagcacaaa auacugccca auu 23 <210> 1048 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1048 uccagcacaa aauacugccc auu 23 <210> 1049 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1049 uuuccagcac aaaauacugc cuu 23 <210> 1050 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1050 uggguuuucc agcacaaaau auu 23 <210> 1051 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1051 auggguuuuc cagcacaaaa uuu 23 <210> 1052 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1052 uaauauucca ggacauacgg uuu 23 <210> 1053 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1053 auaauauucc aggacauacg guu 23 <210> 1054 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1054 aucuaauauu ccaggacaua cuu 23 <210> 1055 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1055 aaucuaauau uccaggacau auu 23 <210> 1056 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1056 acaucuaaua uuccaggaca uuu 23 <210> 1057 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1057 agcaucuaau auuccaggac auu 23 <210> 1058 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1058 aggcaucuaa uauuccagga cuu 23 <210> 1059 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1059 aaggcaucua auauuccagg auu 23 <210> 1060 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1060 aaaggcaucu aauauuccag guu 23 <210> 1061 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1061 aaaaggcauc uaauauucca guu 23 <210> 1062 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1062 ucucaguucu gaaacaccau guu 23 <210> 1063 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1063 aucucaguuc ugaaacacca uuu 23 <210> 1064 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1064 agucucaguu cugaaacacc auu 23 <210> 1065 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1065 aggucucagu ucugaaacac cuu 23 <210> 1066 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1066 ugaaucacuu uucuucuccu cuu 23 <210> 1067 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1067 ucacugaauc acuuuucuuc uuu 23 <210> 1068 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1068 aucacugaau cacuuuucuu cuu 23 <210> 1069 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1069 aaaaucacug aaucacuuuu cuu 23 <210> 1070 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1070 augaaaucac ugaaucacuu uuu 23 <210> 1071 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1071 acuuuaaagg uuuucaguag uuu 23 <210> 1072 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1072 acccuuuaaa gguuuucagu auu 23 <210> 1073 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1073 aucagaucuu agaguuauac auu 23 <210> 1074 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1074 ucaucagauc uuagaguuau auu 23 <210> 1075 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1075 uucaucagau cuuagaguua uuu 23 <210> 1076 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1076 auucaucaga ucuuagaguu auu 23 <210> 1077 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1077 acuucaucag aucuuagagu uuu 23 <210> 1078 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1078 uacuucauca gaucuuagag uuu 23 <210> 1079 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1079 augaacccuu ccgggccaau cuu 23 <210> 1080 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1080 auuuggcccc gagcccaaag guu 23 <210> 1081 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1081 agccuuuggc cccgagccca auu 23 <210> 1082 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1082 aggccgcugg gggaaggugc guu 23 <210> 1083 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1083 uucuccgcga gguggcggcg guu 23 <210> 1084 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1084 aacaaagcgc gccagcgcgg auu 23 <210> 1085 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1085 agacaaagcg cgccagcgcg guu 23 <210> 1086 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1086 aggacaaagc gcgccagcgc guu 23 <210> 1087 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1087 acgcgaggag gacaaagcgc guu 23 <210> 1088 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1088 ugcgcgagga ggacaaagcg cuu 23 <210> 1089 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1089 uugcgcgagg aggacaaagc guu 23 <210> 1090 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1090 auugcgcgag gaggacaaag cuu 23 <210> 1091 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1091 aauugcgcga ggaggacaaa guu 23 <210> 1092 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1092 agauugcgcg aggaggacaa auu 23 <210> 1093 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1093 agggauugcg cgaggaggac auu 23 <210> 1094 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1094 acgggauugc gcgaggagga cuu 23 <210> 1095 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1095 accgggauug cgcgaggagg auu 23 <210> 1096 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1096 agccgggauu gcgcgaggag guu 23 <210> 1097 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1097 accgggccgg gauugcgcga guu 23 <210> 1098 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1098 acacccgggc cgggauugcg cuu 23 <210> 1099 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1099 accacccggg ccgggauugc guu 23 <210> 1100 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1100 agccacccgg gccgggauug cuu 23 <210> 1101 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1101 aaaccccgag ccacccgggc cuu 23 <210> 1102 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1102 acaaccccga gccacccggg cuu 23 <210> 1103 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1103 agcaaccccg agccacccgg guu 23 <210> 1104 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1104 agcccagcgc ggcaaccccg auu 23 <210> 1105 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1105 aucaggccca gcgcggcaac cuu 23 <210> 1106 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1106 agcggucagg cccagcgcgg cuu 23 <210> 1107 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1107 aaccgcgguc aggcccagcg cuu 23 <210> 1108 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1108 acgccaccgc ggucaggccc auu 23 <210> 1109 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1109 agcgccaccg cggucaggcc cuu 23 <210> 1110 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1110 agcaguaacc auguuucccu cuu 23 <210> 1111 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1111 acgagcagua accauguuuc cuu 23 <210> 1112 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1112 agcgagcagu aaccauguuu cuu 23 <210> 1113 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1113 uggcgagcag uaaccauguu uuu 23 <210> 1114 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1114 auggcgagca guaaccaugu uuu 23 <210> 1115 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1115 acuggcgagc aguaaccaug uuu 23 <210> 1116 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1116 agguuccugg cgagcaguaa cuu 23 <210> 1117 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1117 ucaccaucgc aggucaggga auu 23 <210> 1118 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1118 aaggguguca ccaucgcagg uuu 23 <210> 1119 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1119 aguccuuugu guaggcugca cuu 23 <210> 1120 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1120 agguccuuug uguaggcugc auu 23 <210> 1121 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1121 auagguccuu uguguaggcu guu 23 <210> 1122 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1122 aguagguccu uuguguaggc uuu 23 <210> 1123 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1123 uaguaggucc uuuguguagg cuu 23 <210> 1124 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1124 auaguagguc cuuuguguag guu 23 <210> 1125 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1125 aguaguaggu ccuuugugua guu 23 <210> 1126 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1126 agcaguagua gguccuuugu guu 23 <210> 1127 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1127 ugauaggcag uaguaggucc uuu 23 <210> 1128 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1128 uugauaggca guaguagguc cuu 23 <210> 1129 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1129 uuuugauagg caguaguagg uuu 23 <210> 1130 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1130 acguuuugau aggcaguagu auu 23 <210> 1131 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1131 aggcguuuug auaggcagua guu 23 <210> 1132 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1132 auggugggcg uuuugauagg cuu 23 <210> 1133 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1133 auugugcacu gcauuugugg uuu 23 <210> 1134 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1134 aacuugugca cugcauuugu guu 23 <210> 1135 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1135 ugcacuugug cacugcauuu guu 23 <210> 1136 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1136 aucugcacuu gugcacugca uuu 23 <210> 1137 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1137 ugcacucugc acuugugcac uuu 23 <210> 1138 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1138 agccgugcac ucugcacuug uuu 23 <210> 1139 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1139 aggccgugca cucugcacuu guu 23 <210> 1140 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1140 auccaggccg ugcacucugc auu 23 <210> 1141 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1141 uaucuccagg ccgugcacuc uuu 23 <210> 1142 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1142 auaucuccag gccgugcacu cuu 23 <210> 1143 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1143 agucccugcc cucuaucucc auu 23 <210> 1144 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1144 aguagggcug ugacuucagg auu 23 <210> 1145 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1145 acgguagggc ugugacuuca guu 23 <210> 1146 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1146 aggcgguagg gcugugacuu cuu 23 <210> 1147 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1147 acgucucggu cgcaugugag guu 23 <210> 1148 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1148 aacgucucgg ucgcauguga guu 23 <210> 1149 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1149 agacgucucg gucgcaugug auu 23 <210> 1150 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1150 aggacgucuc ggucgcaugu guu 23 <210> 1151 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1151 aaggacgucu cggucgcaug uuu 23 <210> 1152 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1152 aaugaggacg ucucggucgc auu 23 <210> 1153 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1153 ugaugaggac gucucggucg cuu 23 <210> 1154 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1154 uauuugauga ggacgucucg guu 23 <210> 1155 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1155 auauuugaug aggacgucuc guu 23 <210> 1156 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1156 ugcuauuuga ugaggacguc uuu 23 <210> 1157 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1157 aagucugcua uuugaugagg auu 23 <210> 1158 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1158 acaagucugc uauuugauga guu 23 <210> 1159 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1159 ucaagaaugg gcuggugucu guu 23 <210> 1160 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1160 aucaagaaug ggcugguguc uuu 23 <210> 1161 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1161 aaucaagaau gggcuggugu cuu 23 <210> 1162 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1162 aaaaggauca agaaugggcu guu 23 <210> 1163 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1163 aucagaaagg aucaagaaug guu 23 <210> 1164 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1164 aucaucccaa gaauccucug cuu 23 <210> 1165 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1165 uaagaagcuc aucccaagaa uuu 23 <210> 1166 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1166 aaauaagaag cucaucccaa guu 23 <210> 1167 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1167 aaccaauaag aagcucaucc cuu 23 <210> 1168 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1168 ucaccaauaa gaagcucauc cuu 23 <210> 1169 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1169 aaucacccuu uucaguucca cuu 23 <210> 1170 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1170 acaucacccu uuucaguucc auu 23 <210> 1171 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1171 agccaucacc cuuuucaguu cuu 23 <210> 1172 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1172 acaagccauc acccuuuuca guu 23 <210> 1173 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1173 aacaagccau cacccuuuuc auu 23 <210> 1174 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1174 aaacaagcca ucacccuuuu cuu 23 <210> 1175 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1175 agaacaagcc aucacccuuu uuu 23 <210> 1176 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1176 aacaccggug ucugggucca cuu 23 <210> 1177 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1177 ugacaccggu gucugggucc auu 23 <210> 1178 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1178 augacaccgg ugucuggguc cuu 23 <210> 1179 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1179 ucaugacacc ggugucuggg uuu 23 <210> 1180 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1180 acucaugaca ccggugucug guu 23 <210> 1181 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1181 uuccugcuca ugacaccggu guu 23 <210> 1182 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1182 agguuccuuc cugcucauga cuu 23 <210> 1183 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1183 aagcgguucc uuccugcuca uuu 23 <210> 1184 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1184 uguuuccagc gguuccuucc uuu 23 <210> 1185 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1185 auguuuccag cgguuccuuc cuu 23 <210> 1186 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1186 aguguuucca gcgguuccuu cuu 23 <210> 1187 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1187 agguucccau uacuggccca guu 23 <210> 1188 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1188 uacgguuccc auuacuggcc cuu 23 <210> 1189 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1189 auacgguucc cauuacuggc cuu 23 <210> 1190 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1190 aauacgguuc ccauuacugg cuu 23 <210> 1191 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1191 acauacgguu cccauuacug guu 23 <210> 1192 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1192 aacauacggu ucccauuacu guu 23 <210> 1193 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1193 agacauacgg uucccauuac uuu 23 <210> 1194 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1194 uuccaggaca uacgguuccc auu 23 <210> 1195 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1195 uauuccagga cauacgguuc cuu 23 <210> 1196 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1196 uuuaaaaggc aucuaauauu cuu 23 <210> 1197 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1197 agaacauuuu uaaaaggcau cuu 23 <210> 1198 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1198 uagaggucuc aguucugaaa cuu 23 <210> 1199 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1199 auguagaggu cucaguucug auu 23 <210> 1200 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1200 agaaaaugua gaggucucag uuu 23 <210> 1201 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1201 aagaaaaugu agaggucuca guu 23 <210> 1202 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1202 aaagaaaaug uagaggucuc auu 23 <210> 1203 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1203 agacgaaaaa ugugaaaauc auu 23 <210> 1204 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1204 aagacgaaaa augugaaaau cuu 23 <210> 1205 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1205 aaagacgaaa aaugugaaaa uuu 23 <210> 1206 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1206 aaaaagacga aaaaugugaa auu 23 <210> 1207 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1207 acaaaagacg aaaaauguga auu 23 <210> 1208 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1208 uccaaaagac gaaaaaugug auu 23 <210> 1209 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1209 aguccaaaag acgaaaaaug uuu 23 <210> 1210 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1210 aagaagucca aaagacgaaa auu 23 <210> 1211 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1211 acagaagucc aaaagacgaa auu 23 <210> 1212 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1212 accagaaguc caaaagacga auu 23 <210> 1213 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1213 aaccagaagu ccaaaagacg auu 23 <210> 1214 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1214 aagacaccag aaguccaaaa guu 23 <210> 1215 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1215 auugagacac cagaagucca auu 23 <210> 1216 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1216 acauugagac accagaaguc cuu 23 <210> 1217 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1217 agcauugaga caccagaagu cuu 23 <210> 1218 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1218 ugaagcauug agacaccaga auu 23 <210> 1219 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1219 uuugcacugg gacauugaag cuu 23 <210> 1220 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1220 uuacuuuuug cacugggaca uuu 23 <210> 1221 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1221 uuuacuuuuu gcacugggac auu 23 <210> 1222 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1222 auuuacuuuu ugcacuggga cuu 23 <210> 1223 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1223 ucuuuacuuu uugcacuggg auu 23 <210> 1224 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1224 uauuucuuua cuuuuugcac uuu 23 <210> 1225 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1225 auuauugaga cuauauuucu uuu 23 <210> 1226 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1226 uaaguuauug agacuauauu uuu 23 <210> 1227 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1227 acuaaguuau ugagacuaua uuu 23 <210> 1228 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1228 uacuaaguua uugagacuau auu 23 <210> 1229 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1229 auacuaaguu auugagacua uuu 23 <210> 1230 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1230 acuacuaagu uauugagacu auu 23 <210> 1231 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1231 uccuacuaag uuauugagac uuu 23 <210> 1232 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1232 aaaguccuac uaaguuauug auu 23 <210> 1233 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1233 ugaaguccua cuaaguuauu guu 23 <210> 1234 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1234 acugaagucc uacuaaguua uuu 23 <210> 1235 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1235 uuacugaagu ccuacuaagu uuu 23 <210> 1236 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1236 auuacugaag uccuacuaag uuu 23 <210> 1237 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1237 aacuuacuga aguccuacua auu 23 <210> 1238 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1238 ugacuuacug aaguccuacu auu 23 <210> 1239 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1239 augacuuacu gaaguccuac uuu 23 <210> 1240 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1240 aagugacuua cugaaguccu auu 23 <210> 1241 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1241 agaauccugu cuugucauuu auu 23 <210> 1242 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1242 aacggggagu uuucagaauc cuu 23 <210> 1243 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1243 aaacggggag uuuucagaau cuu 23 <210> 1244 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1244 uuaaacgggg aguuuucaga auu 23 <210> 1245 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1245 auuaaacggg gaguuuucag auu 23 <210> 1246 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1246 aguuaaacgg ggaguuuuca guu 23 <210> 1247 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1247 aaguuaaacg gggaguuuuc auu 23 <210> 1248 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1248 aucaguuaaa cggggaguuu uuu 23 <210> 1249 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1249 auaaucaguu aaacggggag uuu 23 <210> 1250 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1250 aauaaucagu uaaacgggga guu 23 <210> 1251 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1251 acauaaucag uuaaacgggg auu 23 <210> 1252 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1252 uccauaauca guuaaacggg guu 23 <210> 1253 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1253 auaaacggag aagcaggaga auu 23 <210> 1254 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1254 aauaaacgga gaagcaggag auu 23 <210> 1255 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1255 agauaaacgg agaagcagga guu 23 <210> 1256 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1256 auagauaaac ggagaagcag guu 23 <210> 1257 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1257 uugguagaua aacggagaag cuu 23 <210> 1258 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1258 auugguagau aaacggagaa guu 23 <210> 1259 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1259 ucuugguaga uaaacggaga auu 23 <210> 1260 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1260 aucuugguag auaaacggag auu 23 <210> 1261 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1261 acucuuggua gauaaacgga guu 23 <210> 1262 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1262 agcucuuggu agauaaacgg auu 23 <210> 1263 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1263 ugcgcucuug guagauaaac guu 23 <210> 1264 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1264 aucugcgcuc uugguagaua auu 23 <210> 1265 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1265 aagucugcgc ucuugguaga uuu 23 <210> 1266 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1266 ugcaagucug cgcucuuggu auu 23 <210> 1267 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1267 augcaagucu gcgcucuugg uuu 23 <210> 1268 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1268 agaugcaagu cugcgcucuu guu 23 <210> 1269 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1269 aggaugcaag ucugcgcucu uuu 23 <210> 1270 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1270 acaggaugca agucugcgcu cuu 23 <210> 1271 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1271 ugacaggaug caagucugcg cuu 23 <210> 1272 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1272 augacaggau gcaagucugc guu 23 <210> 1273 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1273 uagugacagg augcaagucu guu 23 <210> 1274 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1274 augguaguga caggaugcaa guu 23 <210> 1275 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1275 acgaguggua gugacaggau guu 23 <210> 1276 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1276 uaacgagugg uagugacagg auu 23 <210> 1277 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1277 auaacgagug guagugacag guu 23 <210> 1278 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1278 ucuaacgagu gguagugaca guu 23 <210> 1279 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1279 aucuaacgag ugguagugac auu 23 <210> 1280 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1280 auuucucuaa cgagugguag uuu 23 <210> 1281 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1281 ucuuccagcc cacccacucu uuu 23 <210> 1282 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1282 aggcaauaac acauucuagg auu 23 <210> 1283 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1283 agggcaauaa cacauucuag guu 23 <210> 1284 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1284 aaacaggggc aauaacacau uuu 23 <210> 1285 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1285 aaugaacagg ggcaauaaca cuu 23 <210> 1286 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1286 acucaugaac aggggcaaua auu 23 <210> 1287 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1287 uaccucauga acaggggcaa uuu 23 <210> 1288 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1288 aggugcaauu uaauuuucau uuu 23 <210> 1289 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1289 agggugcaau uuaauuuuca uuu 23 <210> 1290 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1290 auuuggggug caauuuaauu uuu 23 <210> 1291 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1291 auauuugggg ugcaauuuaa uuu 23 <210> 1292 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1292 aauauuuggg gugcaauuua auu 23 <210> 1293 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1293 agccauauuu ggggugcaau uuu 23 <210> 1294 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1294 aagccauauu uggggugcaa uuu 23 <210> 1295 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1295 aaaguggcau uccagccaua uuu 23 <210> 1296 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1296 aaaaagggaa guggcauucc auu 23 <210> 1297 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1297 aggcuugaga agaaaaggga auu 23 <210> 1298 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1298 auagcccggg gcuugagaag auu 23 <210> 1299 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1299 aagcuagccc ggggcuugag auu 23 <210> 1300 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1300 ucuuuaugcc auuucaaaag cuu 23 <210> 1301 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1301 aagucuuuau gccauuucaa auu 23 <210> 1302 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1302 aaccucaguc uuuaugccau uuu 23 <210> 1303 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1303 aucaccucag ucuuuaugcc auu 23 <210> 1304 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1304 aggucaccuc agucuuuaug cuu 23 <210> 1305 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1305 aauuaauauc ugcagugcuu cuu 23 <210> 1306 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1306 aauccuccug agcaccuuua guu 23 <210> 1307 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1307 aaaccauccu ccugagcacc uuu 23 <210> 1308 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1308 aacaaccauc cuccugagca cuu 23 <210> 1309 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1309 aaugacuaca caaccauccu cuu 23 <210> 1310 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1310 acaugacuac acaaccaucc uuu 23 <210> 1311 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1311 uccaugacua cacaaccauc cuu 23 <210> 1312 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1312 agguccucca ugacuacaca auu 23 <210> 1313 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1313 agauccaggg guccuccaug auu 23 <210> 1314 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1314 acgucauuag cugaggggaa uuu 23 <210> 1315 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1315 uccgucauua gcugagggga auu 23 <210> 1316 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1316 auccgucauu agcugagggg auu 23 <210> 1317 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1317 aagcacuccg ucauuagcug auu 23 <210> 1318 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1318 aacagaauuc agaacuuuuu cuu 23 <210> 1319 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1319 uccuccacag aauucagaac uuu 23 <210> 1320 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1320 aguagucuau cugaaaucac uuu 23 <210> 1321 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1321 uuucaguagu cuaucugaaa uuu 23 <210> 1322 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1322 agguuuucag uagucuaucu guu 23 <210> 1323 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1323 uuaaagguuu ucaguagucu auu 23 <210> 1324 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1324 uuuaaagguu uucaguaguc uuu 23 <210> 1325 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1325 aaacugacau augcuuuccu uuu 23 <210> 1326 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1326 acaacugaca uaugcuuucc uuu 23 <210> 1327 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1327 aacaacugac auaugcuuuc cuu 23 <210> 1328 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1328 uaaacaacug acauaugcuu uuu 23 <210> 1329 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1329 uuaaacaacu gacauaugcu uuu 23 <210> 1330 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1330 uuuaaacaac ugacauaugc uuu 23 <210> 1331 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1331 aaaaauagau auuggguuuu auu 23 <210> 1332 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1332 uuaaaaaaua gauauugggu uuu 23 <210> 1333 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1333 uagaguuaua caaucaguua auu 23 <210> 1334 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1334 uuagaguuau acaaucaguu auu 23 <210> 1335 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1335 ucuuagaguu auacaaucag uuu 23 <210> 1336 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1336 aucuuagagu uauacaauca guu 23 <210> 1337 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1337 agaucuuaga guuauacaau cuu 23 <210> 1338 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1338 auaaucaaag gacaaaaugg cuu 23 <210> 1339 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1339 ucccaauaua aucaaaggac auu 23 <210> 1340 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1340 gagcaagcac uauauggaau 20 <210> 1341 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1341 agaaguucuc ggcaaaugau 20 <210> 1342 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1342 gagcaagcug aauuuggaau 20 <210> 1343 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1343 agaaguucag cgcuaaugau 20 <210> 1344 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1344 gaaggacgca cugcucugau 20 <210> 1345 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1345 aggacgcacu gcucugauug 20 <210> 1346 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1346 ggacgcacug cucugauugg 20 <210> 1347 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1347 acgcacugcu cugauuggcc 20 <210> 1348 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1348 cugcucugau uggcccggaa 20 <210> 1349 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1349 ugcucugauu ggcccggaag 20 <210> 1350 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1350 gcucugauug gcccggaagg 20 <210> 1351 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1351 cggggccaaa ggccgcaccu 20 <210> 1352 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1352 ggggccaaag gccgcaccuu 20 <210> 1353 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1353 gccaaaggcc gcaccuuccc 20 <210> 1354 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1354 ccaaaggccg caccuucccc 20 <210> 1355 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1355 cgccaccucg cggagaagcc 20 <210> 1356 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1356 gccaccucgc ggagaagcca 20 <210> 1357 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1357 ccaccucgcg gagaagccag 20 <210> 1358 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1358 accucgcgga gaagccagcc 20 <210> 1359 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1359 ugaucaacca ggagggaaac 20 <210> 1360 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1360 aucaaccagg agggaaacau 20 <210> 1361 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1361 ucaaccagga gggaaacaug 20 <210> 1362 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1362 caaccaggag ggaaacaugg 20 <210> 1363 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1363 aaccaggagg gaaacauggu 20 <210> 1364 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1364 accaggaggg aaacaugguu 20 <210> 1365 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1365 ugcucgccag gaaccucgcc 20 <210> 1366 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1366 cucgccagga accucgccug 20 <210> 1367 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1367 ggaaccucgc cugguccuga 20 <210> 1368 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1368 aaccucgccu gguccugauu 20 <210> 1369 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1369 accucgccug guccugauuu 20 <210> 1370 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1370 ccucgccugg uccugauuuc 20 <210> 1371 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1371 cucgccuggu ccugauuucc 20 <210> 1372 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1372 ccugguccug auuucccuga 20 <210> 1373 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1373 gacucucagu gcagccuaca 20 <210> 1374 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1374 cucucagugc agccuacaca 20 <210> 1375 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1375 ucucagugca gccuacacaa 20 <210> 1376 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1376 cucagugcag ccuacacaaa 20 <210> 1377 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1377 ucagugcagc cuacacaaag 20 <210> 1378 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1378 cuaucaaaac gcccaccaca 20 <210> 1379 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1379 uaucaaaacg cccaccacaa 20 <210> 1380 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1380 aucaaaacgc ccaccacaaa 20 <210> 1381 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1381 ucaaaacgcc caccacaaau 20 <210> 1382 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1382 aaacgcccac cacaaaugca 20 <210> 1383 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1383 aacgcccacc acaaaugcag 20 <210> 1384 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1384 ccaguggaua accagcuucc 20 <210> 1385 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1385 caguggauaa ccagcuuccu 20 <210> 1386 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1386 guggauaacc agcuuccuga 20 <210> 1387 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1387 gauaaccagc uuccugaagu 20 <210> 1388 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1388 aucaaauagc agacuuguuc 20 <210> 1389 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1389 caaauagcag acuuguuccg 20 <210> 1390 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1390 aaauagcaga cuuguuccga 20 <210> 1391 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1391 ugagcuucuu auuggugacg 20 <210> 1392 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1392 agcuucuuau uggugacgug 20 <210> 1393 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1393 gcuucuuauu ggugacgugg 20 <210> 1394 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1394 uucuuauugg ugacguggaa 20 <210> 1395 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1395 uuggugacgu ggaacugaaa 20 <210> 1396 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1396 uggugacgug gaacugaaaa 20 <210> 1397 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1397 ggugacgugg aacugaaaag 20 <210> 1398 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1398 gugacgugga acugaaaagg 20 <210> 1399 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1399 gcuuguucca gaugcauuuu 20 <210> 1400 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1400 guuccagaug cauuuuaacc 20 <210> 1401 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1401 uuccagaugc auuuuaacca 20 <210> 1402 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1402 ugcauuuuaa ccacagugga 20 <210> 1403 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1403 gcauuuuaac cacaguggac 20 <210> 1404 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1404 ggugucauga gcaggaagga 20 <210> 1405 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1405 gaaccgcugg aaacacugaa 20 <210> 1406 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1406 gcuggaaaca cugaagaguu 20 <210> 1407 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1407 ggaaacacug aagaguuauc 20 <210> 1408 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1408 gaaacacuga agaguuaucg 20 <210> 1409 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1409 aaacacugaa gaguuaucgc 20 <210> 1410 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1410 aacacugaag aguuaucgcc 20 <210> 1411 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1411 acacugaaga guuaucgcca 20 <210> 1412 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1412 cacugaagag uuaucgccag 20 <210> 1413 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1413 acugaagagu uaucgccagu 20 <210> 1414 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1414 cugaagaguu aucgccagug 20 <210> 1415 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1415 ugaagaguua ucgccagugu 20 <210> 1416 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1416 gaagaguuau cgccagugug 20 <210> 1417 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1417 gaguuaucgc cagugugacc 20 <210> 1418 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1418 aguuaucgcc agugugaccc 20 <210> 1419 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1419 guuaucgcca gugugacccu 20 <210> 1420 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1420 uuaucgccag ugugacccuu 20 <210> 1421 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1421 cgccagugug acccuucaga 20 <210> 1422 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1422 gccaguguga cccuucagaa 20 <210> 1423 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1423 cagugugacc cuucagaacg 20 <210> 1424 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1424 agugugaccc uucagaacga 20 <210> 1425 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1425 gugugacccu ucagaacgaa 20 <210> 1426 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1426 ugugacccuu cagaacgaaa 20 <210> 1427 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1427 gugacccuuc agaacgaaag 20 <210> 1428 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1428 ugacccuuca gaacgaaagu 20 <210> 1429 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1429 gacccuucag aacgaaaguu 20 <210> 1430 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1430 acccuucaga acgaaaguua 20 <210> 1431 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1431 cccuucagaa cgaaaguuau 20 <210> 1432 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1432 ccuucagaac gaaaguuaua 20 <210> 1433 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1433 cuucagaacg aaaguuauau 20 <210> 1434 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1434 uucagaacga aaguuauaug 20 <210> 1435 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1435 ucagaacgaa aguuauaugg 20 <210> 1436 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1436 cagaacgaaa guuauaugga 20 <210> 1437 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1437 aguuauaugg aaaaucacca 20 <210> 1438 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1438 uuauauggaa aaucaccacu 20 <210> 1439 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1439 aauagcagac uuguuccgac 20 <210> 1440 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1440 auagcagacu uguuccgacc 20 <210> 1441 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1441 uagcagacuu guuccgaccc 20 <210> 1442 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1442 agcagacuug uuccgaccca 20 <210> 1443 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1443 gcagacuugu uccgacccaa 20 <210> 1444 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1444 cagacuuguu ccgacccaag 20 <210> 1445 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1445 agacuuguuc cgacccaagg 20 <210> 1446 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1446 gacuuguucc gacccaagga 20 <210> 1447 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1447 acuuguuccg acccaaggac 20 <210> 1448 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1448 cuuguuccga cccaaggacc 20 <210> 1449 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1449 uuccgaccca aggaccagau 20 <210> 1450 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1450 aaggaccaga uugcuuacuc 20 <210> 1451 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1451 gaccagauug cuuacucaga 20 <210> 1452 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1452 ccagauugcu uacucagaca 20 <210> 1453 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1453 cagauugcuu acucagacac 20 <210> 1454 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1454 agauugcuua cucagacacc 20 <210> 1455 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1455 gauugcuuac ucagacacca 20 <210> 1456 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1456 auugcuuacu cagacaccag 20 <210> 1457 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1457 gcuuacucag acaccagccc 20 <210> 1458 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1458 uuacucagac accagcccau 20 <210> 1459 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1459 cggaucucaa cuccaggcua 20 <210> 1460 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1460 ggaucucaac uccaggcuag 20 <210> 1461 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1461 gaucucaacu ccaggcuaga 20 <210> 1462 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1462 aucucaacuc caggcuagag 20 <210> 1463 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1463 aacuccaggc uagagaagaa 20 <210> 1464 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1464 agaagaaagu uaaagcaacc 20 <210> 1465 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1465 gaagaaaguu aaagcaacca 20 <210> 1466 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1466 aagaaaguua aagcaaccaa 20 <210> 1467 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1467 agaaaguuaa agcaaccaac 20 <210> 1468 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1468 gaaaguuaaa gcaaccaacu 20 <210> 1469 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1469 aaaguuaaag caaccaacuu 20 <210> 1470 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1470 aaguuaaagc aaccaacuuc 20 <210> 1471 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1471 aguuaaagca accaacuuca 20 <210> 1472 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1472 guuaaagcaa ccaacuucag 20 <210> 1473 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1473 aaagcaacca acuucaggcc 20 <210> 1474 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1474 agcaaccaac uucaggccca 20 <210> 1475 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1475 caaccaacuu caggcccaau 20 <210> 1476 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1476 aaccaacuuc aggcccaaua 20 <210> 1477 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1477 ccaacuucag gcccaauauu 20 <210> 1478 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1478 caacuucagg cccaauauug 20 <210> 1479 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1479 acuucaggcc caauauugua 20 <210> 1480 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1480 cuucaggccc aauauuguaa 20 <210> 1481 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1481 uucaggccca auauuguaau 20 <210> 1482 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <400> 1482 ucaggcccaa uauuguaauu 20 <210> 1483 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1483 aggcccaaua uuguaauuuc 20 <210> 1484 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1484 ggcccaauau uguaauuuca 20 <210> 1485 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1485 gaugagcuuc uuauugguga 20 <210> 1486 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1486 augagcuucu uauuggugac 20 <210> 1487 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1487 auauggaaaa ucaccacucu 20 <210> 1488 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1488 uauggaaaau caccacucuu 20 <210> 1489 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1489 auggaaaauc accacucuuu 20 <210> 1490 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1490 uggaaaauca ccacucuuug 20 <210> 1491 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1491 cuggaaaacc cagggaccau 20 <210> 1492 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1492 ggaaaaccca gggaccauca 20 <210> 1493 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1493 gaaaacccag ggaccaucaa 20 <210> 1494 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1494 cccagggacc aucaaagugg 20 <210> 1495 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1495 ccagggacca ucaaaguggg 20 <210> 1496 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1496 gggaccauca aagugggaga 20 <210> 1497 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1497 gggagacccu guguaccugc 20 <210> 1498 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1498 guaccugcug ggccaguaau 20 <210> 1499 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1499 ugcugggcca guaaugggaa 20 <210> 1500 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <220> <221> misc_feature <222> (1)..(20) <400> 1500 aaauguucuc aaaaaugaca 20 <210> 1501 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1501 aauguucuca aaaaugacaa 20 <210> 1502 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1502 aaaaugacaa cacuugaagc 20 <210> 1503 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1503 aaaugacaac acuugaagca 20 <210> 1504 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1504 aaugacaaca cuugaagcau 20 <210> 1505 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1505 ugacaacacu ugaagcaugg 20 <210> 1506 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1506 gacaacacuu gaagcauggu 20 <210> 1507 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1507 acaacacuug aagcauggug 20 <210> 1508 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1508 cacuugaagc augguguuuc 20 <210> 1509 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1509 cuugaagcau gguguuucag 20 <210> 1510 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1510 cuggugucuc aaugcuucaa 20 <210> 1511 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1511 uggugucuca augcuucaau 20 <210> 1512 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1512 ggugucucaa ugcuucaaug 20 <210> 1513 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1513 gugucucaau gcuucaaugu 20 <210> 1514 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1514 ugucucaaug cuucaauguc 20 <210> 1515 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1515 ucucaaugcu ucaauguccc 20 <210> 1516 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1516 cucaaugcuu caauguccca 20 <210> 1517 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1517 caaugcuuca augucccagu 20 <210> 1518 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1518 augcuucaau gucccagugc 20 <210> 1519 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1519 ugcuucaaug ucccagugca 20 <210> 1520 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1520 aaugacaaga caggauucug 20 <210> 1521 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1521 augacaagac aggauucuga 20 <210> 1522 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1522 gacaagacag gauucugaaa 20 <210> 1523 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1523 aagacaggau ucugaaaacu 20 <210> 1524 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1524 acaggauucu gaaaacuccc 20 <210> 1525 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1525 cccguuuaac ugauuaugga 20 <210> 1526 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1526 uuuaacugau uauggaauag 20 <210> 1527 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1527 uuaacugauu auggaauagu 20 <210> 1528 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1528 aacugauuau ggaauaguuc 20 <210> 1529 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1529 acugauuaug gaauaguucu 20 <210> 1530 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1530 cugauuaugg aauaguucuu 20 <210> 1531 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1531 gauuauggaa uaguucuuuc 20 <210> 1532 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1532 auuauggaau aguucuuucu 20 <210> 1533 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1533 uugcauccug ucacuaccac 20 <210> 1534 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1534 caccccaaau auggcuggaa 20 <210> 1535 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1535 ccccaaauau ggcuggaaug 20 <210> 1536 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1536 cucaagcccc gggcuagcuu 20 <210> 1537 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1537 ucaagccccg ggcuagcuuu 20 <210> 1538 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1538 aagccccggg cuagcuuuug 20 <210> 1539 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1539 agccccgggc uagcuuuuga 20 <210> 1540 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1540 gccccgggcu agcuuuugaa 20 <210> 1541 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1541 cccgggcuag cuuuugaaau 20 <210> 1542 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1542 ggcuagcuuu ugaaauggca 20 <210> 1543 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1543 auaaagacug aggugaccuu 20 <210> 1544 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1544 cugcagauau uaauuuucca 20 <210> 1545 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1545 gauauuaauu uuccauagau 20 <210> 1546 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1546 auauuaauuu uccauagauc 20 <210> 1547 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1547 uaauuuucca uagaucugga 20 <210> 1548 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1548 aauuuuccau agaucuggau 20 <210> 1549 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1549 auuuuccaua gaucuggauc 20 <210> 1550 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1550 uuuccauaga ucuggaucug 20 <210> 1551 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1551 ugcuucucag acagcauugg 20 <210> 1552 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1552 gcuucucaga cagcauugga 20 <210> 1553 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1553 ucagacagca uuggauuucc 20 <210> 1554 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1554 cagacagcau uggauuuccu 20 <210> 1555 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1555 agacagcauu ggauuuccua 20 <210> 1556 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1556 uuccuaaagg ugcucaggag 20 <210> 1557 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1557 aggaccccug gauccuugcc 20 <210> 1558 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1558 cccuggaucc uugccauucc 20 <210> 1559 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1559 cuggauccuu gccauucccc 20 <210> 1560 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1560 ggauccuugc cauuccccuc 20 <210> 1561 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1561 gauccuugcc auuccccuca 20 <210> 1562 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1562 ccuugccauu ccccucagcu 20 <210> 1563 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1563 cuugccauuc cccucagcua 20 <210> 1564 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1564 gccauucccc ucagcuaaug 20 <210> 1565 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1565 cauuccccuc agcuaaugac 20 <210> 1566 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1566 acggagugcu ccuucuccag 20 <210> 1567 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1567 gaaaaccuuu aaagggggaa 20 <210> 1568 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1568 cauaugucag uuguuuaaaa 20 <210> 1569 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1569 ucaguuguuu aaaacccaau 20 <210> 1570 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1570 aguuguuuaa aacccaauau 20 <210> 1571 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1571 aaggacgcac ugcucugauu 20 <210> 1572 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1572 caagccccgg gcuagcuuuu 20 <210> 1573 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1573 ccccgggcua gcuuuugaaa 20 <210> 1574 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1574 gacugaggug accuucagga 20 <210> 1575 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1575 uauuaauuuu ccauagaucu 20 <210> 1576 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1576 uuuuccauag aucuggaucu 20 <210> 1577 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1577 uucucagaca gcauuggauu 20 <210> 1578 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1578 uuuccuaaag gugcucagga 20 <210> 1579 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1579 ccuggauccu ugccauuccc 20 <210> 1580 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1580 uccuugccau uccccucagc 20 <210> 1581 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1581 ccauuccccu cagcuaauga 20 <210> 1582 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1582 aaaaccuuua aagggggaaa 20 <210> 1583 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1583 uuguuuaaaa cccaauaucu 20 <210> 1584 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1584 cucuaagauc ugaugaagua 20 <210> 1585 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1585 cuaagaucug augaaguaua 20 <210> 1586 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1586 uaagaucuga ugaaguauau 20 <210> 1587 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1587 aagaucugau gaaguauauu 20 <210> 1588 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1588 gaugaaguau auuuuuuauu 20 <210> 1589 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1589 uuuuauugcc auuuuguccu 20 <210> 1590 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1590 uuuauugcca uuuuguccuu 20 <210> 1591 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1591 uuauugccau uuuguccuuu 20 <210> 1592 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1592 auugccauuu uguccuuuga 20 <210> 1593 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1593 auauugggaa guugacuaaa 20 <210> 1594 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1594 ugggaaguug acuaaacuug 20 <210> 1595 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1595 gggaaguuga cuaaacuuga 20 <210> 1596 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1596 ggaaguugac uaaacuugaa 20 <210> 1597 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1597 acugugaaua aauggaagcu 20 <210> 1598 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1598 ugaauaaaug gaagcuacuu 20 <210> 1599 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1599 uaaauggaag cuacuuugac 20 <210> 1600 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1600 aaauggaagc uacuuugacu 20 <210> 1601 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1601 aagcuacuuu gacuaguuuc 20 <210> 1602 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1602 agcuacuuug acuaguuuca 20 <210> 1603 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1603 ggagugcucc uucuccaguu 20 <210> 1604 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1604 aaccuuuaaa gggggaaaag 20 <210> 1605 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1605 accuuuaaag ggggaaaagg 20 <210> 1606 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1606 uauugccauu uuguccuuug 20 <210> 1607 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1607 gaaguugacu aaacuugaaa 20 <210> 1608 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1608 aaguugacua aacuugaaaa 20 <210> 1609 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1609 gcuacuuuga cuaguuucag 20 <210> 1610 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1610 ugacucucag ugcagccuac 20 <210> 1611 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1611 acgcccacca caaaugcagu 20 <210> 1612 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1612 cccaguggau aaccagcuuc 20 <210> 1613 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1613 caucaaauag cagacuuguu 20 <210> 1614 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1614 ucaaauagca gacuuguucc 20 <210> 1615 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1615 caggcuagag aagaaaguua 20 <210> 1616 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1616 aggcuagaga agaaaguuaa 20 <210> 1617 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1617 accaacuuca ggcccaauau 20 <210> 1618 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1618 gagcuucuua uuggugacgu 20 <210> 1619 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1619 cuucuuauug gugacgugga 20 <210> 1620 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1620 ucuuauuggu gacguggaac 20 <210> 1621 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1621 auuggugacg uggaacugaa 20 <210> 1622 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1622 cuuguuccag augcauuuua 20 <210> 1623 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1623 uguuccagau gcauuuuaac 20 <210> 1624 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1624 cuggaaacac ugaagaguua 20 <210> 1625 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1625 uggaaacacu gaagaguuau 20 <210> 1626 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1626 aagaguuauc gccaguguga 20 <210> 1627 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1627 agaguuaucg ccagugugac 20 <210> 1628 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1628 guuauaugga aaaucaccac 20 <210> 1629 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 1629 gugcuggaaa acccagggac 20 <210> 1630 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1630 ugcuggaaaa cccagggacc 20 <210> 1631 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1631 gcuggaaaac ccagggacca 20 <210> 1632 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1632 aaaacccagg gaccaucaaa 20 <210> 1633 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1633 aaacccaggg accaucaaag 20 <210> 1634 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1634 aacccaggga ccaucaaagu 20 <210> 1635 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1635 acccagggac caucaaagug 20 <210> 1636 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1636 gugggagacc cuguguaccu 20 <210> 1637 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1637 gcugggccag uaaugggaac 20 <210> 1638 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1638 caaaaaugac aacacuugaa 20 <210> 1639 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1639 augacaacac uugaagcaug 20 <210> 1640 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1640 acuugaagca ugguguuuca 20 <210> 1641 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1641 aaauuuguga uuuucacauu 20 <210> 1642 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1642 aaugcuucaa ugucccagug 20 <210> 1643 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1643 aaaugacaag acaggauucu 20 <210> 1644 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1644 uuauggaaua guucuuucuc 20 <210> 1645 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1645 uauggaauag uucuuucucc 20 <210> 1646 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1646 gaauaguucu uucuccugcu 20 <210> 1647 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1647 aauaguucuu ucuccugcuu 20 <210> 1648 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1648 ugcauccugu cacuaccacu 20 <210> 1649 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1649 gcauccuguc acuaccacuc 20 <210> 1650 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1650 ccgggcuagc uuuugaaaug 20 <210> 1651 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1651 cgggcuagcu uuugaaaugg 20 <210> 1652 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1652 aagacugagg ugaccuucag 20 <210> 1653 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1653 aggugaccuu caggaagcac 20 <210> 1654 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1654 ccauagaucu ggaucuggcc 20 <210> 1655 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1655 uggauuuccu aaaggugcuc 20 <210> 1656 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1656 gauuuccuaa aggugcucag 20 <210> 1657 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1657 uccuaaaggu gcucaggagg 20 <210> 1658 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1658 uggaggaccc cuggauccuu 20 <210> 1659 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1659 ggaggacccc uggauccuug 20 <210> 1660 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1660 gaggaccccu ggauccuugc 20 <210> 1661 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1661 cggagugcuc cuucuccagu 20 <210> 1662 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1662 agaaggacgc acugcucuga 20 <210> 1663 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1663 cucugauugg cccggaaggg 20 <210> 1664 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1664 ucugauuggc ccggaagggu 20 <210> 1665 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1665 cugauuggcc cggaaggguu 20 <210> 1666 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1666 ggccaaaggc cgcaccuucc 20 <210> 1667 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1667 ccucgcggag aagccagcca 20 <210> 1668 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1668 ggagaagcca gccaugggcg 20 <210> 1669 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1669 gagaagccag ccaugggcgc 20 <210> 1670 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1670 gaucaaccag gagggaaaca 20 <210> 1671 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1671 acugcucgcc aggaaccucg 20 <210> 1672 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1672 ucgccaggaa ccucgccugg 20 <210> 1673 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1673 gccaggaacc ucgccugguc 20 <210> 1674 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1674 gaaccucgcc ugguccugau 20 <210> 1675 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1675 auggugacac ccugacucuc 20 <210> 1676 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1676 uggugacacc cugacucuca 20 <210> 1677 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1677 gacacccuga cucucagugc 20 <210> 1678 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1678 acccugacuc ucagugcagc 20 <210> 1679 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1679 ccgcccagug gauaaccagc 20 <210> 1680 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1680 ccgccuggug cacuucgagc 20 <210> 1681 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (14)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1681 cgccuggugc acuucgagcc 20 <210> 1682 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1682 gccuggugca cuucgagccu 20 <210> 1683 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1683 ccuggugcac uucgagccuc 20 <210> 1684 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1684 cuggugcacu ucgagccuca 20 <210> 1685 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1685 uggugcacuu cgagccucac 20 <210> 1686 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1686 ggugcacuuc gagccucaca 20 <210> 1687 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1687 gugcacuucg agccucacau 20 <210> 1688 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1688 ugcacuucga gccucacaug 20 <210> 1689 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1689 gcacuucgag ccucacaugc 20 <210> 1690 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1690 cacuucgagc cucacaugcg 20 <210> 1691 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1691 acuucgagcc ucacaugcga 20 <210> 1692 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1692 cuucgagccu cacaugcgac 20 <210> 1693 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1693 uucgagccuc acaugcgacc 20 <210> 1694 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1694 ucgagccuca caugcgaccg 20 <210> 1695 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1695 cgagccucac augcgaccga 20 <210> 1696 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1696 gccucacaug cgaccgagac 20 <210> 1697 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1697 cuugauccuu ucugaggcgu 20 <210> 1698 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1698 cuggcggauc ucaacuccag 20 <210> 1699 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1699 uggcggaucu caacuccagg 20 <210> 1700 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1700 gcgaugucua ugcagaggau 20 <210> 1701 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1701 gaugucuaug cagaggauuc 20 <210> 1702 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1702 ugucuaugca gaggauucuu 20 <210> 1703 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1703 gucuaugcag aggauucuug 20 <210> 1704 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1704 ucuaugcaga ggauucuugg 20 <210> 1705 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1705 cuaugcagag gauucuuggg 20 <210> 1706 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1706 ggugauggcu uguuccagau 20 <210> 1707 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1707 gugauggcuu guuccagaug 20 <210> 1708 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1708 uggcuuguuc cagaugcauu 20 <210> 1709 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1709 cauuuuaacc acaguggacc 20 <210> 1710 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1710 uuuuaaccac aguggaccca 20 <210> 1711 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1711 uuuaaccaca guggacccag 20 <210> 1712 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1712 caccacucuu ugggcaguau 20 <210> 1713 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1713 accacucuuu gggcaguauu 20 <210> 1714 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1714 cuuugggcag uauuuugugc 20 <210> 1715 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1715 uuugggcagu auuuugugcu 20 <210> 1716 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1716 uugggcagua uuuugugcug 20 <210> 1717 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1717 ugggcaguau uuugugcugg 20 <210> 1718 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1718 ggcaguauuu ugugcuggaa 20 <210> 1719 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1719 uauuuugugc uggaaaaccc 20 <210> 1720 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1720 auuuugugcu ggaaaaccca 20 <210> 1721 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1721 accguauguc cuggaauauu 20 <210> 1722 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1722 ccguaugucc uggaauauua 20 <210> 1723 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1723 guauguccug gaauauuaga 20 <210> 1724 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1724 uauguccugg aauauuagau 20 <210> 1725 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> ombination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1725 auguccugga auauuagaug 20 <210> 1726 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1726 uguccuggaa uauuagaugc 20 <210> 1727 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1727 guccuggaau auuagaugcc 20 <210> 1728 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1728 uccuggaaua uuagaugccu 20 <210> 1729 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1729 ccuggaauau uagaugccuu 20 <210> 1730 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1730 cuggaauauu agaugccuuu 20 <210> 1731 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1731 caugguguuu cagaacugag 20 <210> 1732 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1732 augguguuuc agaacugaga 20 <210> 1733 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1733 ugguguuuca gaacugagac 20 <210> 1734 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1734 gguguuucag aacugagacc 20 <210> 1735 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1735 gaggagaaga aaagugauuc 20 <210> 1736 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1736 agaagaaaag ugauucagug 20 <210> 1737 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1737 gaagaaaagu gauucaguga 20 <210> 1738 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1738 gaaaagugau ucagugauuu 20 <210> 1739 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1739 aaagugauuc agugauuuca 20 <210> 1740 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1740 acuacugaaa accuuuaaag 20 <210> 1741 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1741 uacugaaaac cuuuaaaggg 20 <210> 1742 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1742 uguauaacuc uaagaucuga 20 <210> 1743 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1743 uauaacucua agaucugaug 20 <210> 1744 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1744 auaacucuaa gaucugauga 20 <210> 1745 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1745 uaacucuaag aucugaugaa 20 <210> 1746 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1746 aacucuaaga ucugaugaag 20 <210> 1747 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1747 acucuaagau cugaugaagu 20 <210> 1748 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1748 gauuggcccg gaaggguuca 20 <210> 1749 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1749 ccuuugggcu cggggccaaa 20 <210> 1750 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1750 uugggcucgg ggccaaaggc 20 <210> 1751 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1751 cgcaccuucc cccagcggcc 20 <210> 1752 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1752 ccgccgccac cucgcggaga 20 <210> 1753 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1753 uccgcgcugg cgcgcuuugu 20 <210> 1754 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1754 ccgcgcuggc gcgcuuuguc 20 <210> 1755 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1755 cgcgcuggcg cgcuuugucc 20 <210> 1756 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1756 cgcgcuuugu ccuccucgcg 20 <210> 1757 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1757 gcgcuuuguc cuccucgcgc 20 <210> 1758 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1758 cgcuuugucc uccucgcgca 20 <210> 1759 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1759 gcuuuguccu ccucgcgcaa 20 <210> 1760 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1760 cuuuguccuc cucgcgcaau 20 <210> 1761 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1761 uuuguccucc ucgcgcaauc 20 <210> 1762 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1762 uguccuccuc gcgcaauccc 20 <210> 1763 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1763 guccuccucg cgcaaucccg 20 <210> 1764 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1764 uccuccucgc gcaaucccgg 20 <210> 1765 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1765 ccuccucgcg caaucccggc 20 <210> 1766 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1766 cucgcgcaau cccggcccgg 20 <210> 1767 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1767 gcgcaauccc ggcccgggug 20 <210> 1768 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1768 cgcaaucccg gcccgggugg 20 <210> 1769 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1769 gcaaucccgg cccggguggc 20 <210> 1770 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1770 ggcccgggug gcucgggguu 20 <210> 1771 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1771 gcccgggugg cucgggguug 20 <210> 1772 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1772 cccggguggc ucgggguugc 20 <210> 1773 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1773 ucgggguugc cgcgcugggc 20 <210> 1774 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1774 gguugccgcg cugggccuga 20 <210> 1775 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1775 gccgcgcugg gccugaccgc 20 <210> 1776 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1776 gcgcugggcc ugaccgcggu 20 <210> 1777 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1777 ugggccugac cgcgguggcg 20 <210> 1778 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1778 gggccugacc gcgguggcgc 20 <210> 1779 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1779 gagggaaaca ugguuacugc 20 <210> 1780 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1780 ggaaacaugg uuacugcucg 20 <210> 1781 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1781 gaaacauggu uacugcucgc 20 <210> 1782 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1782 aaacaugguu acugcucgcc 20 <210> 1783 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1783 aacaugguua cugcucgcca 20 <210> 1784 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1784 guuacugcuc gccaggaacc 20 <210> 1785 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1785 guuacugcuc gccaggaacc 20 <210> 1786 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1786 uucccugacc ugcgauggug 20 <210> 1787 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1787 accugcgaug gugacacccu 20 <210> 1788 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1788 gugcagccua cacaaaggac 20 <210> 1789 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1789 ugcagccuac acaaaggacc 20 <210> 1790 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1790 cagccuacac aaaggaccua 20 <210> 1791 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1791 agccuacaca aaggaccuac 20 <210> 1792 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1792 gccuacacaa aggaccuacu 20 <210> 1793 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1793 ccuacacaaa ggaccuacua 20 <210> 1794 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1794 cuacacaaag gaccuacuac 20 <210> 1795 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1795 cacaaaggac cuacuacugc 20 <210> 1796 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1796 aggaccuacu acugccuauc 20 <210> 1797 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1797 ggaccuacua cugccuauca 20 <210> 1798 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1798 accuacuacu gccuaucaaa 20 <210> 1799 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1799 uacuacugcc uaucaaaacg 20 <210> 1800 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1800 cuacugccua ucaaaacgcc 20 <210> 1801 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1801 gccuaucaaa acgcccacca 20 <210> 1802 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1802 accacaaaug cagugcacaa 20 <210> 1803 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1803 cacaaaugca gugcacaagu 20 <210> 1804 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1804 caaaugcagu gcacaagugc 20 <210> 1805 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1805 augcagugca caagugcaga 20 <210> 1806 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1806 agugcacaag ugcagagugc 20 <210> 1807 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1807 acaagugcag agugcacggc 20 <210> 1808 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1808 caagugcaga gugcacggcc 20 <210> 1809 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1809 ugcagagugc acggccugga 20 <210> 1810 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1810 agagugcacg gccuggagau 20 <210> 1811 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1811 gagugcacgg ccuggagaua 20 <210> 1812 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1812 uggagauaga gggcagggac 20 <210> 1813 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1813 uccugaaguc acagcccuac 20 <210> 1814 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1814 cugaagucac agcccuaccg 20 <210> 1815 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1815 gaagucacag cccuaccgcc 20 <210> 1816 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1816 ccucacaugc gaccgagacg 20 <210> 1817 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1817 cucacaugcg accgagacgu 20 <210> 1818 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1818 ucacaugcga ccgagacguc 20 <210> 1819 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1819 cacaugcgac cgagacgucc 20 <210> 1820 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1820 acaugcgacc gagacguccu 20 <210> 1821 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1821 ugcgaccgag acguccucau 20 <210> 1822 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1822 gcgaccgaga cguccucauc 20 <210> 1823 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1823 ccgagacguc cucaucaaau 20 <210> 1824 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1824 cgagacgucc ucaucaaaua 20 <210> 1825 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1825 agacguccuc aucaaauagc 20 <210> 1826 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1826 uccucaucaa auagcagacu 20 <210> 1827 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1827 cucaucaaau agcagacuug 20 <210> 1828 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1828 cagacaccag cccauucuug 20 <210> 1829 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1829 agacaccagc ccauucuuga 20 <210> 1830 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1830 gacaccagcc cauucuugau 20 <210> 1831 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1831 cagcccauuc uugauccuuu 20 <210> 1832 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1832 ccauucuuga uccuuucuga 20 <210> 1833 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1833 gcagaggauu cuugggauga 20 <210> 1834 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1834 auucuuggga ugagcuucuu 20 <210> 1835 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1835 cuugggauga gcuucuuauu 20 <210> 1836 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1836 gggaugagcu ucuuauuggu 20 <210> 1837 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1837 ggaugagcuu cuuauuggug 20 <210> 1838 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1838 guggaacuga aaagggugau 20 <210> 1839 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1839 uggaacugaa aagggugaug 20 <210> 1840 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1840 gaacugaaaa gggugauggc 20 <210> 1841 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1841 cugaaaaggg ugauggcuug 20 <210> 1842 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1842 ugaaaagggu gauggcuugu 20 <210> 1843 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1843 gaaaagggug auggcuuguu 20 <210> 1844 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1844 aaaaggguga uggcuuguuc 20 <210> 1845 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1845 guggacccag acaccggugu 20 <210> 1846 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1846 uggacccaga caccgguguc 20 <210> 1847 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1847 ggacccagac accgguguca 20 <210> 1848 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1848 acccagacac cggugucaug 20 <210> 1849 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1849 ccagacaccg gugucaugag 20 <210> 1850 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1850 caccgguguc augagcagga 20 <210> 1851 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1851 gucaugagca ggaaggaacc 20 <210> 1852 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1852 augagcagga aggaaccgcu 20 <210> 1853 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1853 aggaaggaac cgcuggaaac 20 <210> 1854 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1854 ggaaggaacc gcuggaaaca 20 <210> 1855 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1855 gaaggaaccg cuggaaacac 20 <210> 1856 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1856 cugggccagu aaugggaacc 20 <210> 1857 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1857 gggccaguaa ugggaaccgu 20 <210> 1858 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1858 ggccaguaau gggaaccgua 20 <210> 1859 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1859 gccaguaaug ggaaccguau 20 <210> 1860 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1860 ccaguaaugg gaaccguaug 20 <210> 1861 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1861 caguaauggg aaccguaugu 20 <210> 1862 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1862 aguaauggga accguauguc 20 <210> 1863 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1863 ugggaaccgu auguccugga 20 <210> 1864 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1864 ggaaccguau guccuggaau 20 <210> 1865 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1865 gaauauuaga ugccuuuuaa 20 <210> 1866 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1866 gaugccuuuu aaaaauguuc 20 <210> 1867 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1867 guuucagaac ugagaccucu 20 <210> 1868 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1868 ucagaacuga gaccucuaca 20 <210> 1869 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1869 acugagaccu cuacauuuuc 20 <210> 1870 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1870 cugagaccuc uacauuuucu 20 <210> 1871 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1871 ugagaccucu acauuuucuu 20 <210> 1872 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1872 ugauuuucac auuuuucguc 20 <210> 1873 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1873 gauuuucaca uuuuucgucu 20 <210> 1874 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1874 auuuucacau uuuucgucuu 20 <210> 1875 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1875 uuucacauuu uucgucuuuu 20 <210> 1876 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1876 uucacauuuu ucgucuuuug 20 <210> 1877 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1877 ucacauuuuu cgucuuuugg 20 <210> 1878 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1878 acauuuuucg ucuuuuggac 20 <210> 1879 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1879 uuuucgucuu uuggacuucu 20 <210> 1880 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1880 uuucgucuuu uggacuucug 20 <210> 1881 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1881 uucgucuuuu ggacuucugg 20 <210> 1882 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1882 ucgucuuuug gacuucuggu 20 <210> 1883 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1883 cuuuuggacu ucuggugucu 20 <210> 1884 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1884 uuggacuucu ggugucucaa 20 <210> 1885 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1885 ggacuucugg ugucucaaug 20 <210> 1886 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1886 gacuucuggu gucucaaugc 20 <210> 1887 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1887 uucugguguc ucaaugcuuc 20 <210> 1888 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1888 gcuucaaugu cccagugcaa 20 <210> 1889 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1889 augucccagu gcaaaaagua 20 <210> 1890 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1890 ugucccagug caaaaaguaa 20 <210> 1891 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1891 gucccagugc aaaaaguaaa 20 <210> 1892 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1892 ucccagugca aaaaguaaag 20 <210> 1893 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1893 agugcaaaaa guaaagaaau 20 <210> 1894 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1894 aagaaauaua gucucaauaa 20 <210> 1895 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1895 aaauauaguc ucaauaacuu 20 <210> 1896 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1896 auauagucuc aauaacuuag 20 <210> 1897 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1897 uauagucuca auaacuuagu 20 <210> 1898 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1898 auagucucaa uaacuuagua 20 <210> 1899 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1899 uagucucaau aacuuaguag 20 <210> 1900 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1900 agucucaaua acuuaguagg 20 <210> 1901 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1901 ucaauaacuu aguaggacuu 20 <210> 1902 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1902 caauaacuua guaggacuuc 20 <210> 1903 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1903 auaacuuagu aggacuucag 20 <210> 1904 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1904 aacuuaguag gacuucagua 20 <210> 1905 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1905 acuuaguagg acuucaguaa 20 <210> 1906 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1906 uuaguaggac uucaguaagu 20 <210> 1907 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1907 uaguaggacu ucaguaaguc 20 <210> 1908 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1908 aguaggacuu caguaaguca 20 <210> 1909 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1909 uaggacuuca guaagucacu 20 <210> 1910 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1910 uaaaugacaa gacaggauuc 20 <210> 1911 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1911 ggauucugaa aacuccccgu 20 <210> 1912 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1912 gauucugaaa acuccccguu 20 <210> 1913 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1913 uucugaaaac uccccguuua 20 <210> 1914 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1914 ucugaaaacu ccccguuuaa 20 <210> 1915 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1915 cugaaaacuc cccguuuaac 20 <210> 1916 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1916 ugaaaacucc ccguuuaacu 20 <210> 1917 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1917 aaaacucccc guuuaacuga 20 <210> 1918 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1918 acuccccguu uaacugauua 20 <210> 1919 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1919 cuccccguuu aacugauuau 20 <210> 1920 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1920 uccccguuua acugauuaug 20 <210> 1921 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1921 ccccguuuaa cugauuaugg 20 <210> 1922 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1922 uucuccugcu ucuccguuua 20 <210> 1923 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1923 ucuccugcuu cuccguuuau 20 <210> 1924 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1924 cuccugcuuc uccguuuauc 20 <210> 1925 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1925 ccugcuucuc cguuuaucua 20 <210> 1926 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1926 gcuucuccgu uuaucuacca 20 <210> 1927 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1927 cuucuccguu uaucuaccaa 20 <210> 1928 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1928 uucuccguuu aucuaccaag 20 <210> 1929 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1929 ucuccguuua ucuaccaaga 20 <210> 1930 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1930 cuccguuuau cuaccaagag 20 <210> 1931 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1931 uccguuuauc uaccaagagc 20 <210> 1932 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1932 cguuuaucua ccaagagcgc 20 <210> 1933 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1933 uuaucuacca agagcgcaga 20 <210> 1934 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1934 aucuaccaag agcgcagacu 20 <210> 1935 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1935 uaccaagagc gcagacuugc 20 <210> 1936 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1936 accaagagcg cagacuugca 20 <210> 1937 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1937 caagagcgca gacuugcauc 20 <210> 1938 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1938 aagagcgcag acuugcaucc 20 <210> 1939 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1939 gagcgcagac uugcauccug 20 <210> 1940 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1940 gcgcagacuu gcauccuguc 20 <210> 1941 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1941 cgcagacuug cauccuguca 20 <210> 1942 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1942 cagacuugca uccugucacu 20 <210> 1943 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1943 cuugcauccu gucacuacca 20 <210> 1944 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1944 cauccuguca cuaccacucg 20 <210> 1945 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1945 uccugucacu accacucguu 20 <210> 1946 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1946 ccugucacua ccacucguua 20 <210> 1947 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1947 cugucacuac cacucguuag 20 <210> 1948 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1948 ugucacuacc acucguuaga 20 <210> 1949 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1949 acuaccacuc guuagagaaa 20 <210> 1950 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1950 aagagugggu gggcuggaag 20 <210> 1951 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1951 uccuagaaug uguuauugcc 20 <210> 1952 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1952 ccuagaaugu guuauugccc 20 <210> 1953 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1953 aauguguuau ugccccuguu 20 <210> 1954 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1954 guguuauugc cccuguucau 20 <210> 1955 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1955 uuauugcccc uguucaugag 20 <210> 1956 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1956 auugccccug uucaugaggu 20 <210> 1957 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1957 aaugaaaauu aaauugcacc 20 <210> 1958 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1958 augaaaauua aauugcaccc 20 <210> 1959 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1959 aaauuaaauu gcaccccaaa 20 <210> 1960 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1960 auuaaauugc accccaaaua 20 <210> 1961 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1961 uuaaauugca ccccaaauau 20 <210> 1962 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1962 aauugcaccc caaauauggc 20 <210> 1963 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1963 auugcacccc aaauauggcu 20 <210> 1964 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1964 auauggcugg aaugccacuu 20 <210> 1965 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1965 uggaaugcca cuucccuuuu 20 <210> 1966 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1966 uucccuuuuc uucucaagcc 20 <210> 1967 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1967 ucuucucaag ccccgggcua 20 <210> 1968 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1968 ucucaagccc cgggcuagcu 20 <210> 1969 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1969 gcuuuugaaa uggcauaaag 20 <210> 1970 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1970 uuugaaaugg cauaaagacu 20 <210> 1971 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1971 aauggcauaa agacugaggu 20 <210> 1972 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1972 uggcauaaag acugagguga 20 <210> 1973 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1973 gcauaaagac ugaggugacc 20 <210> 1974 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1974 gaagcacugc agauauuaau 20 <210> 1975 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1975 cuaaaggugc ucaggaggau 20 <210> 1976 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1976 aggugcucag gaggaugguu 20 <210> 1977 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1977 gugcucagga ggaugguugu 20 <210> 1978 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1978 gaggaugguu guguagucau 20 <210> 1979 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1979 aggaugguug uguagucaug 20 <210> 1980 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1980 ggaugguugu guagucaugg 20 <210> 1981 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1981 uuguguaguc auggaggacc 20 <210> 1982 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1982 ucauggagga ccccuggauc 20 <210> 1983 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1983 auuccccuca gcuaaugacg 20 <210> 1984 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1984 uuccccucag cuaaugacgg 20 <210> 1985 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1985 uccccucagc uaaugacgga 20 <210> 1986 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1986 ucagcuaaug acggagugcu 20 <210> 1987 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1987 gaaaaaguuc ugaauucugu 20 <210> 1988 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1988 aguucugaau ucuguggagg 20 <210> 1989 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1989 agugauuuca gauagacuac 20 <210> 1990 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1990 auuucagaua gacuacugaa 20 <210> 1991 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1991 cagauagacu acugaaaacc 20 <210> 1992 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1992 uagacuacug aaaaccuuua 20 <210> 1993 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1993 agacuacuga aaaccuuuaa 20 <210> 1994 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1994 aaggaaagca uaugucaguu 20 <210> 1995 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1995 aggaaagcau augucaguug 20 <210> 1996 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1996 ggaaagcaua ugucaguugu 20 <210> 1997 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1997 aaagcauaug ucaguuguuu 20 <210> 1998 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1998 aagcauaugu caguuguuua 20 <210> 1999 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 1999 agcauauguc aguuguuuaa 20 <210> 2000 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2000 uaaaacccaa uaucuauuuu 20 <210> 2001 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2001 aacccaauau cuauuuuuua 20 <210> 2002 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2002 uuaacugauu guauaacucu 20 <210> 2003 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2003 uaacugauug uauaacucua 20 <210> 2004 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2004 acugauugua uaacucuaag 20 <210> 2005 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2005 cugauuguau aacucuaaga 20 <210> 2006 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2006 gauuguauaa cucuaagauc 20 <210> 2007 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2007 gccauuuugu ccuuugauua 20 <210> 2008 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2008 uguccuuuga uuauauuggg 20 <210> 2009 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2009 aggcccaaua uuguaauuuc 20 <210> 2010 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2010 cagaacgaaa guuauaugga 20 <210> 2011 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2011 uuccagaugc auuuuaacca 20 <210> 2012 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2012 ugcauuuuaa ccacagugga 20 <210> 2013 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2013 ccaguggaua accagcuucc 20 <210> 2014 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2014 gcuggaaaca cugaagaguu 20 <210> 2015 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2015 gaaacacuga agaguuaucg 20 <210> 2016 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2016 aacacugaag aguuaucgcc 20 <210> 2017 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2017 cccguuuaac ugauuaugga 20 <210> 2018 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2018 aaaugacaac acuugaagca 20 <210> 2019 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2019 cacuugaagc augguguuuc 20 <210> 2020 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2020 gauuauggaa uaguucuuuc 20 <210> 2021 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2021 auuauggaau aguucuuucu 20 <210> 2022 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2022 uggugucuca augcuucaau 20 <210> 2023 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2023 gacaagacag gauucugaaa 20 <210> 2024 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2024 cauaugucag uuguuuaaaa 20 <210> 2025 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2025 aguuguuuaa aacccaauau 20 <210> 2026 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2026 uuguuuaaaa cccaauaucu 20 <210> 2027 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2027 gaugaaguau auuuuuuauu 20 <210> 2028 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2028 uuuuauugcc auuuuguccu 20 <210> 2029 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2029 auugccauuu uguccuuuga 20 <210> 2030 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2030 auauugggaa guugacuaaa 20 <210> 2031 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2031 ggaaguugac uaaacuugaa 20 <210> 2032 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2032 acugugaaua aauggaagcu 20 <210> 2033 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2033 cagauugcuu acucagacac 20 <210> 2034 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2034 cugaagaguu aucgccagug 20 <210> 2035 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2035 acccuucaga acgaaaguua 20 <210> 2036 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2036 gugacccuuc agaacgaaag 20 <210> 2037 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2037 ucagaacgaa aguuauaugg 20 <210> 2038 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2038 uucuuauugg ugacguggaa 20 <210> 2039 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2039 aguuauaugg aaaaucacca 20 <210> 2040 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2040 cccuucagaa cgaaaguuau 20 <210> 2041 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2041 ccuucagaac gaaaguuaua 20 <210> 2042 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2042 cuucagaacg aaaguuauau 20 <210> 2043 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2043 caacuucagg cccaauauug 20 <210> 2044 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2044 ggaaacacug aagaguuauc 20 <210> 2045 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2045 acuucaggcc caauauugua 20 <210> 2046 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2046 aaguuaaagc aaccaacuuc 20 <210> 2047 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2047 cuucaggccc aauauuguaa 20 <210> 2048 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2048 gaccagauug cuuacucaga 20 <210> 2049 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2049 acugauuaug gaauaguucu 20 <210> 2050 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2050 auauggaaaa ucaccacucu 20 <210> 2051 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2051 caaugcuuca augucccagu 20 <210> 2052 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2052 ugcuucaaug ucccagugca 20 <210> 2053 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2053 aaugacaaga caggauucug 20 <210> 2054 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2054 cuaagaucug augaaguaua 20 <210> 2055 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2055 cuggugucuc aaugcuucaa 20 <210> 2056 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2056 ugucucaaug cuucaauguc 20 <210> 2057 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2057 uuuuccauag aucuggaucu 20 <210> 2058 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2058 ugugacccuu cagaacgaaa 20 <210> 2059 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2059 cagugugacc cuucagaacg 20 <210> 2060 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2060 caccccaaau auggcuggaa 20 <210> 2061 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2061 cucaaugcuu caauguccca 20 <210> 2062 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2062 acaggauucu gaaaacuccc 20 <210> 2063 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2063 ggauccuugc cauuccccuc 20 <210> 2064 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2064 cugcagauau uaauuuucca 20 <210> 2065 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2065 aagaucugau gaaguauauu 20 <210> 2066 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2066 aauagcagac uuguuccgac 20 <210> 2067 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2067 gacaacacuu gaagcauggu 20 <210> 2068 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2068 ucagacagca uuggauuucc 20 <210> 2069 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2069 uggaaaauca ccacucuuug 20 <210> 2070 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2070 agacagcauu ggauuuccua 20 <210> 2071 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 2071 cugauuaugg aauaguucuu 20 <210> 2072 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2072 uuccauauag ugcuugcucg u 21 <210> 2073 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2073 ucauuugccg agaacuucug u 21 <210> 2074 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2074 uuccaaauuc agcuugcucg u 21 <210> 2075 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2075 ucauuagcgc ugaacuucug u 21 <210> 2076 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2076 aaucagagca gugcguccuu cuu 23 <210> 2077 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2077 acaaucagag cagugcgucc uuu 23 <210> 2078 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2078 accaaucaga gcagugcguc cuu 23 <210> 2079 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2079 aggccaauca gagcagugcg uuu 23 <210> 2080 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2080 auuccgggcc aaucagagca guu 23 <210> 2081 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2081 acuuccgggc caaucagagc auu 23 <210> 2082 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2082 accuuccggg ccaaucagag cuu 23 <210> 2083 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2083 aaggugcggc cuuuggcccc guu 23 <210> 2084 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2084 aaaggugcgg ccuuuggccc cuu 23 <210> 2085 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2085 agggaaggug cggccuuugg cuu 23 <210> 2086 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2086 aggggaaggu gcggccuuug guu 23 <210> 2087 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2087 uggcuucucc gcgagguggc guu 23 <210> 2088 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2088 auggcuucuc cgcgaggugg cuu 23 <210> 2089 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2089 acuggcuucu ccgcgaggug guu 23 <210> 2090 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2090 uggcuggcuu cuccgcgagg uuu 23 <210> 2091 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2091 uguuucccuc cugguugauc auu 23 <210> 2092 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2092 aauguuuccc uccugguuga uuu 23 <210> 2093 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2093 acauguuucc cuccugguug auu 23 <210> 2094 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2094 accauguuuc ccuccugguu guu 23 <210> 2095 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2095 aaccauguuu cccuccuggu uuu 23 <210> 2096 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2096 uaaccauguu ucccuccugg uuu 23 <210> 2097 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2097 aggcgagguu ccuggcgagc auu 23 <210> 2098 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2098 acaggcgagg uuccuggcga guu 23 <210> 2099 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2099 aucaggacca ggcgagguuc cuu 23 <210> 2100 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2100 aaaucaggac caggcgaggu uuu 23 <210> 2101 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2101 aaaaucagga ccaggcgagg uuu 23 <210> 2102 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2102 agaaaucagg accaggcgag guu 23 <210> 2103 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2103 aggaaaucag gaccaggcga guu 23 <210> 2104 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2104 aucagggaaa ucaggaccag guu 23 <210> 2105 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2105 auguaggcug cacugagagu cuu 23 <210> 2106 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2106 uuguguaggc ugcacugaga guu 23 <210> 2107 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2107 uuuguguagg cugcacugag auu 23 <210> 2108 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2108 auuuguguag gcugcacuga guu 23 <210> 2109 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2109 acuuugugua ggcugcacug auu 23 <210> 2110 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2110 uugugguggg cguuuugaua guu 23 <210> 2111 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2111 uuuguggugg gcguuuugau auu 23 <210> 2112 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2112 auuuguggug ggcguuuuga uuu 23 <210> 2113 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2113 aauuuguggu gggcguuuug auu 23 <210> 2114 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2114 augcauuugu ggugggcguu uuu 23 <210> 2115 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2115 acugcauuug uggugggcgu uuu 23 <210> 2116 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2116 aggaagcugg uuauccacug guu 23 <210> 2117 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2117 aaggaagcug guuauccacu guu 23 <210> 2118 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2118 uucaggaagc ugguuaucca cuu 23 <210> 2119 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2119 aacuucagga agcugguuau cuu 23 <210> 2120 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2120 agaacaaguc ugcuauuuga uuu 23 <210> 2121 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2121 ucggaacaag ucugcuauuu guu 23 <210> 2122 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2122 aucggaacaa gucugcuauu uuu 23 <210> 2123 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2123 acgucaccaa uaagaagcuc auu 23 <210> 2124 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2124 acacgucacc aauaagaagc uuu 23 <210> 2125 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2125 uccacgucac caauaagaag cuu 23 <210> 2126 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2126 auuccacguc accaauaaga auu 23 <210> 2127 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2127 uuuucaguuc cacgucacca auu 23 <210> 2128 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2128 auuuucaguu ccacgucacc auu 23 <210> 2129 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2129 acuuuucagu uccacgucac cuu 23 <210> 2130 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2130 accuuuucag uuccacguca cuu 23 <210> 2131 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2131 uaaaaugcau cuggaacaag cuu 23 <210> 2132 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2132 ugguuaaaau gcaucuggaa cuu 23 <210> 2133 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2133 augguuaaaa ugcaucugga auu 23 <210> 2134 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2134 auccacugug guuaaaaugc auu 23 <210> 2135 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2135 aguccacugu gguuaaaaug cuu 23 <210> 2136 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2136 uuccuuccug cucaugacac cuu 23 <210> 2137 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2137 auucaguguu uccagcgguu cuu 23 <210> 2138 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2138 uaacucuuca guguuuccag cuu 23 <210> 2139 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2139 agauaacucu ucaguguuuc cuu 23 <210> 2140 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2140 acgauaacuc uucaguguuu cuu 23 <210> 2141 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2141 agcgauaacu cuucaguguu uuu 23 <210> 2142 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2142 uggcgauaac ucuucagugu uuu 23 <210> 2143 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2143 auggcgauaa cucuucagug uuu 23 <210> 2144 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2144 acuggcgaua acucuucagu guu 23 <210> 2145 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2145 aacuggcgau aacucuucag uuu 23 <210> 2146 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2146 acacuggcga uaacucuuca guu 23 <210> 2147 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2147 aacacuggcg auaacucuuc auu 23 <210> 2148 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2148 ucacacuggc gauaacucuu cuu 23 <210> 2149 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2149 aggucacacu ggcgauaacu cuu 23 <210> 2150 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2150 agggucacac uggcgauaac uuu 23 <210> 2151 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2151 aagggucaca cuggcgauaa cuu 23 <210> 2152 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2152 aaagggucac acuggcgaua auu 23 <210> 2153 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2153 uucugaaggg ucacacuggc guu 23 <210> 2154 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2154 auucugaagg gucacacugg cuu 23 <210> 2155 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2155 ucguucugaa gggucacacu guu 23 <210> 2156 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2156 uucguucuga agggucacac uuu 23 <210> 2157 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2157 uuucguucug aagggucaca cuu 23 <210> 2158 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2158 auuucguucu gaagggucac auu 23 <210> 2159 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2159 acuuucguuc ugaaggguca cuu 23 <210> 2160 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2160 aacuuucguu cugaaggguc auu 23 <210> 2161 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2161 uaacuuucgu ucugaagggu cuu 23 <210> 2162 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2162 auaacuuucg uucugaaggg uuu 23 <210> 2163 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2163 uauaacuuuc guucugaagg guu 23 <210> 2164 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2164 auauaacuuu cguucugaag guu 23 <210> 2165 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2165 aauauaacuu ucguucugaa guu 23 <210> 2166 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2166 acauauaacu uucguucuga auu 23 <210> 2167 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2167 uccauauaac uuucguucug auu 23 <210> 2168 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2168 uuccauauaa cuuucguucu guu 23 <210> 2169 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2169 auggugauuu uccauauaac uuu 23 <210> 2170 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2170 aaguggugau uuuccauaua auu 23 <210> 2171 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2171 agucggaaca agucugcuau uuu 23 <210> 2172 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2172 aggucggaac aagucugcua uuu 23 <210> 2173 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2173 ugggucggaa caagucugcu auu 23 <210> 2174 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2174 uugggucgga acaagucugc uuu 23 <210> 2175 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2175 auugggucgg aacaagucug cuu 23 <210> 2176 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2176 acuugggucg gaacaagucu guu 23 <210> 2177 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2177 uccuuggguc ggaacaaguc uuu 23 <210> 2178 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2178 auccuugggu cggaacaagu cuu 23 <210> 2179 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2179 aguccuuggg ucggaacaag uuu 23 <210> 2180 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2180 ugguccuugg gucggaacaa guu 23 <210> 2181 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2181 aaucuggucc uugggucgga auu 23 <210> 2182 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2182 ugaguaagca aucugguccu uuu 23 <210> 2183 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2183 aucugaguaa gcaaucuggu cuu 23 <210> 2184 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2184 augucugagu aagcaaucug guu 23 <210> 2185 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2185 agugucugag uaagcaaucu guu 23 <210> 2186 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2186 uggugucuga guaagcaauc uuu 23 <210> 2187 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2187 auggugucug aguaagcaau cuu 23 <210> 2188 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2188 acuggugucu gaguaagcaa uuu 23 <210> 2189 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2189 ugggcuggug ucugaguaag cuu 23 <210> 2190 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2190 aaugggcugg ugucugagua auu 23 <210> 2191 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2191 auagccugga guugagaucc guu 23 <210> 2192 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2192 ucuagccugg aguugagauc cuu 23 <210> 2193 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2193 aucuagccug gaguugagau cuu 23 <210> 2194 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2194 ucucuagccu ggaguugaga uuu 23 <210> 2195 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2195 uuucuucucu agccuggagu uuu 23 <210> 2196 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2196 ugguugcuuu aacuuucuuc uuu 23 <210> 2197 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2197 uugguugcuu uaacuuucuu cuu 23 <210> 2198 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2198 auugguugcu uuaacuuucu uuu 23 <210> 2199 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2199 aguugguugc uuuaacuuuc uuu 23 <210> 2200 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2200 aaguugguug cuuuaacuuu cuu 23 <210> 2201 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2201 aaaguugguu gcuuuaacuu uuu 23 <210> 2202 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2202 ugaaguuggu ugcuuuaacu uuu 23 <210> 2203 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2203 augaaguugg uugcuuuaac uuu 23 <210> 2204 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2204 acugaaguug guugcuuuaa cuu 23 <210> 2205 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2205 agsgccugaa guugguugcu uuuu 24 <210> 2206 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2206 uusgggccug aaguugguug cuuu 24 <210> 2207 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2207 uauugggccu gaaguugguu guu 23 <210> 2208 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2208 auauugggcc ugaaguuggu uuu 23 <210> 2209 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2209 aaauauuggg ccugaaguug guu 23 <210> 2210 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2210 acaauauugg gccugaaguu guu 23 <210> 2211 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2211 uuacaauauu gggccugaag uuu 23 <210> 2212 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2212 auuacaauau ugggccugaa guu 23 <210> 2213 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2213 aauuacaaua uugggccuga auu 23 <210> 2214 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2214 aaauuacaau auugggccug auu 23 <210> 2215 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2215 ugaaauuaca auauugggcc uuu 23 <210> 2216 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2216 augaaauuac aauauugggc cuu 23 <210> 2217 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2217 aucaccaaua agaagcucau cuu 23 <210> 2218 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2218 agucaccaau aagaagcuca uuu 23 <210> 2219 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2219 aagaguggug auuuuccaua uuu 23 <210> 2220 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2220 aaagaguggu gauuuuccau auu 23 <210> 2221 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2221 aaaagagugg ugauuuucca uuu 23 <210> 2222 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2222 acaaagagug gugauuuucc auu 23 <210> 2223 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2223 aauggucccu ggguuuucca guu 23 <210> 2224 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2224 uugauggucc cuggguuuuc cuu 23 <210> 2225 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2225 uuugaugguc ccuggguuuu cuu 23 <210> 2226 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2226 accacuuuga uggucccugg guu 23 <210> 2227 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2227 ucccacuuug auggucccug guu 23 <210> 2228 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2228 aucucccacu uugauggucc cuu 23 <210> 2229 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2229 agcagguaca cagggucucc cuu 23 <210> 2230 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2230 aauuacuggc ccagcaggua cuu 23 <210> 2231 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2231 auucccauua cuggcccagc auu 23 <210> 2232 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2232 uugucauuuu ugagaacauu uuu 23 <210> 2233 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2233 auugucauuu uugagaacau uuu 23 <210> 2234 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2234 ugcuucaagu guugucauuu uuu 23 <210> 2235 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2235 ausgcuucaa guguugucau uuuu 24 <210> 2236 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2236 aaugcuucaa guguugucau uuu 23 <210> 2237 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2237 accaugcuuc aaguguuguc auu 23 <210> 2238 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2238 aaccaugcuu caaguguugu cuu 23 <210> 2239 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2239 acaccaugcu ucaaguguug uuu 23 <210> 2240 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2240 ugaaacacca ugcuucaagu guu 23 <210> 2241 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2241 ucugaaacac caugcuucaa guu 23 <210> 2242 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2242 auugaagcau ugagacacca guu 23 <210> 2243 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2243 aauugaagca uugagacacc auu 23 <210> 2244 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2244 acauugaagc auugagacac cuu 23 <210> 2245 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2245 aacauugaag cauugagaca cuu 23 <210> 2246 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2246 agacauugaa gcauugagac auu 23 <210> 2247 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2247 ugggacauug aagcauugag auu 23 <210> 2248 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2248 augggacauu gaagcauuga guu 23 <210> 2249 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2249 aacugggaca uugaagcauu guu 23 <210> 2250 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2250 ugcacuggga cauugaagca uuu 23 <210> 2251 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2251 uugcacuggg acauugaagc auu 23 <210> 2252 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2252 ucagaauccu gucuugucau uuu 23 <210> 2253 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2253 uucagaaucc ugucuuguca uuu 23 <210> 2254 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2254 uuuucagaau ccugucuugu cuu 23 <210> 2255 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2255 aaguuuucag aauccugucu uuu 23 <210> 2256 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2256 agggaguuuu cagaauccug uuu 23 <210> 2257 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2257 uuccauaauc aguuaaacgg guu 23 <210> 2258 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2258 acuauuccau aaucaguuaa auu 23 <210> 2259 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2259 aacuauucca uaaucaguua auu 23 <210> 2260 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2260 agaacuauuc cauaaucagu uuu 23 <210> 2261 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2261 aagaacuauu ccauaaucag uuu 23 <210> 2262 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2262 aaagaacuau uccauaauca guu 23 <210> 2263 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2263 agaaagaacu auuccauaau cuu 23 <210> 2264 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2264 aagaaagaac uauuccauaa uuu 23 <210> 2265 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2265 agugguagug acaggaugca auu 23 <210> 2266 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2266 auuccagcca uauuuggggu guu 23 <210> 2267 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2267 acauuccagc cauauuuggg guu 23 <210> 2268 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2268 aaagcuagcc cggggcuuga guu 23 <210> 2269 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2269 aaaagcuagc ccggggcuug auu 23 <210> 2270 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2270 ucaaaagcua gcccggggcu uuu 23 <210> 2271 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2271 uucaaaagcu agcccggggc uuu 23 <210> 2272 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2272 uuucaaaagc uagcccgggg cuu 23 <210> 2273 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2273 aauuucaaaa gcuagcccgg guu 23 <210> 2274 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2274 augccauuuc aaaagcuagc cuu 23 <210> 2275 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2275 aaaggucacc ucagucuuua uuu 23 <210> 2276 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2276 ausggaaaau uaauaucugc aguu 24 <210> 2277 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2277 aaucuaugga aaauuaauau cuu 23 <210> 2278 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2278 agaucuaugg aaaauuaaua uuu 23 <210> 2279 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2279 auccagaucu auggaaaauu auu 23 <210> 2280 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2280 aauccagauc uauggaaaau uuu 23 <210> 2281 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2281 agauccagau cuauggaaaa uuu 23 <210> 2282 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2282 acagauccag aucuauggaa auu 23 <210> 2283 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2283 uccaaugcug ucugagaagc auu 23 <210> 2284 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2284 auccaaugcu gucugagaag cuu 23 <210> 2285 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2285 aggaaaucca augcugucug auu 23 <210> 2286 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2286 uaggaaaucc aaugcugucu guu 23 <210> 2287 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2287 uuaggaaauc caaugcuguc uuu 23 <210> 2288 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2288 acuccugagc accuuuagga auu 23 <210> 2289 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2289 uggcaaggau ccaggggucc uuu 23 <210> 2290 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2290 aggaauggca aggauccagg guu 23 <210> 2291 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2291 aggggaaugg caaggaucca guu 23 <210> 2292 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2292 ugaggggaau ggcaaggauc cuu 23 <210> 2293 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2293 augaggggaa uggcaaggau cuu 23 <210> 2294 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2294 uagcugaggg gaauggcaag guu 23 <210> 2295 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2295 uuagcugagg ggaauggcaa guu 23 <210> 2296 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2296 ucauuagcug aggggaaugg cuu 23 <210> 2297 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2297 agucauuagc ugaggggaau guu 23 <210> 2298 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2298 acuggagaag gagcacuccg uuu 23 <210> 2299 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2299 uuucccccuu uaaagguuuu cuu 23 <210> 2300 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2300 auuuuaaaca acugacauau guu 23 <210> 2301 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2301 uauuggguuu uaaacaacug auu 23 <210> 2302 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2302 aauauugggu uuuaaacaac uuu 23 <210> 2303 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2303 aaaucagagc agugcguccu uuu 23 <210> 2304 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2304 aaaaagcuag cccggggcuu guu 23 <210> 2305 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2305 auuucaaaag cuagcccggg guu 23 <210> 2306 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2306 uuccugaagg ucaccucagu cuu 23 <210> 2307 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2307 aagaucuaug gaaaauuaau auu 23 <210> 2308 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2308 aagauccaga ucuauggaaa auu 23 <210> 2309 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2309 aaauccaaug cugucugaga auu 23 <210> 2310 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2310 auccugagca ccuuuaggaa auu 23 <210> 2311 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2311 agggaauggc aaggauccag guu 23 <210> 2312 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2312 agcugagggg aauggcaagg auu 23 <210> 2313 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2313 aucauuagcu gaggggaaug guu 23 <210> 2314 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2314 uuuucccccu uuaaagguuu uuu 23 <210> 2315 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2315 uagauauugg guuuuaaaca auu 23 <210> 2316 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2316 auacuucauc agaucuuaga guu 23 <210> 2317 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2317 auauacuuca ucagaucuua guu 23 <210> 2318 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2318 aauauacuuc aucagaucuu auu 23 <210> 2319 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2319 aaauauacuu caucagaucu uuu 23 <210> 2320 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2320 aaauaaaaaa uauacuucau cuu 23 <210> 2321 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2321 aaggacaaaa uggcaauaaa auu 23 <210> 2322 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2322 aaaggacaaa auggcaauaa auu 23 <210> 2323 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2323 aaaaggacaa aauggcaaua auu 23 <210> 2324 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2324 aucaaaggac aaaauggcaa uuu 23 <210> 2325 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2325 auuuagucaa cuucccaaua uuu 23 <210> 2326 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2326 ucaaguuuag ucaacuuccc auu 23 <210> 2327 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2327 uucaaguuua gucaacuucc cuu 23 <210> 2328 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2328 uuucaaguuu agucaacuuc cuu 23 <210> 2329 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2329 uagcuuccau uuauucacag uuu 23 <210> 2330 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2330 aaaguagcuu ccauuuauuc auu 23 <210> 2331 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2331 agucaaagua gcuuccauuu auu 23 <210> 2332 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2332 uagucaaagu agcuuccauu uuu 23 <210> 2333 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2333 ugaaacuagu caaaguagcu uuu 23 <210> 2334 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2334 augaaacuag ucaaaguagc uuu 23 <210> 2335 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2335 aaacuggaga aggagcacuc cuu 23 <210> 2336 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2336 acuuuucccc cuuuaaaggu uuu 23 <210> 2337 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2337 uccuuuuccc ccuuuaaagg uuu 23 <210> 2338 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2338 ucaaaggaca aaauggcaau auu 23 <210> 2339 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2339 uuuucaaguu uagucaacuu cuu 23 <210> 2340 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2340 uuuuucaagu uuagucaacu uuu 23 <210> 2341 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2341 ucugaaacua gucaaaguag cuu 23 <210> 2342 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2342 uguaggcugc acugagaguc auu 23 <210> 2343 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2343 aacugcauuu guggugggcg uuu 23 <210> 2344 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2344 agaagcuggu uauccacugg guu 23 <210> 2345 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2345 aaacaagucu gcuauuugau guu 23 <210> 2346 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2346 aggaacaagu cugcuauuug auu 23 <210> 2347 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2347 uuaacuuucu ucucuagccu guu 23 <210> 2348 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2348 uuuaacuuuc uucucuagcc uuu 23 <210> 2349 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2349 aauauugggc cugaaguugg uuu 23 <210> 2350 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2350 aacgucacca auaagaagcu cuu 23 <210> 2351 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2351 uuccacguca ccaauaagaa guu 23 <210> 2352 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2352 aguuccacgu caccaauaag auu 23 <210> 2353 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2353 uuucaguucc acgucaccaa uuu 23 <210> 2354 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2354 uuaaaaugca ucuggaacaa guu 23 <210> 2355 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2355 aguuaaaaug caucuggaac auu 23 <210> 2356 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2356 auaacucuuc aguguuucca guu 23 <210> 2357 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2357 aauaacucuu caguguuucc auu 23 <210> 2358 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2358 aucacacugg cgauaacucu uuu 23 <210> 2359 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2359 agucacacug gcgauaacuc uuu 23 <210> 2360 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2360 aguggugauu uuccauauaa cuu 23 <210> 2361 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2361 agucccuggg uuuuccagca cuu 23 <210> 2362 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2362 uggucccugg guuuuccagc auu 23 <210> 2363 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2363 auggucccug gguuuuccag cuu 23 <210> 2364 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2364 auuugauggu cccuggguuu uuu 23 <210> 2365 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2365 acuuugaugg ucccuggguu uuu 23 <210> 2366 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2366 aacuuugaug gucccugggu uuu 23 <210> 2367 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2367 acacuuugau ggucccuggg uuu 23 <210> 2368 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2368 aagguacaca gggucuccca cuu 23 <210> 2369 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2369 aguucccauu acuggcccag cuu 23 <210> 2370 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2370 auucaagugu ugucauuuuu guu 23 <210> 2371 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2371 acaugcuuca aguguuguca uuu 23 <210> 2372 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2372 augaaacacc augcuucaag uuu 23 <210> 2373 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2373 aaaugugaaa aucacaaauu uuu 23 <210> 2374 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2374 acacugggac auugaagcau uuu 23 <210> 2375 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2375 aagaauccug ucuugucauu uuu 23 <210> 2376 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2376 agagaaagaa cuauuccaua auu 23 <210> 2377 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2377 aggagaaaga acuauuccau auu 23 <210> 2378 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2378 aagcaggaga aagaacuauu cuu 23 <210> 2379 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2379 aaagcaggag aaagaacuau uuu 23 <210> 2380 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2380 aagugguagu gacaggaugc auu 23 <210> 2381 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2381 agagugguag ugacaggaug cuu 23 <210> 2382 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2382 acauuucaaa agcuagcccg guu 23 <210> 2383 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2383 accauuucaa aagcuagccc guu 23 <210> 2384 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2384 acugaagguc accucagucu uuu 23 <210> 2385 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2385 agugcuuccu gaaggucacc uuu 23 <210> 2386 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2386 aggccagauc cagaucuaug guu 23 <210> 2387 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2387 ugagcaccuu uaggaaaucc auu 23 <210> 2388 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2388 acugagcacc uuuaggaaau cuu 23 <210> 2389 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2389 uccuccugag caccuuuagg auu 23 <210> 2390 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2390 aaaggaucca gggguccucc auu 23 <210> 2391 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2391 acaaggaucc agggguccuc cuu 23 <210> 2392 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2392 agcaaggauc cagggguccu cuu 23 <210> 2393 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2393 aacuggagaa ggagcacucc guu 23 <210> 2394 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2394 aucagagcag ugcguccuuc uuu 23 <210> 2395 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2395 acccuuccgg gccaaucaga guu 23 <210> 2396 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2396 aacccuuccg ggccaaucag auu 23 <210> 2397 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2397 aaacccuucc gggccaauca guu 23 <210> 2398 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2398 aggaaggugc ggccuuuggc cuu 23 <210> 2399 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2399 auggcuggcu ucuccgcgag guu 23 <210> 2400 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2400 acgcccaugg cuggcuucuc cuu 23 <210> 2401 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2401 agcgcccaug gcuggcuucu cuu 23 <210> 2402 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2402 auguuucccu ccugguugau cuu 23 <210> 2403 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2403 acgagguucc uggcgagcag uuu 23 <210> 2404 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2404 accaggcgag guuccuggcg auu 23 <210> 2405 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2405 agaccaggcg agguuccugg cuu 23 <210> 2406 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2406 aaucaggacc aggcgagguu cuu 23 <210> 2407 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2407 ugagagucag ggugucacca uuu 23 <210> 2408 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2408 augagaguca gggugucacc auu 23 <210> 2409 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2409 ugcacugaga gucagggugu cuu 23 <210> 2410 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2410 agcugcacug agagucaggg uuu 23 <210> 2411 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2411 agcugguuau ccacugggcg guu 23 <210> 2412 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2412 agcucgaagu gcaccaggcg guu 23 <210> 2413 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2413 aggcucgaag ugcaccaggc guu 23 <210> 2414 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2414 aaggcucgaa gugcaccagg cuu 23 <210> 2415 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2415 ugaggcucga agugcaccag guu 23 <210> 2416 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2416 augaggcucg aagugcacca guu 23 <210> 2417 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2417 ugugaggcuc gaagugcacc auu 23 <210> 2418 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2418 augugaggcu cgaagugcac cuu 23 <210> 2419 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2419 aaugugaggc ucgaagugca cuu 23 <210> 2420 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2420 acaugugagg cucgaagugc auu 23 <210> 2421 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2421 agcaugugag gcucgaagug cuu 23 <210> 2422 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2422 ucgcauguga ggcucgaagu guu 23 <210> 2423 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2423 aucgcaugug aggcucgaag uuu 23 <210> 2424 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2424 agucgcaugu gaggcucgaa guu 23 <210> 2425 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2425 aggucgcaug ugaggcucga auu 23 <210> 2426 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2426 ucggucgcau gugaggcucg auu 23 <210> 2427 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2427 aucggucgca ugugaggcuc guu 23 <210> 2428 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2428 agucucgguc gcaugugagg cuu 23 <210> 2429 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2429 aacgccucag aaaggaucaa guu 23 <210> 2430 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2430 acuggaguug agauccgcca guu 23 <210> 2431 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2431 accuggaguu gagauccgcc auu 23 <210> 2432 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2432 aauccucugc auagacaucg cuu 23 <210> 2433 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2433 agaauccucu gcauagacau cuu 23 <210> 2434 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2434 aaagaauccu cugcauagac auu 23 <210> 2435 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2435 acaagaaucc ucugcauaga cuu 23 <210> 2436 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2436 accaagaauc cucugcauag auu 23 <210> 2437 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2437 ucccaagaau ccucugcaua guu 23 <210> 2438 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2438 aaucuggaac aagccaucac cuu 23 <210> 2439 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2439 acaucuggaa caagccauca cuu 23 <210> 2440 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2440 aaaugcaucu ggaacaagcc auu 23 <210> 2441 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2441 agguccacug ugguuaaaau guu 23 <210> 2442 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2442 auggguccac ugugguuaaa auu 23 <210> 2443 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2443 ucugggucca cugugguuaa auu 23 <210> 2444 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2444 aauacugccc aaagaguggu guu 23 <210> 2445 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2445 aaauacugcc caaagagugg uuu 23 <210> 2446 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2446 agcacaaaau acugcccaaa guu 23 <210> 2447 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2447 aagcacaaaa uacugcccaa auu 23 <210> 2448 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2448 acagcacaaa auacugccca auu 23 <210> 2449 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2449 uccagcacaa aauacugccc auu 23 <210> 2450 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2450 uuuccagcac aaaauacugc cuu 23 <210> 2451 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2451 uggguuuucc agcacaaaau auu 23 <210> 2452 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2452 auggguuuuc cagcacaaaa uuu 23 <210> 2453 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2453 uaauauucca ggacauacgg uuu 23 <210> 2454 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2454 auaauauucc aggacauacg guu 23 <210> 2455 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2455 aucuaauauu ccaggacaua cuu 23 <210> 2456 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2456 aaucuaauau uccaggacau auu 23 <210> 2457 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2457 acaucuaaua uuccaggaca uuu 23 <210> 2458 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2458 agcaucuaau auuccaggac auu 23 <210> 2459 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2459 aggcaucuaa uauuccagga cuu 23 <210> 2460 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2460 aaggcaucua auauuccagg auu 23 <210> 2461 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2461 aaaggcaucu aauauuccag guu 23 <210> 2462 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2462 aaaaggcauc uaauauucca guu 23 <210> 2463 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2463 ucucaguucu gaaacaccau guu 23 <210> 2464 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2464 aucucaguuc ugaaacacca uuu 23 <210> 2465 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2465 agucucaguu cugaaacacc auu 23 <210> 2466 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2466 aggucucagu ucugaaacac cuu 23 <210> 2467 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2467 ugaaucacuu uucuucuccu cuu 23 <210> 2468 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2468 ucacugaauc acuuuucuuc uuu 23 <210> 2469 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2469 aucacugaau cacuuuucuu cuu 23 <210> 2470 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2470 aaaaucacug aaucacuuuu cuu 23 <210> 2471 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2471 augaaaucac ugaaucacuu uuu 23 <210> 2472 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2472 acuuuaaagg uuuucaguag uuu 23 <210> 2473 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2473 acccuuuaaa gguuuucagu auu 23 <210> 2474 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2474 aucagaucuu agaguuauac auu 23 <210> 2475 <211> 25 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2475 ucaucagauc uuagaguuau asusu 25 <210> 2476 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2476 uucaucagau cuuagaguua uuu 23 <210> 2477 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2477 auucaucaga ucuuagaguu auu 23 <210> 2478 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2478 acuucaucag aucuuagagu uuu 23 <210> 2479 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2479 uacuucauca gaucuuagag uuu 23 <210> 2480 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2480 augaacccuu ccgggccaau cuu 23 <210> 2481 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2481 auuuggcccc gagcccaaag guu 23 <210> 2482 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2482 agccuuuggc cccgagccca auu 23 <210> 2483 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2483 aggccgcugg gggaaggugc guu 23 <210> 2484 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2484 uucuccgcga gguggcggcg guu 23 <210> 2485 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2485 aacaaagcgc gccagcgcgg auu 23 <210> 2486 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2486 agacaaagcg cgccagcgcg guu 23 <210> 2487 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2487 aggacaaagc gcgccagcgc guu 23 <210> 2488 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2488 acgcgaggag gacaaagcgc guu 23 <210> 2489 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2489 ugcgcgagga ggacaaagcg cuu 23 <210> 2490 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2490 uugcgcgagg aggacaaagc guu 23 <210> 2491 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2491 auugcgcgag gaggacaaag cuu 23 <210> 2492 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2492 aauugcgcga ggaggacaaa guu 23 <210> 2493 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2493 agauugcgcg aggaggacaa auu 23 <210> 2494 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2494 agggauugcg cgaggaggac auu 23 <210> 2495 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2495 acgggauugc gcgaggagga cuu 23 <210> 2496 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2496 accgggauug cgcgaggagg auu 23 <210> 2497 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2497 agccgggauu gcgcgaggag guu 23 <210> 2498 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2498 accgggccgg gauugcgcga guu 23 <210> 2499 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2499 acacccgggc cgggauugcg cuu 23 <210> 2500 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2500 accacccggg ccgggauugc guu 23 <210> 2501 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2501 agccacccgg gccgggauug cuu 23 <210> 2502 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2502 aaaccccgag ccacccgggc cuu 23 <210> 2503 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2503 acaaccccga gccacccggg cuu 23 <210> 2504 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2504 agcaaccccg agccacccgg guu 23 <210> 2505 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2505 agcccagcgc ggcaaccccg auu 23 <210> 2506 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2506 aucaggccca gcgcggcaac cuu 23 <210> 2507 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2507 agcggucagg cccagcgcgg cuu 23 <210> 2508 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2508 aaccgcgguc aggcccagcg cuu 23 <210> 2509 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2509 acgccaccgc ggucaggccc auu 23 <210> 2510 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2510 agcgccaccg cggucaggcc cuu 23 <210> 2511 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2511 agcaguaacc auguuucccu cuu 23 <210> 2512 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2512 acgagcagua accauguuuc cuu 23 <210> 2513 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2513 agcgagcagu aaccauguuu cuu 23 <210> 2514 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2514 uggcgagcag uaaccauguu uuu 23 <210> 2515 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2515 auggcgagca guaaccaugu uuu 23 <210> 2516 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2516 acuggcgagc aguaaccaug uuu 23 <210> 2517 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2517 agguuccugg cgagcaguaa cuu 23 <210> 2518 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2518 ucaccaucgc aggucaggga auu 23 <210> 2519 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2519 aaggguguca ccaucgcagg uuu 23 <210> 2520 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2520 aguccuuugu guaggcugca cuu 23 <210> 2521 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2521 agguccuuug uguaggcugc auu 23 <210> 2522 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2522 asagguccuu uguguaggcu guu 23 <210> 2523 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2523 aguagguccu uuguguaggc uuu 23 <210> 2524 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2524 uaguaggucc uuuguguagg cuu 23 <210> 2525 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2525 auaguagguc cuuuguguag guu 23 <210> 2526 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2526 aguaguaggu ccuuugugua guu 23 <210> 2527 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2527 agcaguagua gguccuuugu guu 23 <210> 2528 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2528 ugauaggcag uaguaggucc uuu 23 <210> 2529 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2529 uugauaggca guaguagguc cuu 23 <210> 2530 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2530 uuuugauagg caguaguagg uuu 23 <210> 2531 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2531 acguuuugau aggcaguagu auu 23 <210> 2532 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2532 aggcguuuug auaggcagua guu 23 <210> 2533 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2533 auggugggcg uuuugauagg cuu 23 <210> 2534 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2534 auugugcacu gcauuugugg uuu 23 <210> 2535 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2535 aacuugugca cugcauuugu guu 23 <210> 2536 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2536 ugcacuugug cacugcauuu guu 23 <210> 2537 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2537 aucugcacuu gugcacugca uuu 23 <210> 2538 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2538 ugcacucugc acuugugcac uuu 23 <210> 2539 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2539 agccgugcac ucugcacuug uuu 23 <210> 2540 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2540 aggccgugca cucugcacuu guu 23 <210> 2541 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2541 auccaggccg ugcacucugc auu 23 <210> 2542 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2542 uaucuccagg ccgugcacuc uuu 23 <210> 2543 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2543 auaucuccag gccgugcacu cuu 23 <210> 2544 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2544 agucccugcc cucuaucucc auu 23 <210> 2545 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2545 aguagggcug ugacuucagg auu 23 <210> 2546 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2546 acgguagggc ugugacuuca guu 23 <210> 2547 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2547 aggcgguagg gcugugacuu cuu 23 <210> 2548 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2548 acgucucggu cgcaugugag guu 23 <210> 2549 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2549 aacgucucgg ucgcauguga guu 23 <210> 2550 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2550 agacgucucg gucgcaugug auu 23 <210> 2551 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2551 aggacgucuc ggucgcaugu guu 23 <210> 2552 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2552 aaggacgucu cggucgcaug uuu 23 <210> 2553 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2553 aaugaggacg ucucggucgc auu 23 <210> 2554 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2554 ugaugaggac gucucggucg cuu 23 <210> 2555 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2555 uauuugauga ggacgucucg guu 23 <210> 2556 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2556 auauuugaug aggacgucuc guu 23 <210> 2557 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2557 ugcuauuuga ugaggacguc uuu 23 <210> 2558 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2558 aagucugcua uuugaugagg auu 23 <210> 2559 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2559 acaagucugc uauuugauga guu 23 <210> 2560 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2560 ucaagaaugg gcuggugucu guu 23 <210> 2561 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2561 aucaagaaug ggcugguguc uuu 23 <210> 2562 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2562 aaucaagaau gggcuggugu cuu 23 <210> 2563 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2563 aaaaggauca agaaugggcu guu 23 <210> 2564 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2564 aucagaaagg aucaagaaug guu 23 <210> 2565 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2565 aucaucccaa gaauccucug cuu 23 <210> 2566 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2566 uaagaagcuc aucccaagaa uuu 23 <210> 2567 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2567 aaauaagaag cucaucccaa guu 23 <210> 2568 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2568 aaccaauaag aagcucaucc cuu 23 <210> 2569 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2569 ucaccaauaa gaagcucauc cuu 23 <210> 2570 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2570 aaucacccuu uucaguucca cuu 23 <210> 2571 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2571 acaucacccu uuucaguucc auu 23 <210> 2572 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotid <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2572 agccaucacc cuuuucaguu cuu 23 <210> 2573 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2573 acaagccauc acccuuuuca guu 23 <210> 2574 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2574 aacaagccau cacccuuuuc auu 23 <210> 2575 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2575 aaacaagcca ucacccuuuu cuu 23 <210> 2576 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2576 agaacaagcc aucacccuuu uuu 23 <210> 2577 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2577 aacaccggug ucugggucca cuu 23 <210> 2578 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2578 ugacaccggu gucugggucc auu 23 <210> 2579 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2579 augacaccgg ugucuggguc cuu 23 <210> 2580 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2580 ucaugacacc ggugucuggg uuu 23 <210> 2581 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2581 acucaugaca ccggugucug guu 23 <210> 2582 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2582 uuccugcuca ugacaccggu guu 23 <210> 2583 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2583 agguuccuuc cugcucauga cuu 23 <210> 2584 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2584 aagcgguucc uuccugcuca uuu 23 <210> 2585 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2585 uguuuccagc gguuccuucc uuu 23 <210> 2586 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2586 auguuuccag cgguuccuuc cuu 23 <210> 2587 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2587 aguguuucca gcgguuccuu cuu 23 <210> 2588 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2588 agguucccau uacuggccca guu 23 <210> 2589 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2589 uacgguuccc auuacuggcc cuu 23 <210> 2590 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2590 auacgguucc cauuacuggc cuu 23 <210> 2591 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2591 aauacgguuc ccauuacugg cuu 23 <210> 2592 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2592 acauacgguu cccauuacug guu 23 <210> 2593 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2593 aacauacggu ucccauuacu guu 23 <210> 2594 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2594 agacauacgg uucccauuac uuu 23 <210> 2595 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2595 uuccaggaca uacgguuccc auu 23 <210> 2596 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2596 uauuccagga cauacgguuc cuu 23 <210> 2597 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2597 uuuaaaaggc aucuaauauu cuu 23 <210> 2598 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2598 agaacauuuu uaaaaggcau cuu 23 <210> 2599 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2599 uagaggucuc aguucugaaa cuu 23 <210> 2600 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2600 auguagaggu cucaguucug auu 23 <210> 2601 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2601 agaaaaugua gaggucucag uuu 23 <210> 2602 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2602 aagaaaaugu agaggucuca guu 23 <210> 2603 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2603 aaagaaaaug uagaggucuc auu 23 <210> 2604 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2604 agacgaaaaa ugugaaaauc auu 23 <210> 2605 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2605 aagacgaaaa augugaaaau cuu 23 <210> 2606 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2606 aaagacgaaa aaugugaaaa uuu 23 <210> 2607 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2607 aaaaagacga aaaaugugaa auu 23 <210> 2608 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2608 acaaaagacg aaaaauguga auu 23 <210> 2609 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2609 uccaaaagac gaaaaaugug auu 23 <210> 2610 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2610 aguccaaaag acgaaaaaug uuu 23 <210> 2611 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2611 aagaagucca aaagacgaaa auu 23 <210> 2612 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2612 acagaagucc aaaagacgaa auu 23 <210> 2613 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2613 accagaaguc caaaagacga auu 23 <210> 2614 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2614 aaccagaagu ccaaaagacg auu 23 <210> 2615 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2615 aagacaccag aaguccaaaa guu 23 <210> 2616 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2616 auugagacac cagaagucca auu 23 <210> 2617 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2617 acauugagac accagaaguc cuu 23 <210> 2618 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2618 agcauugaga caccagaagu cuu 23 <210> 2619 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2619 ugaagcauug agacaccaga auu 23 <210> 2620 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2620 uuugcacugg gacauugaag cuu 23 <210> 2621 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2621 uuacuuuuug cacugggaca uuu 23 <210> 2622 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2622 uuuacuuuuu gcacugggac auu 23 <210> 2623 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2623 auuuacuuuu ugcacuggga cuu 23 <210> 2624 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2624 ucuuuacuuu uugcacuggg auu 23 <210> 2625 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2625 uauuucuuua cuuuuugcac uuu 23 <210> 2626 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2626 auuauugaga cuauauuucu uuu 23 <210> 2627 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2627 uaaguuauug agacuauauu uuu 23 <210> 2628 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2628 acuaaguuau ugagacuaua uuu 23 <210> 2629 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2629 uacuaaguua uugagacuau auu 23 <210> 2630 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2630 auacuaaguu auugagacua uuu 23 <210> 2631 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2631 acuacuaagu uauugagacu auu 23 <210> 2632 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2632 uccuacuaag uuauugagac uuu 23 <210> 2633 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2633 aaaguccuac uaaguuauug auu 23 <210> 2634 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2634 ugaaguccua cuaaguuauu guu 23 <210> 2635 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2635 acugaagucc uacuaaguua uuu 23 <210> 2636 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2636 uuacugaagu ccuacuaagu uuu 23 <210> 2637 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2637 auuacugaag uccuacuaag uuu 23 <210> 2638 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2638 aacuuacuga aguccuacua auu 23 <210> 2639 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2639 ugacuuacug aaguccuacu auu 23 <210> 2640 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2640 augacuuacu gaaguccuac uuu 23 <210> 2641 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2641 aagugacuua cugaaguccu auu 23 <210> 2642 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2642 agaauccugu cuugucauuu auu 23 <210> 2643 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2643 aacggggagu uuucagaauc cuu 23 <210> 2644 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2644 aaacggggag uuuucagaau cuu 23 <210> 2645 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2645 uuaaacgggg aguuuucaga auu 23 <210> 2646 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2646 auuaaacggg gaguuuucag auu 23 <210> 2647 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2647 aguuaaacgg ggaguuuuca guu 23 <210> 2648 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2648 aaguuaaacg gggaguuuuc auu 23 <210> 2649 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2649 aucaguuaaa cggggaguuu uuu 23 <210> 2650 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2650 auaaucaguu aaacggggag uuu 23 <210> 2651 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2651 aauaaucagu uaaacgggga guu 23 <210> 2652 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2652 acauaaucag uuaaacgggg auu 23 <210> 2653 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2653 uccauaauca guuaaacggg guu 23 <210> 2654 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2654 auaaacggag aagcaggaga auu 23 <210> 2655 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2655 aauaaacgga gaagcaggag auu 23 <210> 2656 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2656 agauaaacgg agaagcagga guu 23 <210> 2657 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2657 auagauaaac ggagaagcag guu 23 <210> 2658 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2658 uugguagaua aacggagaag cuu 23 <210> 2659 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2659 auugguagau aaacggagaa guu 23 <210> 2660 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2660 ucuugguaga uaaacggaga auu 23 <210> 2661 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2661 aucuugguag auaaacggag auu 23 <210> 2662 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2662 acucuuggua gauaaacgga guu 23 <210> 2663 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2663 agcucuuggu agauaaacgg auu 23 <210> 2664 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2664 ugcgcucuug guagauaaac guu 23 <210> 2665 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2665 aucugcgcuc uugguagaua auu 23 <210> 2666 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2666 aagucugcgc ucuugguaga uuu 23 <210> 2667 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2667 ugcaagucug cgcucuuggu auu 23 <210> 2668 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2668 augcaagucu gcgcucuugg uuu 23 <210> 2669 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2669 agaugcaagu cugcgcucuu guu 23 <210> 2670 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2670 aggaugcaag ucugcgcucu uuu 23 <210> 2671 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2671 acaggaugca agucugcgcu cuu 23 <210> 2672 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2672 ugacaggaug caagucugcg cuu 23 <210> 2673 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2673 augacaggau gcaagucugc guu 23 <210> 2674 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2674 uagugacagg augcaagucu guu 23 <210> 2675 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2675 augguaguga caggaugcaa guu 23 <210> 2676 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2676 acgaguggua gugacaggau guu 23 <210> 2677 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2677 uaacgagugg uagugacagg auu 23 <210> 2678 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2678 auaacgagug guagugacag guu 23 <210> 2679 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2679 ucuaacgagu gguagugaca guu 23 <210> 2680 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2680 aucuaacgag ugguagugac auu 23 <210> 2681 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2681 auuucucuaa cgagugguag uuu 23 <210> 2682 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(2) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2682 ucuuccagcc cacccacucu uuu 23 <210> 2683 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2683 aggcaauaac acauucuagg auu 23 <210> 2684 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2684 agggcaauaa cacauucuag guu 23 <210> 2685 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2685 aaacaggggc aauaacacau uuu 23 <210> 2686 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2686 aaugaacagg ggcaauaaca cuu 23 <210> 2687 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2687 acucaugaac aggggcaaua auu 23 <210> 2688 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2688 uaccucauga acaggggcaa uuu 23 <210> 2689 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2689 aggugcaauu uaauuuucau uuu 23 <210> 2690 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2690 agggugcaau uuaauuuuca uuu 23 <210> 2691 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2691 auuuggggug caauuuaauu uuu 23 <210> 2692 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2692 auauuugggg ugcaauuuaa uuu 23 <210> 2693 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2693 aauauuuggg gugcaauuua auu 23 <210> 2694 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2694 agccauauuu ggggugcaau uuu 23 <210> 2695 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2695 aagccauauu uggggugcaa uuu 23 <210> 2696 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2696 aaaguggcau uccagccaua uuu 23 <210> 2697 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2697 aaaaagggaa guggcauucc auu 23 <210> 2698 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2698 aggcuugaga agaaaaggga auu 23 <210> 2699 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2699 auagcccggg gcuugagaag auu 23 <210> 2700 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2700 aagcuagccc ggggcuugag auu 23 <210> 2701 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2701 ucuuuaugcc auuucaaaag cuu 23 <210> 2702 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2702 aagucuuuau gccauuucaa auu 23 <210> 2703 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2703 aaccucaguc uuuaugccau uuu 23 <210> 2704 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2704 aucaccucag ucuuuaugcc auu 23 <210> 2705 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2705 aggucaccuc agucuuuaug cuu 23 <210> 2706 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2706 aauuaauauc ugcagugcuu cuu 23 <210> 2707 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2707 aauccuccug agcaccuuua guu 23 <210> 2708 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2708 aaaccauccu ccugagcacc uuu 23 <210> 2709 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2709 aacaaccauc cuccugagca cuu 23 <210> 2710 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2710 aaugacuaca caaccauccu cuu 23 <210> 2711 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2711 acaugacuac acaaccaucc uuu 23 <210> 2712 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2712 uccaugacua cacaaccauc cuu 23 <210> 2713 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2713 agguccucca ugacuacaca auu 23 <210> 2714 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2714 agauccaggg guccuccaug auu 23 <210> 2715 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2715 acgucauuag cugaggggaa uuu 23 <210> 2716 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2716 uccgucauua gcugagggga auu 23 <210> 2717 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2717 auccgucauu agcugagggg auu 23 <210> 2718 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2718 aagcacuccg ucauuagcug auu 23 <210> 2719 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2719 aacagaauuc agaacuuuuu cuu 23 <210> 2720 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2720 uccuccacag aauucagaac uuu 23 <210> 2721 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2721 aguagucuau cugaaaucac uuu 23 <210> 2722 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2722 uuucaguagu cuaucugaaa uuu 23 <210> 2723 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2723 agguuuucag uagucuaucu guu 23 <210> 2724 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2724 uuaaagguuu ucaguagucu auu 23 <210> 2725 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2725 uuuaaagguu uucaguaguc uuu 23 <210> 2726 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2726 aaacugacau augcuuuccu uuu 23 <210> 2727 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2727 acaacugaca uaugcuuucc uuu 23 <210> 2728 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2728 aacaacugac auaugcuuuc cuu 23 <210> 2729 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2729 uaaacaacug acauaugcuu uuu 23 <210> 2730 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2730 uuaaacaacu gacauaugcu uuu 23 <210> 2731 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2731 uuuaaacaac ugacauaugc uuu 23 <210> 2732 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2732 aaaaauagau auuggguuuu auu 23 <210> 2733 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2733 uuaaaaaaua gauauugggu uuu 23 <210> 2734 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2734 uagaguuaua caaucaguua auu 23 <210> 2735 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2735 uuagaguuau acaaucaguu auu 23 <210> 2736 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2736 ucuuagaguu auacaaucag uuu 23 <210> 2737 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2737 aucuuagagu uauacaauca guu 23 <210> 2738 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2738 agaucuuaga guuauacaau cuu 23 <210> 2739 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2739 auaaucaaag gacaaaaugg cuu 23 <210> 2740 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2740 ucccaauaua aucaaaggac auu 23 <210> 2741 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2741 ugaaauuaca auauugggcc uuu 23 <210> 2742 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2742 uuccauauaa cuuucguucu guu 23 <210> 2743 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2743 augguuaaaa ugcaucugga auu 23 <210> 2744 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2744 auccacugug guuaaaaugc auu 23 <210> 2745 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2745 aggaagcugg uuauccacug guu 23 <210> 2746 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2746 uaacucuuca guguuuccag cuu 23 <210> 2747 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2747 acgauaacuc uucaguguuu cuu 23 <210> 2748 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2748 uggcgauaac ucuucagugu uuu 23 <210> 2749 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2749 uuccauaauc aguuaaacgg guu 23 <210> 2750 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2750 augcuucaag uguugucauu uuu 23 <210> 2751 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2751 ugaaacacca ugcuucaagu guu 23 <210> 2752 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2752 agaaagaacu auuccauaau cuu 23 <210> 2753 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2753 aagaaagaac uauuccauaa uuu 23 <210> 2754 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2754 aauugaagca uugagacacc auu 23 <210> 2755 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2755 uuuucagaau ccugucuugu cuu 23 <210> 2756 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2756 auuuuaaaca acugacauau guu 23 <210> 2757 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2757 aauauugggu uuuaaacaac uuu 23 <210> 2758 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2758 uagauauugg guuuuaaaca auu 23 <210> 2759 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2759 aaauaaaaaa uauacuucau cuu 23 <210> 2760 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2760 aaggacaaaa uggcaauaaa auu 23 <210> 2761 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2761 aucaaaggac aaaauggcaa uuu 23 <210> 2762 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2762 auuuagucaa cuucccaaua uuu 23 <210> 2763 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2763 uuucaaguuu agucaacuuc cuu 23 <210> 2764 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2764 uagcuuccau uuauucacag uuu 23 <210> 2765 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2765 agugucugag uaagcaaucu guu 23 <210> 2766 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2766 acacuggcga uaacucuuca guu 23 <210> 2767 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2767 auaacuuucg uucugaaggg uuu 23 <210> 2768 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2768 acuuucguuc ugaaggguca cuu 23 <210> 2769 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2769 uccauauaac uuucguucug auu 23 <210> 2770 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2770 auuccacguc accaauaaga auu 23 <210> 2771 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2771 auggugauuu uccauauaac uuu 23 <210> 2772 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2772 uauaacuuuc guucugaagg guu 23 <210> 2773 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2773 auauaacuuu cguucugaag guu 23 <210> 2774 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2774 aauauaacuu ucguucugaa guu 23 <210> 2775 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2775 acaauauugg gccugaaguu guu 23 <210> 2776 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2776 agauaacucu ucaguguuuc cuu 23 <210> 2777 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2777 uuacaauauu gggccugaag uuu 23 <210> 2778 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2778 ugaaguuggu ugcuuuaacu uuu 23 <210> 2779 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2779 auuacaauau ugggccugaa guu 23 <210> 2780 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2780 aucugaguaa gcaaucuggu cuu 23 <210> 2781 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2781 aagaacuauu ccauaaucag uuu 23 <210> 2782 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2782 aagaguggug auuuuccaua uuu 23 <210> 2783 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2783 aacugggaca uugaagcauu guu 23 <210> 2784 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2784 uugcacuggg acauugaagc auu 23 <210> 2785 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2785 ucagaauccu gucuugucau uuu 23 <210> 2786 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2786 auauacuuca ucagaucuua guu 23 <210> 2787 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2787 auugaagcau ugagacacca guu 23 <210> 2788 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2788 agacauugaa gcauugagac auu 23 <210> 2789 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2789 aagauccaga ucuauggaaa auu 23 <210> 2790 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2790 auuucguucu gaagggucac auu 23 <210> 2791 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2791 ucguucugaa gggucacacu guu 23 <210> 2792 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2792 auuccagcca uauuuggggu guu 23 <210> 2793 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2793 augggacauu gaagcauuga guu 23 <210> 2794 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2794 agggaguuuu cagaauccug uuu 23 <210> 2795 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2795 ugaggggaau ggcaaggauc cuu 23 <210> 2796 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2796 auggaaaauu aauaucugca guu 23 <210> 2797 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2797 aaauauacuu caucagaucu uuu 23 <210> 2798 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2798 agucggaaca agucugcuau uuu 23 <210> 2799 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2799 aaccaugcuu caaguguugu cuu 23 <210> 2800 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2800 aggaaaucca augcugucug auu 23 <210> 2801 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2801 acaaagagug gugauuuucc auu 23 <210> 2802 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2802 uuaggaaauc caaugcuguc uuu 23 <210> 2803 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 2803 aaagaacuau uccauaauca guu 23 <210> 2804 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2804 augcuucaau gucccaguuu 20 <210> 2805 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2805 gaacgaaagu uauauggaau 20 <210> 2806 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2806 gauugcuuac ucagacacuu 20 <210> 2807 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2807 caaugcuuca augucccauu 20 <210> 2808 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2808 guuuaaaacc caauaucuau 20 <210> 2809 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2809 cuucaauguc ccagugcaau 20 <210> 2810 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2810 agacagcauu ggauuuccuu 20 <210> 2811 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2811 gaaaaucacc acucuuuguu 20 <210> 2812 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2812 acagcauugg auuuccuaau 20 <210> 2813 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2813 aggauucuga aaacucccuu 20 <210> 2814 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2814 caacacuuga agcaugguuu 20 <210> 2815 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2815 cuguuuaaaa cccaauaucu 20 <210> 2816 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2816 cgcuucaaug ucccagugca 20 <210> 2817 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2817 ccagacagca uuggauuucc 20 <210> 2818 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2818 cggaaaauca ccacucuuug 20 <210> 2819 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2819 ggacagcauu ggauuuccua 20 <210> 2820 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2820 gcaggauucu gaaaacuccc 20 <210> 2821 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2821 gauggcuugu uccagauguu 20 <210> 2822 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2822 uccuggaaua uuagaugcuu 20 <210> 2823 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2823 ucuaagaucu gaugaaguau 20 <210> 2824 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2824 cccuggaaua uuagaugccu 20 <210> 2825 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2825 gcucuaagau cugaugaagu 20 <210> 2826 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2826 cguccuggaa uauuagaugc 20 <210> 2827 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2827 caacucuaag aucugaugaa 20 <210> 2828 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2828 ggaagaaaag ugauucagug 20 <210> 2829 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2829 guccaggaau auuagaugcc 20 <210> 2830 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2830 gugcuggaau auuagaugcc 20 <210> 2831 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2831 uccucgaaua uuagaugccu 20 <210> 2832 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2832 ucguggaaua uuagaugccu 20 <210> 2833 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2833 acacuaagau cugaugaagu 20 <210> 2834 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2834 agucuaagau cugaugaagu 20 <210> 2835 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2835 agucagcauu ggauuuccua 20 <210> 2836 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2836 acacagcauu ggauuuccua 20 <210> 2837 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2837 ugauggcuug uuccagaugc 20 <210> 2838 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2838 gauggcuugu uccagaugca 20 <210> 2839 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2839 cucagacagc auuggauuuc 20 <210> 2840 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2840 ugccauuuug uccuuugauu 20 <210> 2841 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2841 ccauuuuguc cuuugauuau 20 <210> 2842 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2842 uuuucacauu uuucgucuuu 20 <210> 2843 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2843 acucuaagau cugaugaauu 20 <210> 2844 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2844 aagaaaagug auucagugau 20 <210> 2845 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2845 auauuagaug ccuuuuaaau 20 <210> 2846 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2846 gaaagcauau gucaguuguu 20 <210> 2847 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2847 cauuuugucc uuugauuauu 20 <210> 2848 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2848 auauagucuc aauaacuuau 20 <210> 2849 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2849 ccaagagcgc agacuugcau 20 <210> 2850 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2850 ugccuuuuaa aaauguucuu 20 <210> 2851 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2851 guccuggaau auuagauguu 20 <210> 2852 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2852 ccuaagaucu gaugaaguau 20 <210> 2853 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2853 uagcagacuu guuccgacuu 20 <210> 2854 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2854 ccguuuaacu gauuauggau 20 <210> 2855 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2855 gacaacacuu gaagcauguu 20 <210> 2856 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2856 uugccauuuu guccuuugau 20 <210> 2857 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2857 uaacucuaag aucugaugau 20 <210> 2858 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2858 gucucaaugc uucaauguuu 20 <210> 2859 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2859 gugauggcuu guuccggaug 20 <210> 2860 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2860 gugauggcuu guugcagaug 20 <210> 2861 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2861 cagaacgaaa guuaugugga 20 <210> 2862 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2862 cagaacgaaa guuguaugga 20 <210> 2863 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2863 uauguccugg aauauaagau 20 <210> 2864 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2864 uauguccugg aauguuagau 20 <210> 2865 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2865 auguccugga auauuggaug 20 <210> 2866 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2866 auguccugga auaauagaug 20 <210> 2867 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2867 uguccuggaa uauuaaaugc 20 <210> 2868 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2868 uguccuggaa uauaagaugc 20 <210> 2869 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2869 ccuggaauau uaggugccuu 20 <210> 2870 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2870 ccuggaauau uggaugccuu 20 <210> 2871 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2871 uccuggaaua uuagaagccu 20 <210> 2872 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2872 uccuggaaua uuaaaugccu 20 <210> 2873 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2873 ccuggaauau uagauaccuu 20 <210> 2874 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2874 cuggaauauu agauggcuuu 20 <210> 2875 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2875 cuggaauauu agaagccuuu 20 <210> 2876 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2876 gaauauuaga ugccuauuaa 20 <210> 2877 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2877 gaauauuaga ugcguuuuaa 20 <210> 2878 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2878 gaugccuuuu aaaaaaguuc 20 <210> 2879 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2879 gaugccuuuu aaagauguuc 20 <210> 2880 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2880 gauuuucaca uuuuuggucu 20 <210> 2881 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2881 gauuuucaca uuuaucgucu 20 <210> 2882 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2882 cucaaugcuu caaugaccca 20 <210> 2883 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2883 cucaaugcuu caaaguccca 20 <210> 2884 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2884 caaugcuuca augucgcagu 20 <210> 2885 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2885 caaugcuuca augacccagu 20 <210> 2886 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2886 aaauauaguc ucaaugacuu 20 <210> 2887 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2887 aaauauaguc ucaguaacuu 20 <210> 2888 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2888 gcaggauucu gaaaaguccc 20 <210> 2889 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2889 gcaggauucu gaagacuccc 20 <210> 2890 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2890 uaccaagagc gcagaguugc 20 <210> 2891 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2891 uaccaagagc gcaaacuugc 20 <210> 2892 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2892 aggaaagcau augucgguug 20 <210> 2893 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2893 aggaaagcau augacaguug 20 <210> 2894 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2894 guuuaaaacc caaaaucuau 20 <210> 2895 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2895 guuuaaaacc cgauaucuau 20 <210> 2896 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2896 uuaacugauu guauagcucu 20 <210> 2897 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2897 uuaacugauu guaaaacucu 20 <210> 2898 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2898 uaacucuaag aucuggugaa 20 <210> 2899 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2899 uaacucuaag aucagaugaa 20 <210> 2900 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2900 acucuaagau cugauaaagu 20 <210> 2901 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2901 acucuaagau cuggugaagu 20 <210> 2902 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2902 uauugccauu uugucguuug 20 <210> 2903 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2903 uauugccauu uugaccuuug 20 <210> 2904 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2904 gccauuuugu ccuuuaauua 20 <210> 2905 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2905 gccauuuugu ccuaugauua 20 <210> 2906 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2906 uuuuucaagu uuagucaacu uuu 23 <210> 2907 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2907 aacugggaca uugaagcauu u 21 <210> 2908 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2908 uuccauauaa cuuucguucu u 21 <210> 2909 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2909 agugucugag uaagcaaucu u 21 <210> 2910 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2910 auuacaauau ugggccugaa gug 23 <210> 2911 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2911 aacugggaca uugaagcauu gug 23 <210> 2912 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2912 uuccauauaa cuuucguucu gug 23 <210> 2913 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2913 uuucaaguuu agucaacuuc cug 23 <210> 2914 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2914 aggaagcugg uuauccacug gug 23 <210> 2915 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2915 auauacuuca ucagaucuua gug 23 <210> 2916 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2916 agugucugag uaagcaaucu gug 23 <210> 2917 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2917 aacugggaca uugaagcauu gag 23 <210> 2918 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2918 auuacaauau ugggccugaa g 21 <210> 2919 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2919 aacugggaca uugaagcauu g 21 <210> 2920 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2920 uuccauauaa cuuucguucu g 21 <210> 2921 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2921 uuucaaguuu agucaacuuc c 21 <210> 2922 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2922 aggaagcugg uuauccacug g 21 <210> 2923 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2923 auauacuuca ucagaucuua g 21 <210> 2924 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2924 agugucugag uaagcaaucu g 21 <210> 2925 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2925 augggacauu gaagcauugu u 21 <210> 2926 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2926 uagauauugg guuuuaaacu u 21 <210> 2927 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2927 uugcacuggg acauugaagu u 21 <210> 2928 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2928 aggaaaucca augcugucuu u 21 <210> 2929 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2929 acaaagagug gugauuuucu u 21 <210> 2930 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2930 uuaggaaauc caaugcuguu u 21 <210> 2931 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2931 agggaguuuu cagaauccuu u 21 <210> 2932 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2932 aaccaugcuu caaguguugu u 21 <210> 2933 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2933 augggacauu gaagcauuga g 21 <210> 2934 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2934 uagauauugg guuuuaaaca a 21 <210> 2935 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2935 uugcacuggg acauugaagc a 21 <210> 2936 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2936 aggaaaucca augcugucug a 21 <210> 2937 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2937 acaaagagug gugauuuucc a 21 <210> 2938 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2938 uuaggaaauc caaugcuguc u 21 <210> 2939 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2939 agggaguuuu cagaauccug u 21 <210> 2940 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2940 aaccaugcuu caaguguugu c 21 <210> 2941 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2941 uagauauugg guuuuaaaca guu 23 <210> 2942 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2942 uugcacuggg acauugaagc guu 23 <210> 2943 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2943 aggaaaucca augcugucug guu 23 <210> 2944 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2944 acaaagagug gugauuuucc guu 23 <210> 2945 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2945 uuaggaaauc caaugcuguc cuu 23 <210> 2946 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2946 agggaguuuu cagaauccug cuu 23 <210> 2947 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2947 acaucuggaa caagccaucu u 21 <210> 2948 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2948 agcaucuaau auuccaggau u 21 <210> 2949 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2949 aggcaucuaa uauuccaggu u 21 <210> 2950 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2950 uacuucauca gaucuuagau u 21 <210> 2951 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2951 aaggcaucua auauuccagu u 21 <210> 2952 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2952 acaucuggaa caagccauca c 21 <210> 2953 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2953 agcaucuaau auuccaggac a 21 <210> 2954 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2954 aggcaucuaa uauuccagga c 21 <210> 2955 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2955 uacuucauca gaucuuagag u 21 <210> 2956 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2956 aaggcaucua auauuccagg a 21 <210> 2957 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2957 aaggcaucua auauuccagg guu 23 <210> 2958 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2958 uacuucauca gaucuuagag cuu 23 <210> 2959 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2959 agcaucuaau auuccaggac guu 23 <210> 2960 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2960 auucaucaga ucuuagaguu guu 23 <210> 2961 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2961 ucacugaauc acuuuucuuc cuu 23 <210> 2962 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2962 aggcaucuaa uauuccugga cuu 23 <210> 2963 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2963 aggcaucuaa uauuccagca cuu 23 <210> 2964 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2964 aaggcaucua auauucgagg auu 23 <210> 2965 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2965 aaggcaucua auauuccacg auu 23 <210> 2966 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2966 uacuucauca gaucuuagug uuu 23 <210> 2967 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2967 uacuucauca gaucuuagac uuu 23 <210> 2968 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2968 uuaggaaauc caaugcugac uuu 23 <210> 2969 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2969 uuaggaaauc caaugcugug uuu 23 <210> 2970 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2970 ugcaucugga acaagccauc auu 23 <210> 2971 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2971 augcaucugg aacaagccau cuu 23 <210> 2972 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2972 agaaauccaa ugcugucuga guu 23 <210> 2973 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2973 uaaucaaagg acaaaauggc auu 23 <210> 2974 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2974 uauaaucaaa ggacaaaaug guu 23 <210> 2975 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2975 aagacgaaaa augugaaaau c 21 <210> 2976 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2976 uuuaaaaggc aucuaauauu c 21 <210> 2977 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2977 acaacugaca uaugcuuucc u 21 <210> 2978 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2978 auaaucaaag gacaaaaugg c 21 <210> 2979 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2979 uaaguuauug agacuauauu u 21 <210> 2980 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2980 ugcaagucug cgcucuuggu a 21 <210> 2981 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2981 agaacauuuu uaaaaggcau c 21 <210> 2982 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2982 acaucuaaua uuccaggaca u 21 <210> 2983 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2983 aagacgaaaa augugaaaau u 21 <210> 2984 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2984 uuuaaaaggc aucuaauauu u 21 <210> 2985 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2985 acaacugaca uaugcuuucu u 21 <210> 2986 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2986 auaaucaaag gacaaaaugu u 21 <210> 2987 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2987 ugcaagucug cgcucuuggu u 21 <210> 2988 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2988 agaacauuuu uaaaaggcau u 21 <210> 2989 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2989 acaucuaaua uuccaggacu u 21 <210> 2990 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2990 uacuucauca gaucuuaggu u 21 <210> 2991 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2991 uagauauugg guuuuaaaca acu 23 <210> 2992 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2992 uuccauauaa cuuucguucu gaa 23 <210> 2993 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2993 auauacuuca ucagaucuua gag 23 <210> 2994 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2994 acaaagagug gugauuuucc aua 23 <210> 2995 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2995 auucaucaga ucuuagaguu a 21 <210> 2996 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2996 ucacugaauc acuuuucuuc u 21 <210> 2997 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2997 aagacgaaaa augugaaaau cac 23 <210> 2998 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2998 auucaucaga ucuuagaguu aua 23 <210> 2999 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 2999 ucacugaauc acuuuucuuc ucc 23 <210> 3000 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3000 auucaucaga ucuuagaguu u 21 <210> 3001 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3001 ucacugaauc acuuuucuuu u 21 <210> 3002 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3002 ugcaagucug cgcucuuggu aga 23 <210> 3003 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3003 agucggaaca agucugcuau u 21 <210> 3004 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3004 uccauaauca guuaaacggg g 21 <210> 3005 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3005 acaugcuuca aguguuguca u 21 <210> 3006 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3006 ucaaaggaca aaauggcaau a 21 <210> 3007 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3007 ucaucagauc uuagaguuau a 21 <210> 3008 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3008 aacauugaag cauugagaca c 21 <210> 3009 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3009 uccauaauca guuaaacggu u 21 <210> 3010 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3010 acaugcuuca aguguugucu u 21 <210> 3011 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3011 ucaaaggaca aaauggcaau u 21 <210> 3012 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3012 ucaucagauc uuagaguuau u 21 <210> 3013 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3013 aacauugaag cauugagacu u 21 <210> 3014 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3014 acauccggaa caagccauca c 21 <210> 3015 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3015 acaucugcaa caagccauca c 21 <210> 3016 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3016 uuccacauaa cuuucguucu gaa 23 <210> 3017 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3017 uuccauacaa cuuucguucu gaa 23 <210> 3018 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3018 aaucuuauau uccaggacau auu 23 <210> 3019 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3019 aaucuaacau uccaggacau auu 23 <210> 3020 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3020 acauccaaua uuccaggaca uuu 23 <210> 3021 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3021 acaucuauua uuccaggaca uuu 23 <210> 3022 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3022 agcauuuaau auuccaggac auu 23 <210> 3023 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3023 agcaucuuau auuccaggac auu 23 <210> 3024 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3024 aggcaccuaa uauuccaggu u 21 <210> 3025 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3025 aggcauccaa uauuccaggu u 21 <210> 3026 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3026 aaggcuucua auauuccagg a 21 <210> 3027 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3027 aaggcauuua auauuccagg a 21 <210> 3028 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3028 aaagguaucu aauauuccag guu 23 <210> 3029 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3029 aaaggcaccu aauauuccag guu 23 <210> 3030 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3030 aaaagccauc uaauauucca guu 23 <210> 3031 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3031 aaaaggcuuc uaauauucca guu 23 <210> 3032 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3032 uuuaauaggc aucuaauauu cuu 23 <210> 3033 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3033 uuuaaaacgc aucuaauauu cuu 23 <210> 3034 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3034 agaacuuuuu uaaaaggcau cuu 23 <210> 3035 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3035 agaacaucuu uaaaaggcau cuu 23 <210> 3036 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3036 aagaccaaaa augugaaaau cuu 23 <210> 3037 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3037 aagacgauaa augugaaaau cuu 23 <210> 3038 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3038 augggucauu gaagcauuga guu 23 <210> 3039 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3039 augggacuuu gaagcauuga guu 23 <210> 3040 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3040 aacugcgaca uugaagcauu g 21 <210> 3041 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3041 aacuggguca uugaagcauu g 21 <210> 3042 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3042 uaagucauug agacuauauu uuu 23 <210> 3043 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3043 uaaguuacug agacuauauu uuu 23 <210> 3044 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3044 agggacuuuu cagaauccug cuu 23 <210> 3045 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3045 agggagucuu cagaauccug cuu 23 <210> 3046 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3046 ugcaacucug cgcucuuggu auu 23 <210> 3047 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3047 ugcaaguuug cgcucuuggu auu 23 <210> 3048 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3048 acaaccgaca uaugcuuucc uuu 23 <210> 3049 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3049 acaacuguca uaugcuuucc uuu 23 <210> 3050 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3050 uagauuuugg guuuuaaacu u 21 <210> 3051 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3051 uagauaucgg guuuuaaacu u 21 <210> 3052 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3052 uagagcuaua caaucaguua auu 23 <210> 3053 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3053 uagaguuuua caaucaguua auu 23 <210> 3054 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3054 auucaccaga ucuuagaguu a 21 <210> 3055 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3055 auucaucuga ucuuagaguu a 21 <210> 3056 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3056 uacuuuauca gaucuuagag uuu 23 <210> 3057 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3057 uacuucacca gaucuuagag uuu 23 <210> 3058 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3058 ucaaacgaca aaauggcaau auu 23 <210> 3059 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3059 ucaaagguca aaauggcaau auu 23 <210> 3060 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3060 auaauuaaag gacaaaaugg cuu 23 <210> 3061 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3061 auaaucauag gacaaaaugg cuu 23 <210> 3062 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3062 guauguccug gaauauuaga 20 <210> 3063 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3063 aggcuagaga agaaaguuaa 20 <210> 3064 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3064 uguauaacuc uaagaucuga 20 <210> 3065 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3065 ccguaugucc uggaauauua 20 <210> 3066 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3066 caaaaaugac aacacuugaa 20 <210> 3067 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3067 uacugaaaac cuuuaaaggg 20 <210> 3068 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3068 acuacugaaa accuuuaaag 20 <210> 3069 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3069 agaagaaaag ugauucagug 20 <210> 3070 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3070 uuugggcagu auuuugugcu 20 <210> 3071 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3071 uaccaagagc gcagacuugc 20 <210> 3072 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3072 cgggcuagcu uuugaaaugg 20 <210> 3073 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3073 cuggaaacac ugaagaguua 20 <210> 3074 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3074 augucccagu gcaaaaagua 20 <210> 3075 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3075 cuggaauauu agaugccuuu 20 <210> 3076 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3076 ccuggaauau uagaugccuu 20 <210> 3077 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3077 uccuggaaua uuagaugccu 20 <210> 3078 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3078 acucuaagau cugaugaagu 20 <210> 3079 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3079 guccuggaau auuagaugcc 20 <210> 3080 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3080 uguccuggaa uauuagaugc 20 <210> 3081 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3081 uaacucuaag aucugaugaa 20 <210> 3082 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3082 gugauggcuu guuccagaug 20 <210> 3083 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3083 gucuaugcag aggauucuug 20 <210> 3084 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3084 acccugacuc ucagugcagc 20 <210> 3085 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3085 agccuacaca aaggaccuac 20 <210> 3086 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3086 accaagagcg cagacuugca 20 <210> 3087 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3087 gaaggaaccg cuggaaacac 20 <210> 3088 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3088 uucccuuuuc uucucaagcc 20 <210> 3089 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3089 ccugucacua ccacucguua 20 <210> 3090 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3090 cgcgcuuugu ccuccucgcg 20 <210> 3091 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3091 gaaacauggu uacugcucgc 20 <210> 3092 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3092 cuuuguccuc cucgcgcaau 20 <210> 3093 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3093 gcauaaagac ugaggugacc 20 <210> 3094 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3094 uuuguccucc ucgcgcaauc 20 <210> 3095 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3095 gaaaagggug auggcuuguu 20 <210> 3096 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3096 aaaaggguga uggcuuguuc 20 <210> 3097 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3097 cuacugccua ucaaaacgcc 20 <210> 3098 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3098 cucaucaaau agcagacuug 20 <210> 3099 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3099 agacaccagc ccauucuuga 20 <210> 3100 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3100 cagcccauuc uugauccuuu 20 <210> 3101 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3101 gcagaggauu cuugggauga 20 <210> 3102 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3102 cuaaaggugc ucaggaggau 20 <210> 3103 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3103 aaagcauaug ucaguuguuu 20 <210> 3104 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3104 uuaacugauu guauaacucu 20 <210> 3105 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3105 uaacugauug uauaacucua 20 <210> 3106 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3106 ugaaaacucc ccguuuaacu 20 <210> 3107 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3107 gaugccuuuu aaaaauguuc 20 <210> 3108 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3108 aaguugacua aacuugaaaa 20 <210> 3109 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3109 cacaaaggac cuacuacugc 20 <210> 3110 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3110 gauuuucaca uuuuucgucu 20 <210> 3111 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3111 ccauucuuga uccuuucuga 20 <210> 3112 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3112 gaauauuaga ugccuuuuaa 20 <210> 3113 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3113 aaggaaagca uaugucaguu 20 <210> 3114 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3114 aggaaagcau augucaguug 20 <210> 3115 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3115 ccccguuuaa cugauuaugg 20 <210> 3116 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3116 ggaaagcaua ugucaguugu 20 <210> 3117 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3117 gccauuuugu ccuuugauua 20 <210> 3118 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3118 augacaacac uugaagcaug 20 <210> 3119 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3119 cuccugcuuc uccguuuauc 20 <210> 3120 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3120 cagacuugca uccugucacu 20 <210> 3121 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3121 gagggaaaca ugguuacugc 20 <210> 3122 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3122 uggcauaaag acugagguga 20 <210> 3123 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3123 uccuagaaug uguuauugcc 20 <210> 3124 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3124 uggaaacacu gaagaguuau 20 <210> 3125 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3125 uggauuuccu aaaggugcuc 20 <210> 3126 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3126 gaggagaaga aaagugauuc 20 <210> 3127 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3127 accuacuacu gccuaucaaa 20 <210> 3128 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3128 uacuacugcc uaucaaaacg 20 <210> 3129 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3129 aaauauaguc ucaauaacuu 20 <210> 3130 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3130 aacucuaaga ucugaugaag 20 <210> 3131 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3131 aagaguuauc gccaguguga 20 <210> 3132 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3132 ccgggcuagc uuuugaaaug 20 <210> 3133 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3133 guuauaugga aaaucaccac 20 <210> 3134 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3134 aaagugauuc agugauuuca 20 <210> 3135 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3135 uauguccugg aauauuagau 20 <210> 3136 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3136 auaacucuaa gaucugauga 20 <210> 3137 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3137 cuuguuccag augcauuuua 20 <210> 3138 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3138 uauugccauu uuguccuuug 20 <210> 3139 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3139 ugauuuucac auuuuucguc 20 <210> 3140 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3140 caagagcgca gacuugcauc 20 <210> 3141 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3141 cagauagacu acugaaaacc 20 <210> 3142 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3142 uuauggaaua guucuuucuc 20 <210> 3143 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3143 caugguguuu cagaacugag 20 <210> 3144 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3144 gaagaaaagu gauucaguga 20 <210> 3145 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3145 gucccagugc aaaaaguaaa 20 <210> 3146 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3146 acugauugua uaacucuaag 20 <210> 3147 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3147 accguauguc cuggaauauu 20 <210> 3148 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3148 uccccguuua acugauuaug 20 <210> 3149 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3149 auauagucuc aauaacuuag 20 <210> 3150 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3150 ucccagugca aaaaguaaag 20 <210> 3151 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3151 augcuucaau gucccaguuu 20 <210> 3152 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3152 gaacgaaagu uauauggaau 20 <210> 3153 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3153 gauugcuuac ucagacacuu 20 <210> 3154 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3154 cuucaggccc aauauuguaa 20 <210> 3155 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3155 caaugcuuca augucccagu 20 <210> 3156 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3156 cagaacgaaa guuauaugga 20 <210> 3157 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3157 ggaaguugac uaaacuugaa 20 <210> 3158 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3158 ccaguggaua accagcuucc 20 <210> 3159 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3159 cuaagaucug augaaguaua 20 <210> 3160 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3160 cagauugcuu acucagacac 20 <210> 3161 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3161 caaugcuuca augucccagu 20 <210> 3162 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3162 caaugcuuca augucccauu 20 <210> 3163 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3163 guuuaaaacc caauaucuau 20 <210> 3164 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3164 cuucaauguc ccagugcaau 20 <210> 3165 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3165 agacagcauu ggauuuccuu 20 <210> 3166 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3166 gaaaaucacc acucuuuguu 20 <210> 3167 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3167 acagcauugg auuuccuaau 20 <210> 3168 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3168 aggauucuga aaacucccuu 20 <210> 3169 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3169 caacacuuga agcaugguuu 20 <210> 3170 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3170 cucaaugcuu caauguccca 20 <210> 3171 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3171 uuguuuaaaa cccaauaucu 20 <210> 3172 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3172 ugcuucaaug ucccagugca 20 <210> 3173 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3173 ucagacagca uuggauuucc 20 <210> 3174 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3174 uggaaaauca ccacucuuug 20 <210> 3175 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3175 agacagcauu ggauuuccua 20 <210> 3176 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3176 acaggauucu gaaaacuccc 20 <210> 3177 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3177 gacaacacuu gaagcauggu 20 <210> 3178 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3178 cuguuuaaaa cccaauaucu 20 <210> 3179 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3179 cgcuucaaug ucccagugca 20 <210> 3180 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3180 ccagacagca uuggauuucc 20 <210> 3181 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3181 cggaaaauca ccacucuuug 20 <210> 3182 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3182 ggacagcauu ggauuuccua 20 <210> 3183 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3183 gcaggauucu gaaaacuccc 20 <210> 3184 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3184 gauggcuugu uccagauguu 20 <210> 3185 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3185 uccuggaaua uuagaugcuu 20 <210> 3186 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3186 ucuaagaucu gaugaaguau 20 <210> 3187 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3187 gugauggcuu guuccagaug 20 <210> 3188 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3188 uguccuggaa uauuagaugc 20 <210> 3189 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3189 guccuggaau auuagaugcc 20 <210> 3190 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3190 acucuaagau cugaugaagu 20 <210> 3191 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3191 uccuggaaua uuagaugccu 20 <210> 3192 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3192 cccuggaaua uuagaugccu 20 <210> 3193 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3193 gcucuaagau cugaugaagu 20 <210> 3194 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3194 cguccuggaa uauuagaugc 20 <210> 3195 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3195 caacucuaag aucugaugaa 20 <210> 3196 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3196 ggaagaaaag ugauucagug 20 <210> 3197 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3197 guccuggaau auuagaugcc 20 <210> 3198 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3198 uccuggaaua uuagaugccu 20 <210> 3199 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3199 acucuaagau cugaugaagu 20 <210> 3200 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3200 agacagcauu ggauuuccua 20 <210> 3201 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3201 guccaggaau auuagaugcc 20 <210> 3202 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3202 gugcuggaau auuagaugcc 20 <210> 3203 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3203 uccucgaaua uuagaugccu 20 <210> 3204 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3204 ucguggaaua uuagaugccu 20 <210> 3205 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3205 acacuaagau cugaugaagu 20 <210> 3206 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3206 agucuaagau cugaugaagu 20 <210> 3207 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3207 agucagcauu ggauuuccua 20 <210> 3208 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3208 acacagcauu ggauuuccua 20 <210> 3209 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3209 guccuggaau auuagaugcc 20 <210> 3210 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3210 guccuggaau auuagaugcc 20 <210> 3211 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3211 guccuggaau auuagaugcc 20 <210> 3212 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3212 auguccugga auauuagaug 20 <210> 3213 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3213 uauaacucua agaucugaug 20 <210> 3214 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3214 uaagaucuga ugaaguauau 20 <210> 3215 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3215 ggugucucaa ugcuucaaug 20 <210> 3216 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3216 gugucucaau gcuucaaugu 20 <210> 3217 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3217 ucucaaugcu ucaauguccc 20 <210> 3218 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3218 aaugcuucaa ugucccagug 20 <210> 3219 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3219 augcuucaau gucccagugc 20 <210> 3220 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3220 uccuggaaua uuagaugccu 20 <210> 3221 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3221 acucuaagau cugaugaagu 20 <210> 3222 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3222 guccuggaau auuagaugcc 20 <210> 3223 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3223 uguccuggaa uauuagaugc 20 <210> 3224 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3224 uaacucuaag aucugaugaa 20 <210> 3225 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3225 uaacucuaag aucugaugaa 20 <210> 3226 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3226 ugauggcuug uuccagaugc 20 <210> 3227 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3227 gauggcuugu uccagaugca 20 <210> 3228 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3228 cucagacagc auuggauuuc 20 <210> 3229 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3229 ugccauuuug uccuuugauu 20 <210> 3230 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3230 ccauuuuguc cuuugauuau 20 <210> 3231 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3231 ugauggcuug uuccagaugc 20 <210> 3232 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3232 gauggcuugu uccagaugca 20 <210> 3233 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3233 cucagacagc auuggauuuc 20 <210> 3234 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3234 ugccauuuug uccuuugauu 20 <210> 3235 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3235 ccauuuuguc cuuugauuau 20 <210> 3236 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3236 gauuuucaca uuuuucgucu 20 <210> 3237 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3237 gauuuucaca uuuuucgucu 20 <210> 3238 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3238 gaauauuaga ugccuuuuaa 20 <210> 3239 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3239 aggaaagcau augucaguug 20 <210> 3240 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3240 gccauuuugu ccuuugauua 20 <210> 3241 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3241 gauuuucaca uuuuucgucu 20 <210> 3242 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3242 augcuucaau gucccaguuu 20 <210> 3243 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3243 aaauauaguc ucaauaacuu 20 <210> 3244 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3244 uaccaagagc gcagacuugc 20 <210> 3245 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3245 gaugccuuuu aaaaauguuc 20 <210> 3246 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3246 auguccugga auauuagaug 20 <210> 3247 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3247 uuuucacauu uuucgucuuu 20 <210> 3248 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3248 auauuagaug ccuuuuaaau 20 <210> 3249 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3249 gaaagcauau gucaguuguu 20 <210> 3250 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3250 cauuuugucc uuugauuauu 20 <210> 3251 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3251 auauagucuc aauaacuuau 20 <210> 3252 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3252 ccaagagcgc agacuugcau 20 <210> 3253 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3253 ugccuuuuaa aaauguucuu 20 <210> 3254 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3254 guccuggaau auuagauguu 20 <210> 3255 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3255 gcucuaagau cugaugaagu 20 <210> 3256 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3256 ccuaagaucu gaugaaguau 20 <210> 3257 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3257 ccuaagaucu gaugaaguau 20 <210> 3258 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3258 agaagaaaag ugauucagug 20 <210> 3259 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3259 acucuaagau cugaugaauu 20 <210> 3260 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3260 aagaaaagug auucagugau 20 <210> 3261 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3261 ccuggaauau uagaugccuu 20 <210> 3262 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3262 uagcagacuu guuccgacuu 20 <210> 3263 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3263 ccguuuaacu gauuauggau 20 <210> 3264 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3264 gacaacacuu gaagcauguu 20 <210> 3265 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3265 uugccauuuu guccuuugau 20 <210> 3266 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3266 uaacucuaag aucugaugau 20 <210> 3267 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3267 gucucaaugc uucaauguuu 20 <210> 3268 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3268 aauagcagac uuguuccgac 20 <210> 3269 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3269 ccccguuuaa cugauuaugg 20 <210> 3270 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3270 augacaacac uugaagcaug 20 <210> 3271 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3271 uauugccauu uuguccuuug 20 <210> 3272 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3272 uauaacucua agaucugaug 20 <210> 3273 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3273 gugucucaau gcuucaaugu 20 <210> 3274 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3274 gugauggcuu guuccggaug 20 <210> 3275 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3275 gugauggcuu guugcagaug 20 <210> 3276 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3276 cagaacgaaa guuaugugga 20 <210> 3277 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3277 cagaacgaaa guuguaugga 20 <210> 3278 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3278 uauguccugg aauauaagau 20 <210> 3279 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3279 uauguccugg aauguuagau 20 <210> 3280 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3280 auguccugga auauuggaug 20 <210> 3281 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3281 auguccugga auaauagaug 20 <210> 3282 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3282 uguccuggaa uauuaaaugc 20 <210> 3283 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3283 uguccuggaa uauaagaugc 20 <210> 3284 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3284 ccuggaauau uaggugccuu 20 <210> 3285 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3285 ccuggaauau uggaugccuu 20 <210> 3286 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3286 uccuggaaua uuagaagccu 20 <210> 3287 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3287 uccuggaaua uuaaaugccu 20 <210> 3288 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3288 ccuggaauau uagauaccuu 20 <210> 3289 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3289 cuggaauauu agauggcuuu 20 <210> 3290 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3290 cuggaauauu agaagccuuu 20 <210> 3291 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3291 gaauauuaga ugccuauuaa 20 <210> 3292 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3292 gaauauuaga ugcguuuuaa 20 <210> 3293 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3293 gaugccuuuu aaaaaaguuc 20 <210> 3294 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3294 gaugccuuuu aaagauguuc 20 <210> 3295 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3295 gauuuucaca uuuuuggucu 20 <210> 3296 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3296 gauuuucaca uuuaucgucu 20 <210> 3297 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3297 cucaaugcuu caaugaccca 20 <210> 3298 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3298 cucaaugcuu caaaguccca 20 <210> 3299 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3299 caaugcuuca augucgcagu 20 <210> 3300 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3300 caaugcuuca augacccagu 20 <210> 3301 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3301 aaauauaguc ucaaugacuu 20 <210> 3302 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3302 aaauauaguc ucaguaacuu 20 <210> 3303 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3303 gcaggauucu gaaaaguccc 20 <210> 3304 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3304 gcaggauucu gaagacuccc 20 <210> 3305 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3305 uaccaagagc gcagaguugc 20 <210> 3306 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3306 uaccaagagc gcaaacuugc 20 <210> 3307 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3307 aggaaagcau augucgguug 20 <210> 3308 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3308 aggaaagcau augacaguug 20 <210> 3309 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3309 guuuaaaacc caaaaucuau 20 <210> 3310 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3310 guuuaaaacc cgauaucuau 20 <210> 3311 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3311 uuaacugauu guauagcucu 20 <210> 3312 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3312 uuaacugauu guaaaacucu 20 <210> 3313 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3313 uaacucuaag aucuggugaa 20 <210> 3314 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3314 uaacucuaag aucagaugaa 20 <210> 3315 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3315 acucuaagau cugauaaagu 20 <210> 3316 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3316 acucuaagau cuggugaagu 20 <210> 3317 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3317 uauugccauu uugucguuug 20 <210> 3318 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3318 uauugccauu uugaccuuug 20 <210> 3319 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3319 gccauuuugu ccuuuaauua 20 <210> 3320 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, inverted abasic, phosphorothioate linked ribonucleotides <400> 3320 gccauuuugu ccuaugauua 20 <210> 3321 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3321 aucuaauauu ccaggacaua cuu 23 <210> 3322 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3322 uuuaacuuuc uucucuagcc uuu 23 <210> 3323 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3323 aucagaucuu agaguuauac auu 23 <210> 3324 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3324 auaauauucc aggacauacg guu 23 <210> 3325 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3325 auucaagugu ugucauuuuu guu 23 <210> 3326 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3326 acccuuuaaa gguuuucagu auu 23 <210> 3327 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3327 acuuuaaagg uuuucaguag uuu 23 <210> 3328 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(20) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3328 ucacugaauc acuuuucuuc uuu 23 <210> 3329 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3329 aagcacaaaa uacugcccaa auu 23 <210> 3330 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3330 ugcaagucug cgcucuuggu auu 23 <210> 3331 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3331 accauuucaa aagcuagccc guu 23 <210> 3332 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3332 auaacucuuc aguguuucca guu 23 <210> 3333 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3333 uuacuuuuug cacugggaca uuu 23 <210> 3334 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3334 aaaaggcauc uaauauucca guu 23 <210> 3335 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3335 aaaggcaucu aauauuccag guu 23 <210> 3336 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3336 aaggcaucua auauuccagg auu 23 <210> 3337 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3337 uacuucauca gaucuuagag uuu 23 <210> 3338 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3338 aggcaucuaa uauuccagga cuu 23 <210> 3339 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3339 agcaucuaau auuccaggac auu 23 <210> 3340 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3340 auucaucaga ucuuagaguu auu 23 <210> 3341 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3341 acaucuggaa caagccauca cuu 23 <210> 3342 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3342 acaagaaucc ucugcauaga cuu 23 <210> 3343 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3343 agcugcacug agagucaggg uuu 23 <210> 3344 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3344 aguagguccu uuguguaggc uuu 23 <210> 3345 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3345 augcaagucu gcgcucuugg uuu 23 <210> 3346 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3346 aguguuucca gcgguuccuu cuu 23 <210> 3347 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3347 aggcuugaga agaaaaggga auu 23 <210> 3348 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3348 auaacgagug guagugacag guu 23 <210> 3349 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3349 acgcgaggag gacaaagcgc guu 23 <210> 3350 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3350 agcgagcagu aaccauguuu cuu 23 <210> 3351 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3351 aauugcgcga ggaggacaaa guu 23 <210> 3352 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3352 aggucaccuc agucuuuaug cuu 23 <210> 3353 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3353 agauugcgcg aggaggacaa auu 23 <210> 3354 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3354 aaacaagcca ucacccuuuu cuu 23 <210> 3355 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3355 agaacaagcc aucacccuuu uuu 23 <210> 3356 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3356 aggcguuuug auaggcagua guu 23 <210> 3357 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3357 acaagucugc uauuugauga guu 23 <210> 3358 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3358 aucaagaaug ggcugguguc uuu 23 <210> 3359 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3359 aaaaggauca agaaugggcu guu 23 <210> 3360 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3360 aucaucccaa gaauccucug cuu 23 <210> 3361 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3361 aauccuccug agcaccuuua guu 23 <210> 3362 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3362 uaaacaacug acauaugcuu uuu 23 <210> 3363 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3363 uagaguuaua caaucaguua auu 23 <210> 3364 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3364 uuagaguuau acaaucaguu auu 23 <210> 3365 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3365 aaguuaaacg gggaguuuuc auu 23 <210> 3366 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3366 agaacauuuu uaaaaggcau cuu 23 <210> 3367 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3367 uuuuucaagu uuagucaacu uuu 23 <210> 3368 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3368 agcaguagua gguccuuugu guu 23 <210> 3369 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3369 aagacgaaaa augugaaaau cuu 23 <210> 3370 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3370 aucagaaagg aucaagaaug guu 23 <210> 3371 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3371 uuuaaaaggc aucuaauauu cuu 23 <210> 3372 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3372 aaacugacau augcuuuccu uuu 23 <210> 3373 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3373 acaacugaca uaugcuuucc uuu 23 <210> 3374 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3374 uccauaauca guuaaacggg guu 23 <210> 3375 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3375 aacaacugac auaugcuuuc cuu 23 <210> 3376 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3376 auaaucaaag gacaaaaugg cuu 23 <210> 3377 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3377 acaugcuuca aguguuguca uuu 23 <210> 3378 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3378 agauaaacgg agaagcagga guu 23 <210> 3379 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3379 uagugacagg augcaagucu guu 23 <210> 3380 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3380 agcaguaacc auguuucccu cuu 23 <210> 3381 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3381 aucaccucag ucuuuaugcc auu 23 <210> 3382 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3382 aggcaauaac acauucuagg auu 23 <210> 3383 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3383 aauaacucuu caguguuucc auu 23 <210> 3384 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3384 ugagcaccuu uaggaaaucc auu 23 <210> 3385 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3385 ugaaucacuu uucuucuccu cuu 23 <210> 3386 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3386 uuuugauagg caguaguagg uuu 23 <210> 3387 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3387 acguuuugau aggcaguagu auu 23 <210> 3388 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3388 uaaguuauug agacuauauu uuu 23 <210> 3389 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3389 acuucaucag aucuuagagu uuu 23 <210> 3390 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3390 aucacacugg cgauaacucu uuu 23 <210> 3391 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3391 acauuucaaa agcuagcccg guu 23 <210> 3392 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3392 aguggugauu uuccauauaa cuu 23 <210> 3393 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3393 augaaaucac ugaaucacuu uuu 23 <210> 3394 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3394 aaucuaauau uccaggacau auu 23 <210> 3395 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3395 uucaucagau cuuagaguua uuu 23 <210> 3396 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3396 uuaaaaugca ucuggaacaa guu 23 <210> 3397 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3397 ucaaaggaca aaauggcaau auu 23 <210> 3398 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3398 agacgaaaaa ugugaaaauc auu 23 <210> 3399 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3399 agaugcaagu cugcgcucuu guu 23 <210> 3400 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3400 agguuuucag uagucuaucu guu 23 <210> 3401 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3401 agagaaagaa cuauuccaua auu 23 <210> 3402 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3402 ucucaguucu gaaacaccau guu 23 <210> 3403 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3403 aucacugaau cacuuuucuu cuu 23 <210> 3404 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3404 auuuacuuuu ugcacuggga cuu 23 <210> 3405 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3405 ucuuagaguu auacaaucag uuu 23 <210> 3406 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3406 uaauauucca ggacauacgg uuu 23 <210> 3407 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3407 acauaaucag uuaaacgggg auu 23 <210> 3408 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3408 acuaaguuau ugagacuaua uuu 23 <210> 3409 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3409 ucuuuacuuu uugcacuggg auu 23 <210> 3410 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3410 aacugggaca uugaagcauu u 21 <210> 3411 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3411 uuccauauaa cuuucguucu u 21 <210> 3412 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3412 agugucugag uaagcaaucu u 21 <210> 3413 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3413 auuacaauau ugggccugaa guu 23 <210> 3414 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3414 aacugggaca uugaagcauu guu 23 <210> 3415 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3415 uuccauauaa cuuucguucu guu 23 <210> 3416 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3416 uuucaaguuu agucaacuuc cuu 23 <210> 3417 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3417 aggaagcugg uuauccacug guu 23 <210> 3418 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3418 auauacuuca ucagaucuua guu 23 <210> 3419 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3419 agugucugag uaagcaaucu guu 23 <210> 3420 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3420 auuacaauau ugggccugaa gug 23 <210> 3421 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3421 aacugggaca uugaagcauu gug 23 <210> 3422 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3422 uuccauauaa cuuucguucu gug 23 <210> 3423 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3423 uuucaaguuu agucaacuuc cug 23 <210> 3424 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3424 aggaagcugg uuauccacug gug 23 <210> 3425 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3425 auauacuuca ucagaucuua gug 23 <210> 3426 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3426 agugucugag uaagcaaucu gug 23 <210> 3427 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3427 aacugggaca uugaagcauu gag 23 <210> 3428 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3428 aacugggaca uugaagcauu guu 23 <210> 3429 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3429 aacugggaca uugaagcauu guu 23 <210> 3430 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3430 aacugggaca uugaagcauu guu 23 <210> 3431 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3431 aacugggaca uugaagcauu guu 23 <210> 3432 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3432 aacugggaca uugaagcauu guu 23 <210> 3433 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3433 auuacaauau ugggccugaa g 21 <210> 3434 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3434 aacugggaca uugaagcauu g 21 <210> 3435 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3435 uuccauauaa cuuucguucu g 21 <210> 3436 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3436 uuucaaguuu agucaacuuc c 21 <210> 3437 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3437 aggaagcugg uuauccacug g 21 <210> 3438 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3438 auauacuuca ucagaucuua g 21 <210> 3439 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3439 agugucugag uaagcaaucu g 21 <210> 3440 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3440 augggacauu gaagcauugu u 21 <210> 3441 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3441 uagauauugg guuuuaaacu u 21 <210> 3442 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3442 uugcacuggg acauugaagu u 21 <210> 3443 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3443 aggaaaucca augcugucuu u 21 <210> 3444 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3444 acaaagagug gugauuuucu u 21 <210> 3445 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3445 uuaggaaauc caaugcuguu u 21 <210> 3446 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3446 agggaguuuu cagaauccuu u 21 <210> 3447 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3447 aaccaugcuu caaguguugu u 21 <210> 3448 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3448 augggacauu gaagcauuga guu 23 <210> 3449 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3449 uagauauugg guuuuaaaca auu 23 <210> 3450 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3450 uugcacuggg acauugaagc auu 23 <210> 3451 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3451 aggaaaucca augcugucug auu 23 <210> 3452 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3452 acaaagagug gugauuuucc auu 23 <210> 3453 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3453 uuaggaaauc caaugcuguc uuu 23 <210> 3454 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3454 agggaguuuu cagaauccug uuu 23 <210> 3455 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3455 aaccaugcuu caaguguugu cuu 23 <210> 3456 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3456 augggacauu gaagcauuga g 21 <210> 3457 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3457 uagauauugg guuuuaaaca a 21 <210> 3458 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3458 uugcacuggg acauugaagc a 21 <210> 3459 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3459 aggaaaucca augcugucug a 21 <210> 3460 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3460 acaaagagug gugauuuucc a 21 <210> 3461 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3461 uuaggaaauc caaugcuguc u 21 <210> 3462 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3462 agggaguuuu cagaauccug u 21 <210> 3463 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3463 aaccaugcuu caaguguugu c 21 <210> 3464 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3464 uagauauugg guuuuaaaca guu 23 <210> 3465 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3465 uugcacuggg acauugaagc guu 23 <210> 3466 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3466 aggaaaucca augcugucug guu 23 <210> 3467 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3467 acaaagagug gugauuuucc guu 23 <210> 3468 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3468 uuaggaaauc caaugcuguc cuu 23 <210> 3469 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3469 agggaguuuu cagaauccug cuu 23 <210> 3470 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3470 acaucuggaa caagccaucu u 21 <210> 3471 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3471 agcaucuaau auuccaggau u 21 <210> 3472 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3472 aggcaucuaa uauuccaggu u 21 <210> 3473 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3473 uacuucauca gaucuuagau u 21 <210> 3474 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3474 aaggcaucua auauuccagu u 21 <210> 3475 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3475 acaucuggaa caagccauca cuu 23 <210> 3476 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3476 agcaucuaau auuccaggac auu 23 <210> 3477 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3477 aggcaucuaa uauuccagga cuu 23 <210> 3478 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3478 uacuucauca gaucuuagag uuu 23 <210> 3479 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3479 aaggcaucua auauuccagg auu 23 <210> 3480 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3480 acaucuggaa caagccauca c 21 <210> 3481 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3481 agcaucuaau auuccaggac a 21 <210> 3482 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3482 aggcaucuaa uauuccagga c 21 <210> 3483 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3483 uacuucauca gaucuuagag u 21 <210> 3484 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3484 aaggcaucua auauuccagg a 21 <210> 3485 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3485 aaggcaucua auauuccagg guu 23 <210> 3486 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3486 uacuucauca gaucuuagag cuu 23 <210> 3487 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3487 agcaucuaau auuccaggac guu 23 <210> 3488 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3488 auucaucaga ucuuagaguu guu 23 <210> 3489 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3489 ucacugaauc acuuuucuuc cuu 23 <210> 3490 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3490 aggcaucuaa uauuccugga cuu 23 <210> 3491 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3491 aggcaucuaa uauuccagca cuu 23 <210> 3492 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3492 aaggcaucua auauucgagg auu 23 <210> 3493 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3493 aaggcaucua auauuccacg auu 23 <210> 3494 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3494 uacuucauca gaucuuagug uuu 23 <210> 3495 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3495 uacuucauca gaucuuagac uuu 23 <210> 3496 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3496 uuaggaaauc caaugcugac uuu 23 <210> 3497 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3497 uuaggaaauc caaugcugug uuu 23 <210> 3498 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3498 aggcaucuaa uauuccagga cuu 23 <210> 3499 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3499 aggcaucuaa uauuccagga cuu 23 <210> 3500 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3500 aggcaucuaa uauuccagga cuu 23 <210> 3501 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3501 acaucuaaua uuccaggaca uuu 23 <210> 3502 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3502 ucaucagauc uuagaguuau auu 23 <210> 3503 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3503 aauauacuuc aucagaucuu auu 23 <210> 3504 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3504 acauugaagc auugagacac cuu 23 <210> 3505 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3505 aacauugaag cauugagaca cuu 23 <210> 3506 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3506 ugggacauug aagcauugag auu 23 <210> 3507 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3507 acacugggac auugaagcau uuu 23 <210> 3508 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3508 ugcacuggga cauugaagca uuu 23 <210> 3509 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3509 auucaucaga ucuuagaguu auu 23 <210> 3510 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3510 aaggcaucua auauuccagg auu 23 <210> 3511 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3511 uacuucauca gaucuuagag uuu 23 <210> 3512 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3512 aggcaucuaa uauuccagga cuu 23 <210> 3513 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3513 agcaucuaau auuccaggac auu 23 <210> 3514 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3514 auucaucaga ucuuagaguu auu 23 <210> 3515 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3515 aaggcaucua auauuccagg auu 23 <210> 3516 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3516 uacuucauca gaucuuagag uuu 23 <210> 3517 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3517 agcaucuaau auuccaggac auu 23 <210> 3518 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3518 auucaucaga ucuuagaguu auu 23 <210> 3519 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3519 aaggcaucua auauuccagg auu 23 <210> 3520 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3520 uacuucauca gaucuuagag uuu 23 <210> 3521 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3521 agcaucuaau auuccaggac auu 23 <210> 3522 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3522 auucaucaga ucuuagaguu auu 23 <210> 3523 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3523 ugcaucugga acaagccauc auu 23 <210> 3524 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3524 augcaucugg aacaagccau cuu 23 <210> 3525 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3525 agaaauccaa ugcugucuga guu 23 <210> 3526 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3526 uaaucaaagg acaaaauggc auu 23 <210> 3527 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3527 uauaaucaaa ggacaaaaug guu 23 <210> 3528 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3528 ugcaucugga acaagccauc auu 23 <210> 3529 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3529 augcaucugg aacaagccau cuu 23 <210> 3530 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3530 agaaauccaa ugcugucuga guu 23 <210> 3531 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3531 uaaucaaagg acaaaauggc auu 23 <210> 3532 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3532 uauaaucaaa ggacaaaaug guu 23 <210> 3533 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3533 ugcaucugga acaagccauc auu 23 <210> 3534 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3534 augcaucugg aacaagccau cuu 23 <210> 3535 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3535 agaaauccaa ugcugucuga guu 23 <210> 3536 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3536 uaaucaaagg acaaaauggc auu 23 <210> 3537 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3537 uauaaucaaa ggacaaaaug guu 23 <210> 3538 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3538 aagacgaaaa augugaaaau cuu 23 <210> 3539 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3539 uuuaaaaggc aucuaauauu cuu 23 <210> 3540 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3540 acaacugaca uaugcuuucc uuu 23 <210> 3541 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3541 auaaucaaag gacaaaaugg cuu 23 <210> 3542 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3542 aacugggaca uugaagcauu g 21 <210> 3543 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3543 aacugggaca uugaagcauu u 21 <210> 3544 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3544 aacugggaca uugaagcauu gag 23 <210> 3545 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3545 aacugggaca uugaagcauu g 21 <210> 3546 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3546 aacugggaca uugaagcauu u 21 <210> 3547 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3547 aacugggaca uugaagcauu gag 23 <210> 3548 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3548 aagacgaaaa augugaaaau c 21 <210> 3549 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3549 uuuaaaaggc aucuaauauu c 21 <210> 3550 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3550 acaacugaca uaugcuuucc u 21 <210> 3551 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3551 auaaucaaag gacaaaaugg c 21 <210> 3552 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3552 uaaguuauug agacuauauu u 21 <210> 3553 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3553 ugcaagucug cgcucuuggu a 21 <210> 3554 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3554 agaacauuuu uaaaaggcau c 21 <210> 3555 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3555 acaucuaaua uuccaggaca u 21 <210> 3556 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3556 uaaguuauug agacuauauu uuu 23 <210> 3557 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3557 ugcaagucug cgcucuuggu auu 23 <210> 3558 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3558 agaacauuuu uaaaaggcau cuu 23 <210> 3559 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3559 acaucuaaua uuccaggaca uuu 23 <210> 3560 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3560 aagacgaaaa augugaaaau u 21 <210> 3561 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3561 uuuaaaaggc aucuaauauu u 21 <210> 3562 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3562 acaacugaca uaugcuuucu u 21 <210> 3563 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3563 auaaucaaag gacaaaaugu u 21 <210> 3564 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3564 ugcaagucug cgcucuuggu u 21 <210> 3565 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3565 agaacauuuu uaaaaggcau u 21 <210> 3566 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3566 acaucuaaua uuccaggacu u 21 <210> 3567 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3567 uacuucauca gaucuuagag cuu 23 <210> 3568 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3568 uacuucauca gaucuuagag cuu 23 <210> 3569 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3569 uacuucauca gaucuuagag cuu 23 <210> 3570 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3570 uacuucauca gaucuuaggu u 21 <210> 3571 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3571 uacuucauca gaucuuaggu u 21 <210> 3572 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3572 uagauauugg guuuuaaaca acu 23 <210> 3573 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3573 uuccauauaa cuuucguucu gaa 23 <210> 3574 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3574 auauacuuca ucagaucuua gag 23 <210> 3575 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3575 acaaagagug gugauuuucc aua 23 <210> 3576 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3576 auucaucaga ucuuagaguu a 21 <210> 3577 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3577 ucacugaauc acuuuucuuc u 21 <210> 3578 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3578 aagacgaaaa augugaaaau cac 23 <210> 3579 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3579 auucaucaga ucuuagaguu aua 23 <210> 3580 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3580 ucacugaauc acuuuucuuc ucc 23 <210> 3581 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3581 ucacugaauc acuuuucuuc uuu 23 <210> 3582 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3582 auucaucaga ucuuagaguu u 21 <210> 3583 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3583 ucacugaauc acuuuucuuu u 21 <210> 3584 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3584 ugcaagucug cgcucuuggu aga 23 <210> 3585 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3585 agucggaaca agucugcuau u 21 <210> 3586 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3586 uccauaauca guuaaacggg g 21 <210> 3587 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3587 acaugcuuca aguguuguca u 21 <210> 3588 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3588 ucaaaggaca aaauggcaau a 21 <210> 3589 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3589 ucaucagauc uuagaguuau a 21 <210> 3590 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3590 aacauugaag cauugagaca c 21 <210> 3591 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3591 uccauaauca guuaaacggu u 21 <210> 3592 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3592 acaugcuuca aguguugucu u 21 <210> 3593 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3593 ucaaaggaca aaauggcaau u 21 <210> 3594 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3594 ucaucagauc uuagaguuau u 21 <210> 3595 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3595 aacauugaag cauugagacu u 21 <210> 3596 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3596 agucggaaca agucugcuau uuu 23 <210> 3597 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3597 uccauaauca guuaaacggg guu 23 <210> 3598 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3598 acaugcuuca aguguuguca uuu 23 <210> 3599 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3599 ucaaaggaca aaauggcaau auu 23 <210> 3600 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3600 ucaucagauc uuagaguuau auu 23 <210> 3601 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3601 aacauugaag cauugagaca cuu 23 <210> 3602 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3602 agucggaaca agucugcuau uuu 23 <210> 3603 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3603 uccauaauca guuaaacggg guu 23 <210> 3604 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3604 acaugcuuca aguguuguca uuu 23 <210> 3605 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3605 ucaaaggaca aaauggcaau auu 23 <210> 3606 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3606 ucaucagauc uuagaguuau auu 23 <210> 3607 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3607 aacauugaag cauugagaca cuu 23 <210> 3608 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3608 acauccggaa caagccauca c 21 <210> 3609 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3609 acaucugcaa caagccauca c 21 <210> 3610 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3610 uuccacauaa cuuucguucu gaa 23 <210> 3611 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3611 uuccauacaa cuuucguucu gaa 23 <210> 3612 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3612 aaucuuauau uccaggacau auu 23 <210> 3613 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3613 aaucuaacau uccaggacau auu 23 <210> 3614 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3614 acauccaaua uuccaggaca uuu 23 <210> 3615 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3615 acaucuauua uuccaggaca uuu 23 <210> 3616 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3616 agcauuuaau auuccaggac auu 23 <210> 3617 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3617 agcaucuuau auuccaggac auu 23 <210> 3618 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3618 aggcaccuaa uauuccaggu u 21 <210> 3619 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3619 aggcauccaa uauuccaggu u 21 <210> 3620 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3620 aaggcuucua auauuccagg a 21 <210> 3621 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3621 aaggcauuua auauuccagg a 21 <210> 3622 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3622 aaagguaucu aauauuccag guu 23 <210> 3623 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3623 aaaggcaccu aauauuccag guu 23 <210> 3624 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3624 aaaagccauc uaauauucca guu 23 <210> 3625 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3625 aaaaggcuuc uaauauucca guu 23 <210> 3626 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3626 uuuaauaggc aucuaauauu cuu 23 <210> 3627 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3627 uuuaaaacgc aucuaauauu cuu 23 <210> 3628 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3628 agaacuuuuu uaaaaggcau cuu 23 <210> 3629 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3629 agaacaucuu uaaaaggcau cuu 23 <210> 3630 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3630 aagaccaaaa augugaaaau cuu 23 <210> 3631 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3631 aagacgauaa augugaaaau cuu 23 <210> 3632 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3632 augggucauu gaagcauuga guu 23 <210> 3633 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3633 augggacuuu gaagcauuga guu 23 <210> 3634 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3634 aacugcgaca uugaagcauu g 21 <210> 3635 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3635 aacuggguca uugaagcauu g 21 <210> 3636 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3636 uaagucauug agacuauauu uuu 23 <210> 3637 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3637 uaaguuacug agacuauauu uuu 23 <210> 3638 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3638 agggacuuuu cagaauccug cuu 23 <210> 3639 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3639 agggagucuu cagaauccug cuu 23 <210> 3640 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3640 ugcaacucug cgcucuuggu auu 23 <210> 3641 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3641 ugcaaguuug cgcucuuggu auu 23 <210> 3642 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3642 acaaccgaca uaugcuuucc uuu 23 <210> 3643 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3643 acaacuguca uaugcuuucc uuu 23 <210> 3644 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3644 uagauuuugg guuuuaaacu u 21 <210> 3645 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3645 uagauaucgg guuuuaaacu u 21 <210> 3646 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3646 uagagcuaua caaucaguua auu 23 <210> 3647 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3647 uagaguuuua caaucaguua auu 23 <210> 3648 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3648 auucaccaga ucuuagaguu a 21 <210> 3649 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(21) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3649 auucaucuga ucuuagaguu a 21 <210> 3650 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3650 uacuuuauca gaucuuagag uuu 23 <210> 3651 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3651 uacuucacca gaucuuagag uuu 23 <210> 3652 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3652 ucaaacgaca aaauggcaau auu 23 <210> 3653 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3653 ucaaagguca aaauggcaau auu 23 <210> 3654 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3654 auaauuaaag gacaaaaugg cuu 23 <210> 3655 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <220> <221> misc_feature <222> (1)..(23) <223> combination of 2'-fluoro, 2'-O-methyl, phosphorothioate linked ribonucleotides <400> 3655 auaaucauag gacaaaaugg cuu 23 <210> 3656 <211> 15 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3656 caucuaauau uccag 15 <210> 3657 <211> 15 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3657 ugggacauug aagca 15 <210> 3658 <211> 15 <212> RNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3658 aucagaucuu agagu 15 <210> 3659 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3659 acctggaata 10 <210> 3660 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3660 ttagatgcct 10 <210> 3661 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3661 aaggcatcta 10 <210> 3662 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3662 atattccagg 10 <210> 3663 <211> 11 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3663 atgtcctgga a 11 <210> 3664 <211> 11 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3664 tattagatgc t 11 <210> 3665 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3665 gcatctaata 10 <210> 3666 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3666 ttccaggaca 10 <210> 3667 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3667 cctggaatat 10 <210> 3668 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3668 tagatgcctt 10 <210> 3669 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3669 aggcatctaa 10 <210> 3670 <211> 10 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3670 tattccagga 10 <210> 3671 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3671 ttcaggatgc gatgtctatg c 21 <210> 3672 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3672 tgcccaaaga gtggtgattt 20 <210> 3673 <211> 9 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3673 agccgctgg 9 <210> 3674 <211> 15 <212> DNA <213> Artificial Sequence <220> <223> synthetic polynucleotide <400> 3674 aaacactgaa gagtt 15 <210> 3675 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> synthetic polypeptide <400> 3675 Ser Pro Leu Phe Gly Gln Tyr Phe Val Leu Glu Asn Pro Gly Thr Ile 1 5 10 15 Lys <210> 3676 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> synthetic polypeptide <400> 3676 Leu Ile Ser Trp Tyr Asp Asn Glu Phe Gly Tyr Ser Asn Arg 1 5 10

Claims (97)

  1. 센스 가닥 및 안티센스 가닥을 포함하는 RNAi 작제물로서, 안티센스 가닥은 mARC1 mRNA 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함하고, 상기 영역은 표 1 또는 2에 열거된 안티센스 서열로부터의 적어도 15개의 연속 뉴클레오티드를 포함하는, RNAi 작제물.
  2. 제1항에 있어서, 센스 가닥은 안티센스 가닥의 서열에 충분히 상보적인 서열을 포함하여 약 15 내지 약 30개 염기쌍 길이의 이중체 영역을 형성하는, RNAi 작제물.
  3. 제2항에 있어서, 이중체 영역은 약 17 내지 약 24개 염기쌍 길이인, RNAi 작제물.
  4. 제2항에 있어서, 이중체 영역은 약 19 내지 약 21개 염기쌍 길이인, RNAi 작제물.
  5. 제1항 내지 제4항 중 어느 한 항에 있어서, 센스 가닥 및 안티센스 가닥은 각각 독립적으로 약 19 내지 약 30개 뉴클레오티드 길이인, RNAi 작제물.
  6. 제5항에 있어서, 센스 가닥 및 안티센스 가닥은 각각 독립적으로 약 19 내지 약 23개 뉴클레오티드 길이인, RNAi 작제물.
  7. 제1항 내지 제6항 중 어느 한 항에 있어서, RNAi 작제물은 하나 또는 두 개의 평활 말단을 포함하는, RNAi 작제물.
  8. 제1항 내지 제6항 중 어느 한 항에 있어서, RNAi 작제물은 1 내지 4개의 짝없는 뉴클레오티드의 하나 또는 두 개의 뉴클레오티드 오버행을 포함하는, RNAi 작제물.
  9. 제8항에 있어서, 뉴클레오티드 오버행은 2개의 짝없는 뉴클레오티드를 갖는, RNAi 작제물.
  10. 제8항 또는 제9항에 있어서, RNAi 작제물은 센스 가닥의 3' 말단, 안티센스 가닥의 3' 말단, 또는 센스 가닥 및 안티센스 가닥 둘 다의 3' 말단에 뉴클레오티드 오버행을 포함하는, RNAi 작제물.
  11. 제1항 내지 제10항 중 어느 한 항에 있어서, RNAi 작제물은 적어도 하나의 변형된 뉴클레오티드를 포함하는, RNAi 작제물.
  12. 제11항에 있어서, 변형된 뉴클레오티드는 2'-변형된 뉴클레오티드인, RNAi 작제물.
  13. 제11항에 있어서, 변형된 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, 이환식 핵산(BNA), 데옥시리보뉴클레오티드, 또는 이들의 조합인, RNAi 작제물.
  14. 제11항에 있어서, 센스 및 안티센스 가닥의 모든 뉴클레오티드는 변형된 뉴클레오티드인, RNAi 작제물.
  15. 제14항에 있어서, 변형된 뉴클레오티드는 2'-O-메틸 변형된 뉴클레오티드, 2'-플루오로 변형된 뉴클레오티드, 또는 이들의 조합인, RNAi 작제물.
  16. 제1항 내지 제15항 중 어느 한 항에 있어서, 센스 가닥은 이의 3' 말단, 이의 5' 말단, 또는 이의 3' 및 5' 말단 둘 다에서 말단 뉴클레오티드로서 무염기 뉴클레오티드를 포함하는, RNAi 작제물.
  17. 제16항에 있어서, 무염기 뉴클레오티드는 3'-3' 뉴클레오티드간 연결 또는 5'-5' 뉴클레오티드간 연결을 통해 인접 뉴클레오티드에 연결되는, RNAi 작제물.
  18. 제1항 내지 제17항 중 어느 한 항에 있어서, 센스 가닥, 안티센스 가닥, 또는 센스 및 안티센스 가닥 둘 다는 1개 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물.
  19. 제18항에 있어서, 안티센스 가닥은 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물.
  20. 제18항 또는 제19항에 있어서, 센스 가닥은 3' 말단의 말단 뉴클레오티드들 사이에 단일 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물.
  21. 제18항 또는 제19항에 있어서, 센스 가닥은 3' 말단의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물.
  22. 제1항 내지 제21항 중 어느 한 항에 있어서, 안티센스 가닥은 표 1 또는 표 2에 열거된 안티센스 서열로부터 선택된 서열을 포함하거나 이로 구성되는, RNAi 작제물.
  23. 제1항 내지 제22항 중 어느 한 항에 있어서, 안티센스 가닥은 서열번호 715, 서열번호 732, 서열번호 733, 서열번호 738, 서열번호 754, 서열번호 761, 서열번호 763, 서열번호 764, 서열번호 766, 서열번호 809, 서열번호 810, 서열번호 814, 서열번호 841, 서열번호 848, 서열번호 851, 서열번호 862, 서열번호 916, 서열번호 1057, 서열번호 1078, 서열번호 2919, 서열번호 2926, 서열번호 2946, 서열번호 2949, 서열번호 2953, 및 서열번호 2956으로부터 선택된 서열을 포함하거나 이로 구성되는, RNAi 작제물.
  24. 제1항 내지 제23항 중 어느 한 항에 있어서, 센스 가닥은 표 1 또는 표 2에 열거된 센스 서열로부터 선택된 서열을 포함하거나 이로 구성되는, RNAi 작제물.
  25. 제24항에 있어서, 센스 가닥은 서열번호 46, 서열번호 63, 서열번호 64, 서열번호 69, 서열번호 85, 서열번호 92, 서열번호 94, 서열번호 95, 서열번호 97, 서열번호 140, 서열번호 141, 서열번호 145, 서열번호 172, 서열번호 179, 서열번호 182, 서열번호 193, 서열번호 247, 서열번호 388, 서열번호 390, 서열번호 391, 서열번호 409, 서열번호 2808, 및 서열번호 2820으로부터 선택된 서열을 포함하거나 이로 구성되는, RNAi 작제물.
  26. 제1항 내지 제25항 중 어느 한 항에 있어서,
    (i) 센스 가닥은 서열번호 46의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 715의 서열을 포함하거나 이로 구성되거나,
    (ii) 센스 가닥은 서열번호 63의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 732의 서열을 포함하거나 이로 구성되거나,
    (iii) 센스 가닥은 서열번호 64의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 733의 서열을 포함하거나 이로 구성되거나,
    (iv) 센스 가닥은 서열번호 69의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 738의 서열을 포함하거나 이로 구성되거나,
    (v) 센스 가닥은 서열번호 85의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 754의 서열을 포함하거나 이로 구성되거나,
    (vi) 센스 가닥은 서열번호 92의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 761의 서열을 포함하거나 이로 구성되거나,
    (vii) 센스 가닥은 서열번호 94의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 763의 서열을 포함하거나 이로 구성되거나,
    (viii) 센스 가닥은 서열번호 95의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 764의 서열을 포함하거나 이로 구성되거나,
    (ix) 센스 가닥은 서열번호 97의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 766의 서열을 포함하거나 이로 구성되거나,
    (x) 센스 가닥은 서열번호 140의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 809의 서열을 포함하거나 이로 구성되거나,
    (xi) 센스 가닥은 서열번호 141의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 810의 서열을 포함하거나 이로 구성되거나,
    (xii) 센스 가닥은 서열번호 145의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 814의 서열을 포함하거나 이로 구성되거나,
    (xiii) 센스 가닥은 서열번호 172의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 841의 서열을 포함하거나 이로 구성되거나,
    (xiv) 센스 가닥은 서열번호 179의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 848의 서열을 포함하거나 이로 구성되거나,
    (xv) 센스 가닥은 서열번호 182의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 851의 서열을 포함하거나 이로 구성되거나,
    (xvi) 센스 가닥은 서열번호 193의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 862의 서열을 포함하거나 이로 구성되거나, 또는
    (xvii) 센스 가닥은 서열번호 247의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 916의 서열을 포함하거나 이로 구성되는, RNAi 작제물.
  27. 제1항 내지 제25항 중 어느 한 항에 있어서,
    (i) 센스 가닥은 서열번호 409의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 1078의 서열을 포함하거나 이로 구성되거나,
    (ii) 센스 가닥은 서열번호 388의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 1057의 서열을 포함하거나 이로 구성되거나,
    (iii) 센스 가닥은 서열번호 2808의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 2926의 서열을 포함하거나 이로 구성되거나,
    (iv) 센스 가닥은 서열번호 2820의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 2946의 서열을 포함하거나 이로 구성되거나,
    (v) 센스 가닥은 서열번호 391의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 2949의 서열을 포함하거나 이로 구성되거나,
    (vi) 센스 가닥은 서열번호 390의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 2956의 서열을 포함하거나 이로 구성되거나,
    (vii) 센스 가닥은 서열번호 179의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 2919의 서열을 포함하거나 이로 구성되거나,
    (viii) 센스 가닥은 서열번호 388의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 2953의 서열을 포함하거나 이로 구성되거나, 또는
    (ix) 센스 가닥은 서열번호 388의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 1057의 서열을 포함하거나 이로 구성되는, RNAi 작제물.
  28. 제27항에 있어서,
    (i) 센스 가닥은 서열번호 3078에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3337에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나,
    (ii) 센스 가닥은 서열번호 3080에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3339에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나,
    (iii) 센스 가닥은 서열번호 3163에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3441에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나,
    (iv) 센스 가닥은 서열번호 3183에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3469에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나,
    (v) 센스 가닥은 서열번호 3076에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3472에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나,
    (vi) 센스 가닥은 서열번호 3077에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3484에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나,
    (vii) 센스 가닥은 서열번호 2051에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3545에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나,
    (viii) 센스 가닥은 서열번호 3080에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3481에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나,
    (ix) 센스 가닥은 서열번호 3188에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3339에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나,
    (x) 센스 가닥은 서열번호 3080에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3476에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되거나, 또는
    (xi) 센스 가닥은 서열번호 3223에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되고, 안티센스 가닥은 서열번호 3517에 따른 변형된 뉴클레오티드의 서열을 포함하거나 이로 구성되는, RNAi 작제물.
  29. 제1항 내지 제28항 중 어느 한 항에 있어서, RNAi 작제물은 표 1 내지 24에 열거된 이중체 화합물 중 어느 하나인, RNAi 작제물.
  30. 제29항에 있어서, RNAi 작제물은 D-2078, D-2079, D-2081, D-2182, D-2196, D-2238, D-2241, D-2243, D-2246, D-2255, D-2258, D-2301, D-2316, D-2317, D-2329, D-2332, D-2341, D-2344, D-2356, D-2357, D-2399, 또는 D-2510인, RNAi 작제물.
  31. 제30항에 있어서, RNAi 작제물은 D-2079, D-2081, D-2196, D-2238, D-2241, D-2255, D-2258, D-2317, D-2332, D-2357, 또는 D-2399인, RNAi 작제물.
  32. 세포에서 인간 MARC1 유전자의 발현을 억제하기 위한 RNAi 작제물로서, 상기 RNAi 작제물은, 하이브리드화하여 약 15 내지 약 30개 염기쌍 길이의 이중체 영역을 형성하는 센스 가닥 및 안티센스 가닥을 포함하고, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1205 내지 1250 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함하는, RNAi 작제물.
  33. 제32항에 있어서, 안티센스 가닥의 영역은 서열번호 1의 뉴클레오티드 1209 내지 1239 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 포함하는, RNAi 작제물.
  34. 제32항 또는 제33항에 있어서, 안티센스 가닥의 영역은 CAUCUAAUAUUCCAG(서열번호 3656)의 서열을 포함하는, RNAi 작제물.
  35. 제32항에 있어서, RNAi 작제물은 D-2063, D-2066, D-2076, D-2077, D-2078, D-2080, D-2081, D-2108, D-2113, D-2142, D-2240, D-2241, D-2243, D-2245, D-2246, D-2248, D-2250, D-2251, D-2253, D-2255, D-2256, D-2258, D-2259, D-2261, D-2264, D-2265, D-2268, D-2269, D-2270, D-2271, D-2301, D-2309, D-2311, D-2312, D-2314, D-2316, D-2317, D-2319, D-2321, D-2322, D-2324, D-2326, D-2327, D-2329, D-2331, D-2332, D-2334, D-2336, D-2337, D-2339, D-2341, D-2342, D-2344, D-2346, D-2347, D-2349, D-2351, D-2352, D-2354, D-2356, D-2357, D-2376, D-2380, D-2393, D-2395, D-2396, D-2431, D-2436, D-2437, D-2440, D-2441, D-2444, D-2445, D-2447, D-2453, D-2518, D-2519, D-2520, D-2521, D-2522, D-2523, D-2524, D-2525, D-2526, D-2527, D-2528, D-2529, D-2530, D-2531, D-2532, D-2533, D-2534, 또는 D-2535인, RNAi 작제물.
  36. 제35항에 있어서, RNAi 작제물은 D-2063, D-2066, D-2076, D-2077, D-2078, D-2080, D-2081, D-2108, D-2113, D-2142, 또는 D-2301인, RNAi 작제물.
  37. 세포에서 인간 MARC1 유전자의 발현을 억제하기 위한 RNAi 작제물로서, 상기 RNAi 작제물은, 하이브리드화하여 약 15 내지 약 30개 염기쌍 길이의 이중체 영역을 형성하는 센스 가닥 및 안티센스 가닥을 포함하고, 안티센스 가닥은 서열번호 1의 뉴클레오티드 1345 내지 1375 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함하는, RNAi 작제물.
  38. 제37항에 있어서, 안티센스 가닥의 영역은 UGGGACAUUGAAGCA(서열번호 3657)의 서열을 포함하는, RNAi 작제물.
  39. 제37항에 있어서, RNAi 작제물은 D-2042, D-2043, D-2047, D-2052, D-2158, D-2162, D-2169, D-2182, D-2183, D-2184, D-2185, D-2186, D-2187, D-2189, D-2211, D-2213, D-2304, D-2305, D-2306, D-2307, D-2308, D-2384, D-2384, D-2385, D-2386, D-2387, D-2388, D-2389, D-2390, D-2391, D-2392, D-2399, D-2400, D-2401, D-2402, D-2403, D-2488, D-2494, D-2500, D-2506, D-2512, D-2538, D-2539, D-2540, 또는 D-2541인, RNAi 작제물.
  40. 제39항에 있어서, RNAi 작제물은 D-2042, D-2043, D-2047, D-2052, D-2304, D-2305, D-2306, D-2307, 또는 D-2308인, RNAi 작제물.
  41. 세포에서 인간 MARC1 유전자의 발현을 억제하기 위한 RNAi 작제물로서, 상기 RNAi 작제물은, 하이브리드화하여 약 15 내지 약 30개 염기쌍 길이의 이중체 영역을 형성하는 센스 가닥 및 안티센스 가닥을 포함하고, 안티센스 가닥은 서열번호 1의 뉴클레오티드 2039 내지 2078 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 갖는 영역을 포함하는, RNAi 작제물.
  42. 제41항에 있어서, 안티센스 가닥의 영역은 서열번호 1의 뉴클레오티드 2048 내지 2074 중 적어도 15개의 연속 뉴클레오티드의 서열에 실질적으로 상보적인 서열을 포함하는, RNAi 작제물.
  43. 제41항 또는 제42항에 있어서, 안티센스 가닥의 영역은 AUCAGAUCUUAGAGU(서열번호 3658)의 서열을 포함하는, RNAi 작제물.
  44. 제41항에 있어서, RNAi 작제물은 D-2045, D-2065, D-2079, D-2082, D-2105, D-2106, D-2137, D-2143, D-2166, D-2173, D-2193, D-2242, D-2247, D-2252, D-2257, D-2260, D-2262, D-2266, D-2272, D-2273, D-2302, D-2303, D-2310, D-2313, D-2315, D-2318, D-2320, D-2323, D-2325, D-2328, D-2330, D-2333, D-2335, D-2338, D-2340, D-2343, D-2345, D-2348, D-2350, D-2353, D-2355, D-2358, D-2394, D-2397, D-2454, D-2455, D-2456, D-2457, D-2458, D-2459, D-2460, D-2463, D-2465, D-2465, D-2468, D-2470, D-2472, D-2473, D-2477, D-2487, D-2493, D-2499, D-2505, D-2511, D-2552, D-2553, D-2554, D-2555, D-2556, 또는 D-2557인, RNAi 작제물.
  45. 제44항에 있어서, RNAi 작제물은 D-2045, D-2065, D-2079, D-2082, D-2105, D-2106, D-2137, D-2143, D-2302, 또는 D-2303인, RNAi 작제물.
  46. 제32항 내지 제45항 중 어느 한 항에 있어서, 이중체 영역은 약 19 내지 약 21개 염기쌍 길이인, RNAi 작제물.
  47. 제32항 내지 제46항 중 어느 한 항에 있어서, 센스 가닥 및 안티센스 가닥은 각각 독립적으로 약 19 내지 약 30개 뉴클레오티드 길이인, RNAi 작제물.
  48. 제47항에 있어서, 센스 가닥 및 안티센스 가닥은 각각 독립적으로 약 19 내지 약 23개 뉴클레오티드 길이인, RNAi 작제물.
  49. 제32항 내지 제48항 중 어느 한 항에 있어서, RNAi 작제물은 하나 또는 두 개의 평활 말단을 포함하는, RNAi 작제물.
  50. 제32항 내지 제48항 중 어느 한 항에 있어서, RNAi 작제물은 1 내지 4개의 짝없는 뉴클레오티드의 하나 또는 두 개의 뉴클레오티드 오버행을 포함하는, RNAi 작제물.
  51. 제50항에 있어서, 뉴클레오티드 오버행은 2개의 짝없는 뉴클레오티드를 갖는, RNAi 작제물.
  52. 제50항 또는 제51항에 있어서, RNAi 작제물은 센스 가닥의 3' 말단, 안티센스 가닥의 3' 말단, 또는 센스 가닥 및 안티센스 가닥 둘 다의 3' 말단에 뉴클레오티드 오버행을 포함하는, RNAi 작제물.
  53. 제32항 내지 제52항 중 어느 한 항에 있어서, RNAi 작제물은 적어도 하나의 변형된 뉴클레오티드를 포함하는, RNAi 작제물.
  54. 제53항에 있어서, 변형된 뉴클레오티드는 2'-변형된 뉴클레오티드인, RNAi 작제물.
  55. 제54항에 있어서, 변형된 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알킬 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, BNA, 데옥시리보뉴클레오티드, 또는 이들의 조합인, RNAi 작제물.
  56. 제53항에 있어서, 센스 및 안티센스 가닥의 모든 뉴클레오티드는 변형된 뉴클레오티드인, RNAi 작제물.
  57. 제56항에 있어서, 변형된 뉴클레오티드는 2'-O-메틸 변형된 뉴클레오티드, 2'-플루오로 변형된 뉴클레오티드, 또는 이들의 조합인, RNAi 작제물.
  58. 제32항 내지 제57항 중 어느 한 항에 있어서, 센스 가닥은 이의 3' 말단, 이의 5' 말단, 또는 이의 3' 및 5' 말단 둘 다에서 말단 뉴클레오티드로서 무염기 뉴클레오티드를 포함하는, RNAi 작제물.
  59. 제58항에 있어서, 무염기 뉴클레오티드는 3'-3' 뉴클레오티드간 연결 또는 5'-5' 뉴클레오티드간 연결을 통해 인접 뉴클레오티드에 연결되는, RNAi 작제물.
  60. 제32항 내지 제59항 중 어느 한 항에 있어서, 센스 가닥, 안티센스 가닥, 또는 센스 및 안티센스 가닥 둘 다는 1개 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물.
  61. 제60항에 있어서, 안티센스 가닥은 3' 및 5' 말단 둘 다의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물.
  62. 제60항 또는 제61항에 있어서, 센스 가닥은 3' 말단의 말단 뉴클레오티드들 사이에 단일 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물.
  63. 제60항 또는 제61항에 있어서, 센스 가닥은 3' 말단의 말단 뉴클레오티드들 사이에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물.
  64. 제1항 내지 제63항 중 어느 한 항에 있어서, RNAi 작제물은 리간드를 추가로 포함하는, RNAi 작제물.
  65. 제64항에 있어서, 리간드는 콜레스테롤 모이어티, 비타민, 스테로이드, 담즙산, 폴레이트 모이어티, 지방산, 탄수화물, 글리코시드, 또는 항체 또는 이의 항원 결합 단편을 포함하는, RNAi 작제물.
  66. 제64항에 있어서, 리간드는 갈락토스, 갈락토사민, 또는 N-아세틸-갈락토사민을 포함하는, RNAi 작제물.
  67. 제66항에 있어서, 리간드는 다가 갈락토스 모이어티 또는 다가 N-아세틸-갈락토사민 모이어티를 포함하는, RNAi 작제물.
  68. 제67항에 있어서, 다가 갈락토스 모이어티 또는 다가 N-아세틸-갈락토사민 모이어티는 3가 또는 4가인, RNAi 작제물.
  69. 제64항 내지 제68항 중 어느 한 항에 있어서, 리간드는 임의로 링커를 통해 센스 가닥에 공유적으로 부착되는, RNAi 작제물.
  70. 제69항에 있어서, 리간드는 센스 가닥의 5' 말단에 공유적으로 부착되는, RNAi 작제물.
  71. 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물 및 약제학적으로 허용가능한 담체 또는 부형제를 포함하는 약제학적 조성물.
  72. 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물 또는 제71항의 약제학적 조성물을 mARC1 단백질 발현의 감소를 필요로 하는 환자에게 투여하는 단계를 포함하는, 환자의 mARC1 단백질 발현을 감소시키는 방법.
  73. 제72항에 있어서, 간세포에서 mARC1의 발현 수준은 RNAi 작제물 또는 약제학적 조성물을 투여받지 않은 환자에서의 mARC1 발현 수준과 비교하여 RNAi 작제물 또는 약제학적 조성물의 투여 후 환자에서 감소되는, 방법.
  74. 제72항에 있어서, 환자는 심혈관 질환, 비알코올성 지방간 질환, 비알코올성 지방간염, 또는 간경변으로 진단되거나 이에 걸릴 위험이 있는, 방법.
  75. 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물 또는 제71항의 약제학적 조성물을 혈청 콜레스테롤의 감소를 필요로 하는 환자에게 투여하는 단계를 포함하는, 환자의 혈청 콜레스테롤을 감소시키는 방법.
  76. 제75항에 있어서, 혈청 콜레스테롤은 비-HDL 콜레스테롤 또는 LDL 콜레스테롤인, 방법.
  77. 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물 또는 제71항의 약제학적 조성물을 지방간 질환의 치료, 예방, 또는 발병 감소를 필요로 하는 환자에게 투여하는 단계를 포함하는, 환자의 지방간 질환을 치료하거나, 예방하거나, 이의 발병을 감소시키는 방법.
  78. 제77항에 있어서, 지방간 질환은 비알코올성 지방간 질환 또는 비알코올성 지방간염인, 방법.
  79. 제77항 또는 제78항에 있어서, 환자는 제2형 당뇨병, 대사 장애, 또는 비만으로 진단된, 방법.
  80. 제77항 또는 제78항에 있어서, 환자는 비-HDL 콜레스테롤 또는 트리글리세리드의 수준이 상승된, 방법.
  81. 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물 또는 제71항의 약제학적 조성물을 간 섬유증의 치료, 예방, 또는 감소를 필요로 하는 환자에게 투여하는 단계를 포함하는, 환자의 간 섬유증을 치료하거나, 예방하거나, 감소시키는 방법.
  82. 제81항에 있어서, 환자에 대한 RNAi 작제물 또는 약제학적 조성물의 투여는 간경변을 예방하거나 지연시키는, 방법.
  83. 제81항 또는 제82항에 있어서, 환자는 비알코올성 지방간 질환 또는 비알코올성 지방간염으로 진단된, 방법.
  84. 제72항 내지 제83항 중 어느 한 항에 있어서, RNAi 작제물 또는 약제학적 조성물은 비경구 투여 경로를 통해 환자에게 투여되는, 방법.
  85. 제84항에 있어서, 비경구 투여 경로는 정맥내 또는 피하인, 방법.
  86. 혈청 콜레스테롤의 감소를 필요로 하는 환자에서 이를 위한 방법에 사용하기 위한 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물.
  87. 제86항에 있어서, 혈청 콜레스테롤은 비-HDL 콜레스테롤 또는 LDL 콜레스테롤인, RNAi 작제물.
  88. 지방간 질환의 치료, 예방, 또는 발병 위험의 감소를 필요로 하는 환자에서 이를 위한 방법에 사용하기 위한 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물.
  89. 제88항에 있어서, 지방간 질환은 비알코올성 지방간 질환 또는 비알코올성 지방간염인, RNAi 작제물.
  90. 간 섬유증의 치료, 예방, 또는 감소를 필요로 하는 환자에서 이를 위한 방법에 사용하기 위한 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물.
  91. 제90항에 있어서, 환자는 비알코올성 지방간 질환 또는 비알코올성 지방간염으로 진단된, RNAi 작제물.
  92. 혈청 콜레스테롤의 감소를 필요로 하는 환자에서 이를 위한 의약의 제조에 있어서 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물의 용도.
  93. 제92항에 있어서, 혈청 콜레스테롤은 비-HDL 콜레스테롤 또는 LDL 콜레스테롤인, 용도.
  94. 지방간 질환의 치료, 예방, 또는 발병 위험의 감소를 필요로 하는 환자에서 이를 위한 의약의 제조에 있어서 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물의 용도.
  95. 제94항에 있어서, 지방간 질환은 비알코올성 지방간 질환 또는 비알코올성 지방간염인, 용도.
  96. 간 섬유증의 치료, 예방, 또는 감소를 필요로 하는 환자에서 이를 위한 의약의 제조에 있어서 제1항 내지 제70항 중 어느 한 항의 RNAi 작제물의 용도.
  97. 제96항에 있어서, 환자는 비알코올성 지방간 질환 또는 비알코올성 지방간염으로 진단된, 용도.
KR1020237008366A 2020-08-13 2021-08-12 MARC1 발현을 억제하기 위한 RNAi 작제물 및 방법 KR20230046319A (ko)

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Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5981505A (en) 1993-01-26 1999-11-09 The Trustees Of The University Of Pennsylvania Compositions and methods for delivery of genetic material
US5837533A (en) 1994-09-28 1998-11-17 American Home Products Corporation Complexes comprising a nucleic acid bound to a cationic polyamine having an endosome disruption agent
US5840710A (en) 1994-12-09 1998-11-24 Genzyme Corporation Cationic amphiphiles containing ester or ether-linked lipophilic groups for intracellular delivery of therapeutic molecules
EP1489184A1 (en) 1995-06-07 2004-12-22 Inex Pharmaceutical Corp. Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US7422902B1 (en) 1995-06-07 2008-09-09 The University Of British Columbia Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
US6217900B1 (en) 1997-04-30 2001-04-17 American Home Products Corporation Vesicular complexes and methods of making and using the same
ATE321882T1 (de) 1997-07-01 2006-04-15 Isis Pharmaceuticals Inc Zusammensetzungen und verfahren zur verabreichung von oligonukleotiden über die speiseröhre
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US6693187B1 (en) 2000-10-17 2004-02-17 Lievre Cornu Llc Phosphinoamidite carboxlates and analogs thereof in the synthesis of oligonucleotides having reduced internucleotide charge
US7109165B2 (en) 2001-05-18 2006-09-19 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US20030130186A1 (en) 2001-07-20 2003-07-10 Chandra Vargeese Conjugates and compositions for cellular delivery
US9181551B2 (en) 2002-02-20 2015-11-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
WO2003093449A2 (en) 2002-05-06 2003-11-13 Nucleonics, Inc. Methods for delivery of nucleic acids
DK1620544T3 (en) 2003-04-17 2019-01-14 Alnylam Pharmaceuticals Inc MODIFIED iRNA AGENTS
US8017762B2 (en) 2003-04-17 2011-09-13 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
WO2008131419A2 (en) 2007-04-23 2008-10-30 Alnylam Pharmaceuticals, Inc. Glycoconjugates of rna interference agents
WO2009073809A2 (en) 2007-12-04 2009-06-11 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
WO2009099991A2 (en) * 2008-01-31 2009-08-13 The Brigham And Women's Hospital, Inc. Treatment of cancer
AR090905A1 (es) 2012-05-02 2014-12-17 Merck Sharp & Dohme Conjugados que contienen tetragalnac y peptidos y procedimientos para la administracion de oligonucleotidos, composicion farmaceutica
AU2014259755B2 (en) * 2013-05-01 2018-08-30 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein (a) expression
EP3011028B1 (en) 2013-06-21 2019-06-12 Ionis Pharmaceuticals, Inc. Compositions and methods for modulation of target nucleic acids
EP3356415B1 (en) 2015-09-29 2024-05-01 Amgen Inc. Asgr inhibitors for reduzing cholesterol levels
CA3122393A1 (en) 2018-12-10 2020-06-18 Amgen Inc. Chemically-modified rnai constructs and uses thereof
WO2021237097A1 (en) * 2020-05-21 2021-11-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting marc1 gene expression

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