KR20200097299A - Pnpla3 발현을 억제하기 위한 rnai 작제물 - Google Patents
Pnpla3 발현을 억제하기 위한 rnai 작제물 Download PDFInfo
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- KR20200097299A KR20200097299A KR1020207019521A KR20207019521A KR20200097299A KR 20200097299 A KR20200097299 A KR 20200097299A KR 1020207019521 A KR1020207019521 A KR 1020207019521A KR 20207019521 A KR20207019521 A KR 20207019521A KR 20200097299 A KR20200097299 A KR 20200097299A
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- rnai construct
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Abstract
본 발명은 PNPLA3 유전자의 발현을 감소시키기 위한 RNAi 작제물에 관한 것이다. 간 질환, 비알코올성 지방간 질환(NAFLD)을 치료 또는 예방하기 위해 이러한 RNAi 작제물을 사용하는 방법이 또한 기술되어 있다.
Description
관련 출원
본 출원은 2017년 12월 12일자로 출원된 미국 가특허 출원 제62/597,841호를 우선권으로 주장하며, 그 내용은 본원에 참조로 포함된다.
서열 목록
본 출원은 ASCII 포맷으로 전자 제출된 서열 목록을 포함하며, 그 전문이 본원에 참조로 포함된다. 2018년 12월 12일에 작성된 상기 ASCII 사본의 명칭은 A-2219-WO-PCT_SL.txt이며, 크기는 708,961 바이트이다. 서열 목록의 전자 형식에서의 정보는 그 전체가 본 명세서에 참조로 포함된다.
기술분야
본 발명은 파타틴-유사 포스포리파제 도메인-함유 3(PNPLA3)의 간 발현을 조절하기 위한 조성물 및 방법에 관한 것이고, 특히 본 발명은 RNA 간섭을 통해 PNPLA3 발현을 감소시키기 위한 핵산-기반 치료제 및 비알코올성 지방간 질환(NAFLD)과 같은 간 질환을 치료 또는 예방하기 위해 상기 핵산-기반 치료제를 사용하는 방법에 관한 것이다.
본 출원은 ASCII 포맷으로 전자 제출된 서열 목록을 포함하며, 그 전문이 본원에 참조로 포함된다. 2018년 12월 12일에 작성된 상기 ASCII 사본의 명칭은 A-2219-WO-PCT_SL.txt이며, 크기는 708,961 바이트이다.
다양한 간 병리를 포함하여, 비알코올성 지방간 질환(NAFLD)은 세계에서 가장 흔한 만성 간 질환이며, 그의 유병률은 지난 20년 동안 2배가 되었으며, 현재 세계 인구의 약 20%에 영향을 미치는 것으로 추정된다(Sattar et al. (2014) BMJ 349:g4596; Loomba and Sanyal (2013) Nature Reviews Gastroenterology & hepatology 10(11):686-690; Kim and Kim (2017) Clin Gastroenterol Hepatol 15(4):474-485; Petta et al. (2016) Dig Liver Dis 48(3):333-342). NAFLD는 간에서 트리글리세리드의 축적으로 시작하며, 1) 상당한 알코올 소비 이력이 없고 2) 다른 유형의 간 질환의 진단이 제외된 개체에서 간세포의 5% 초과에서 세포질내 지방구(cytoplasmic lipid droplets)의 존재로 정의된다(Zhu et al (2016) World J Gastroenterol 22(36):8226-33; Rinella (2015) JAMA 313(22):2263-73; Yki-Jarvinen (2016) Diabetologia 59(6):1104-11). 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(Rinella, 상동). 2015년 현재, 7500만명 내지 1억명의 미국인이 NAFLD를 앓고 있는 것으로 예상되며; NASH는 NAFLD 진단의 대략 10~30%를 차지한다(Rinella, supra; Younossi et al (2016) Hepatology 64(5):1577-1586).
이전에 아디포누트린(ADPN) 및 칼슘-비의존적 포스포리파제 A2- 엡실론(iPLA(2)ε)으로 알려진 파타틴-유사 포스포리파제 도메인-함유 3(PNPLA3)은 유형 II 막관통 단백질이다(Wilson et al (2006) J Lipid Res 47(9):1940-9; Jenkins et al (2004) J Biol Chem 279(47):48968-75). 마우스에서 지방생성 동안 유도된 막-결합, 지방-풍부 단백질로서 지방 세포에서 초기에 확인되며, 이는 이제 간을 포함한 다른 조직에서 발현되는 것이 잘 특징화된다(Wilson et al, supra; Baulande et al (2001) J Biol Chem 276(36):33336-44; Moldes et al. (2006) Eur J Endocrinol 155(3):461-8; Faraj et al. (2006) J Endocrinol 191(2):427-35; Liu et al (2004) J Clin Endocrinol Metab 89(6):2684-9; Lake et al (2005) J Lipid Res 46(11):2477-87). 무-세포 생화학적 시스템에서, 재조합 PNPLA3 단백질은 트리아실글리세롤 리파제 또는 트랜스아실화 활성을 나타낼 수 있다(Jenkins et al., supra; Kumari et al (2012) Cell Metab 15(5):691-702; He et al (2010) J Biol Chem 285(9):6706-15). 간세포에서, PNPLA3은 소포체 및 지질 막에서 발현되며, 트리아실글리세롤 가수분해효소 활성을 주로 나타낸다(He et al., supra; Huang et al (2010) Proc Natl Acad Sci USA 107(17):7892-7; Ruhanen et al (2014) J Lipid Res 55(4):739-46; Pingitore et al. (2014) Biochim Biophys Acta 1841(4):574-80). 분비 신호가 없지만, 데이터는 PNPLA3이 분비되고 이황화-결합 의존성 다량체로서 인간 혈장에서 발견될 수 있음을 나타낸다(Winberg et al. (2014) Biochem Biophys Res Commun 446(4):1114-9). 따라서, PNPLA3 기능을 표적으로 하는 신규 치료제는 PNPLA3 수준을 감소시키고 비알코올성 지방간 질환과 같은 간 질환을 치료하는 신규한 접근법을 대표한다.
본 발명은 PNPLA3 유전자를 표적으로 하고 간 세포에서 PNPLA3의 발현을 감소시키는 RNAi 작제물의 설계 및 생성에 부분적으로 기초한다. PNPLA3 발현의 서열 특이적 억제는 PNPLA3 발현과 관련된 병태, 예컨대 간-관련 질환, 예컨대, 예를 들어, 단순 지방간(지방증), 비알코올성 지방간염(NASH), 간경변(비가역적, 진행성 간 흉터) 또는 PNPLA3 관련 비만을 치료 또는 예방하는데 유용하다. 따라서, 일 실시형태에서, 본 발명은 센스 가닥 및 안티센스 가닥을 포함하는 RNAi 작제물을 제공하며, 상기 안티센스 가닥은 PNPLA3 mRNA 서열에 상보적인 서열을 갖는 영역을 포함한다. 특정 실시형태에서, 안티센스 가닥은 표 1 또는 표 2에 열거된 안티센스 서열로부터의 적어도 15개의 인접 뉴클레오티드를 갖는 영역을 포함한다. 일부 실시형태에서, 본 발명의 RNAi는 상기 변화를 함유하지 않는 참고 대립유전자에 대한 PNPLA3-rs738409, PNPLA3-rs738408, 및/또는 PNPLA3-rs738409-rs738408 소수 대립유전자를 선택적으로 억제한다.
일부 실시형태에서, 본 명세서에 기재된 RNAi 작제물의 센스 가닥은 안티센스 가닥의 서열에 충분히 상보적인 서열을 포함하여 길이가 약 15 내지 약 30개의 염기쌍인 이중체 영역을 형성한다. 상기 및 다른 실시형태에서, 센스 및 안티센스 가닥은 각각 길이가 약 15 내지 약 30개의 뉴클레오티드이다. 일부 실시형태에서, RNAi 작제물은 적어도 하나의 평활 말단을 포함한다. 다른 실시형태에서, RNAi 작제물은 적어도 하나의 뉴클레오티드 오버행을 포함한다. 상기 뉴클레오티드 오버행은 적어도 1 내지 6개의 짝없는 뉴클레오티드를 포함할 수 있고, 센스 가닥의 3' 말단, 안티센스 가닥의 3' 말단, 또는 센스 및 안티센스 가닥 둘다의 3' 말단에 위치될 수 있다. 특정 실시형태에서, RNAi 작제물은 센스 가닥의 3' 말단 및 안티센스 가닥의 3' 말단에 2개의 짝없는 뉴클레오티드의 오버행을 포함한다. 다른 실시형태에서, RNAi 작제물은 안티센스 가닥의 3' 말단에 2개의 짝없는 뉴클레오티드의 오버행 및 센스 가닥의 3' 말단/안티센스 가닥의 5' 말단의 평활 말단을 포함한다.
본 발명의 RNAi 작제물은 리보스 고리, 핵염기 또는 포스포디에스테르 백본에 변형을 갖는 뉴클레오티드를 포함하는 하나 이상의 변형된 뉴클레오티드를 포함할 수 있다. 일부 실시형태에서, RNAi 작제물은 하나 이상의 2'-변형된 뉴클레오티드를 포함한다. 상기 2'-변형된 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, 이환식 핵산(BNA), 글리콜 핵산(GNAs), 역 염기(예를 들어, 역 아데노신) 또는 이들의 조합을 포함할 수 있다. 특정 일 실시형태에서, RNAi 작제물은 하나 이상의 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 또는 이들의 조합을 포함한다. 일부 실시형태에서, RNAi 작제물의 센스 및 안티센스 가닥의 모든 뉴클레오티드는 변형된 뉴클레오티드이다.
일부 실시형태에서, RNAi 작제물은 적어도 하나의 골격 변형, 예컨대 변형된 뉴클레오티드간 또는 뉴클레오시드간 연결을 포함한다. 특정 실시형태에서, 본 명세서에 기재된 RNAi 작제물은 적어도 하나의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 특정 실시형태에서, 포스포로티오에이트 뉴클레오티드간 연결은 센스 및/또는 안티센스 가닥의 3' 또는 5' 말단에 위치될 수 있다.
일부 실시형태에서, 본 발명의 RNAi 작제물의 안티센스 가닥 및/또는 센스 가닥은 표 1 또는 2에 열거된 안티센스 및 센스 서열을 포함하거나, 이들로 구성될 수 있다. 특정 실시형태에서, RNAi 작제물은 표 1 내지 2 중 어느 하나에 열거된 이중체 화합물 중 어느 하나일 수 있다.
도 1a~1d는 용량-의존적 mRNA 녹다운 및 생체내 기능적 내구성 둘 다에 대한 5개의 siRNA 분자의 스크리닝을 도시한다.
도 2a~2g는 마우스 생체내 PNPLA3 siRNA 분자의 효과, 간 중량, 인간 PNPLA3 발현의 확인, 간 트리글리세리드 함량, 혈청 TIMP1 수준, 및 지방증 또는 염증의 조직학적 징후를 도시한다.
도 3a~3g는 생체내 PNPLA3 siRNA 분자의 효과, 간 중량, 인간 PNPLA3 발현의 확인, 간 트리글리세리드 함량, 혈청 TIMP1 수준, 및 지방증 또는 염증의 조직학적 징후를 도시한다.
도 4a~4d는 PNPLA3rs738409-rs738408의 과발현, 간 트리글리세리드 함량, 혈청 TIMP1 수준, 및 지방증 또는 염증의 조직학적 징후로 인해 질환-관련 표현형을 구제하는, PNPLA3rs738409-rs738408-특이적 siRNA 분자의 능력을 도시한다.
도 5a~5l은 초기 섬유증의 발생을 예방하기 위한 PNPLA3rs738409-rs738408-특이적 siRNA 분자의 능력을 도시한다.
도 2a~2g는 마우스 생체내 PNPLA3 siRNA 분자의 효과, 간 중량, 인간 PNPLA3 발현의 확인, 간 트리글리세리드 함량, 혈청 TIMP1 수준, 및 지방증 또는 염증의 조직학적 징후를 도시한다.
도 3a~3g는 생체내 PNPLA3 siRNA 분자의 효과, 간 중량, 인간 PNPLA3 발현의 확인, 간 트리글리세리드 함량, 혈청 TIMP1 수준, 및 지방증 또는 염증의 조직학적 징후를 도시한다.
도 4a~4d는 PNPLA3rs738409-rs738408의 과발현, 간 트리글리세리드 함량, 혈청 TIMP1 수준, 및 지방증 또는 염증의 조직학적 징후로 인해 질환-관련 표현형을 구제하는, PNPLA3rs738409-rs738408-특이적 siRNA 분자의 능력을 도시한다.
도 5a~5l은 초기 섬유증의 발생을 예방하기 위한 PNPLA3rs738409-rs738408-특이적 siRNA 분자의 능력을 도시한다.
본 발명은 파타틴-유사 포스포리파제 도메인-함유 3(PNPLA3) 유전자의 발현을 조절하기 위한 조성물 및 방법에 관한 것이다. 일부 실시형태에서, 유전자는 세포 또는 대상체, 예컨대 포유동물(예를 들어, 인간)내에 있을 수 있다. 일부 실시형태에서, 본 발명의 조성물은 PNPLA3 mRNA를 표적으로 하고, 세포 또는 포유동물에서 PNPLA3 발현을 감소시키는 RNAi 작제물을 포함한다. 상기 RNAi 작제물은 다양한 형태의 간-관련 질환, 예컨대, 예를 들어, 단순 지방간(지방증), 비알코올성 지방간염(NASH), 간경변(비가역적, 진행성 간 흉터) 또는 PNPLA3 관련 비만을 치료 또는 예방하는데 유용하다.
2008년에, 비유사(nonsynomonous) 서열 변이, 또는 단일 뉴클레오티드 다형성(SNPs)을 분석하는 NAFLD와 관련된 전장유전체 연관성분석(GWAS)은 PNPLA3에 변이체가 간 지방 함량과 유의하게 관련됨을 확인하였다(rs738409[G], I148M을 암호화함; PNPLA3-rs738409, PNPLA3-ma 또는 PNPLA3-소수 대립유전자로도 언급될 수 있음). 이 초기 보고서 이후, 후속 GWAS는 PNPLA3 rs738409를 NAFLD의 주요 유전적 결정 인자로 확인하는데, 이는 1) 간 손상에 대한 혈청 바이오마커, 알라닌 트랜스아미나제(ALT)의 수준 증가, 2) NAFLD 발생, 진행 및 심각성, 3) 비만 및 마른 개체 둘 다, 및 4) NAFLD: 지방증, NASH, 간경변 및 간세포 암종의 모든 단계와 유의하게 관련되어 있는 것으로 나타난 유일하게 공지된 SNP와 유의하게 관련되어 있다. 수많은 GWAS 간의 합의는 PNPLA3 rs738409와 NAFLD의 연관성이 연령, 성별, 인종, 대사 증후군, 체질량 지수, 인슐린 저항성 및 혈청 지질과 무관하다는 것을 나타낸다. 더욱이, 다수의 공급원으로부터의 통계 분석은 NAFLD 환자의 대략 50%가 PNPLA3 rs738409 돌연변이를 보유하는 것으로 추정한다. 환자는 PNPLA3 rs738409 돌연변이에 대해 동형접합성 또는 이형접합성일 수 있다. 또한, PNPLA3 rs738409 돌연변이를 갖는 환자는 종종 rs738408 돌연변이 3 염기쌍을 멀리 보유하고 있는 것으로 밝혀졌다(Tian et al (2010) Nature Genetics 42:21-23). 따라서, 환자는 PNPLA3-rs738409 소수 대립유전자, PNPLA3-rs738408 소수 대립유전자 또는 PNPLA3-rs738409-rs738408 이중 소수 대립유전자 돌연변이(PNPLA3-dma)를 가질 수 있다.
연구자들은 생체내에서 PNPLA3 기능을 탐구하기 위한 마우스 모델을 개발하였다. 현재까지, 검출가능한 대사 표현형은 Pnpla3-결핍 또는 Pnpla3 과발현의 결과로 확인되지 않았다. 대조적으로, 트랜스제닉 마우스 및 녹-인 마우스 둘 다에서 Pnpla3 I148M의 발현은 NAFLD와 유사하게 간 트리글리세리드 수준을 증가시켰다. 따라서, 조합된, 생체내 마우스 모델 데이터는 돌연변이 Pnpla3 I148M 단백질의 발현을 나타내며, 질환 표현형의 동인으로서의 야생형 단백질의 과-발현은 아니다. 이러한 발견은, NAFLD-영향 개체에서 소수 대립유전자의 높은 빈도 및 질환과의 우세한 연관성에 추가하여, NAFLD의 주요 치료 목표로서 PNPLA3 rs738409를 강조한다.
RNA 간섭(RNAi)은 외인성 RNA를 세포 내로 도입하여 단백질 발현의 결과적인 감소와 함께 표적화된 단백질을 암호화하는 mRNA의 특이적 분해를 초래하는 과정이다. RNAi 기술 및 간 전달 모두의 발전과 다른 RNAi-기반 요법으로 긍정적인 결과가 증가하는 것은 PNPLA3I148M을 직접 표적으로 함으로써 NAFLD를 치료적으로 치료할 수 있는 강력한 수단으로 RNAi를 제안한다. 다수의 GWAS는 NAFLD 발병, 진행 및 중증도(GWAS)에 대한 PNPLA3 rs738409의 용량-의존적 효과를 나타내고; 동형접합체 담체 대 이형접합체 담체의 경우, 배당률은 두 배 이상인 경향이 있지만, 이형접합체 대 야생형 개체의 경우에는 여전히 적어도 2배 더 높다. 따라서, 대립유전자 판별 특이성을 이용하여 PNPLA3을 사일런싱(silencing)시키는 것은 PNPLA3I148M 담체에서 간 트리글리세리드를 감소시키는 잠재적인 수단일 수 있지만, 이형접합체가 야생형 대립유전자의 사일런싱없이 이익을 얻을 수 있는 시나리오를 제시한다. 이러한 맥락에서, 본 발명자들은 PNPLA3I148M에 대한 SNP-특이적 짧은 간섭 RNA(siRNA)를 식별하고 시험관내 개념을 입증한다. 간암 세포주, Hep3B(참조 대립유전자, PNPLA3I148I에 대한 동형접합체) 및 HEPG2(소수 대립유전자, PNPLA3I148M에 대한 동형접합체) 둘 다를 사용하여, 본 발명자들은 특히 PNPLA3I148M 유전자 발현을 억제할 수 있는 siRNA 서열을 확인하였다. 이들 서열의 억제 효과는 PNPLA3I148I 또는 PNPLA3I148M을 과발현하는 차이니즈 햄스터 난소(CHO) 세포를 스크리닝함으로써 확인되었다. 생체내에서 인간 PNPLA3I148M을 과발현하기 위해 아데노-연관 바이러스(AAV)를 사용하여, 본 발명자들은 소수 대립유전자-특이적 SNP로 처리하는 것이 마우스에서 인간 PNPLA3I148M 발현을 분명히 감소시킬 뿐만 아니라 인간 PNPLA3I148M의 과발현에 의해 유도된 간 트리글리세리드 축적을 상당히 역전시켰음을 입증하였다.
본 명세서에 사용된 바와 같이, 용어 "RNAi 작제물"은 세포 내로 도입될 때 RNA 간섭 메카니즘을 통해 표적 유전자(예를 들어, PNPLA3)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 실시형태에서, RNAi 작제물은 이중체 영역을 형성하도록 하이브리드화하기 위해 서로에 대해 충분히 상보적인 인접 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"으로 지칭된다. "센스 가닥"은 안티센스 가닥의 영역에 실질적으로 상보적인 영역을 포함하는 가닥을 지칭한다. 일부 실시형태에서, 센스 가닥은 표적 서열과 실질적으로 동일한 서열을 갖는 영역을 포함할 수 있다.
일부 실시형태에서, 본 발명은 PNPLA3에 대한 RNAi이다. 일부 실시형태에서, 본 발명은 PNPLA3 rs738409 부위에서 결합하는 RNAi이다. 일부 실시형태에서, 본 발명은 PNPLA3 rs738408 부위에서 결합하는 RNAi이다. 일부 실시형태에서, 본 발명은 PNPLA3 rs738409 rs738408 부위 둘 다에서 결합하는 RNAi이다. 일부 실시형태에서, 본 발명은 천연 PNPLA3 서열(PNPLA3-ref)에 비해 PNPLA3 rs738409에 우선적으로 결합하는 RNAi이다. 일부 실시형태에서, 본 발명은 PNPLA3-ref 서열에 비해 PNPLA3 rs738408에 우선적으로 결합하는 RNAi이다. 일부 실시형태에서, 본 발명은 PNPLA3-ma에 비해 PNPLA3-dma에 우선적으로 결합하는 RNAi이다. 일부 실시형태에서, 본 발명은 표 1 또는 2에서 발견되는 임의의 서열을 함유하는 RNAi 분자이다.
이중-가닥 RNA 분자는 리보뉴클레오티드의 리보스 당, 염기 또는 백본 성분, 예컨대 본 명세서에 기술되거나 당 업계에 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.
본 명세서에 사용된 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 서열을 포함하는 폴리뉴클레오티드가 임의의 미스매치 없이 하나 또는 양쪽 모두의 뉴클레오티드 서열의 전체 길이에 걸쳐 제2 서열을 포함하는 폴리뉴클레오티드와 염기쌍을 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%, 99% 또는 100% 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, 2, 또는 1개 이하의 미스매치가 있으면, 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 본 명세서에서 사용되는 용어로서 완전히 상보적인 것으로 간주된다.
일부 실시형태에서, 안티센스 가닥의 영역은 표적 RNA 서열(예를 들어, PNPLA3 mRNA)의 영역에 완전히 상보적인 서열을 포함한다. 상기 이러한 실시형태에서, 센스 가닥은 안티센스 가닥의 서열에 완전히 상보적인 서열을 포함할 수 있다. 다른 이러한 실시형태에서, 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 실시형태에서, 임의의 미스매치는 말단 영역내에서 (예를 들어, 가닥의 5' 및/또는 3' 말단의 6, 5, 4, 3, 2, 또는 1개의 뉴클레오티드내에서) 발생하는 것이 바람직하다. 일 실시형태에서, 센스 및 안티센스 가닥으로부터 형성된 이중체 영역에서 임의의 미스매치는 안티센스 가닥의 5' 말단의 6, 5, 4, 3, 2, 또는 1개의 뉴클레오티드 내에서 발생한다.
특정 실시형태에서, 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 실시형태에서, 본 발명의 RNAi 작제물은 siRNA를 포함한다.
dsRNA의 2개의 실질적으로 상보적인 가닥이 별도의 RNA 분자로 구성되는 경우, 이들 분자는 공유적으로 연결될 필요는 없으나, 공유적으로 연결될 수 있다. 두 가닥이 하나의 가닥의 3'-말단과 이중체 구조를 형성하는 각각의 다른 가닥의 5'-말단 사이에 중단되지 않은 뉴클레오티드 사슬 이외의 수단에 의해 공유 연결되는 경우, 연결 구조는 "링커"로 지칭된다. RNA 가닥은 동일하거나 상이한 수의 뉴클레오티드를 가질 수 있다. 이중체에서의 염기쌍의 최대 수는 dsRNA의 최단 가닥의 뉴클레오티드 수에서 이중체에 존재하는 임의의 오버행을 뺀 수이다. 이중체 구조 이외에, RNAi는 하나 이상의 뉴클레오티드 오버행을 포함할 수 있다.
다른 실시형태에서, 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"(shRNA)으로 지칭된다. 일부 실시형태에서, 루프 영역은 적어도 1, 2, 3, 4, 5, 10, 20, 또는 25개의 짝없는 뉴클레오티드를 포함할 수 있다. 일부 실시형태에서, 루프 영역은 10, 9, 8, 7, 6, 5, 4, 3, 2개, 또는 그 이하의 짝없는 뉴클레오티드를 가질 수 있다. 특정 실시형태에서, 본 발명의 RNAi 작제물은 shRNA를 포함한다. 단일, 적어도 부분적으로 자기-상보성 RNA 분자의 길이는 약 35개의 뉴클레오티드 내지 약 100개의 뉴클레오티드, 약 45개의 뉴클레오티드 내지 약 85개의 뉴클레오티드, 또는 약 50 내지 약 60개의 뉴클레오티드일 수 있으며, 각각 본원에 인용된 길이를 갖는 이중체 영역 및 루프 영역을 포함한다.
일부 실시형태에서, 본 발명의 RNAi 작제물은 센스 가닥 및 안티센스 가닥을 포함하며, 상기 안티센스 가닥은 PNPLA3 메신저 RNA(mRNA) 서열에 실질적으로 또는 완전히 상보적인 서열을 갖는 영역을 포함한다. 본 명세서에 사용된 바와 같이, "PNPLA3 mRNA 서열"은 PNPLA3 단백질 변이체 또는 임의의 종(예를 들어, 마우스, 래트, 비-인간 영장류, 인간)으로부터의 이소형을 포함하는, PNPLA3 단백질을 암호화하는, 스플라이스 변이체를 포함하는 임의의 메신저 RNA 서열을 지칭한다. PNPLA3 단백질은 또한, 아디포뉴트린(ADPN) 및 칼슘-비의존적 포스포리파제 A2-엡실론(iPLA(2)□)으로도 알려져 있다.
PNPLA3 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 PNPLA3 mRNA 서열 또는 PNPLA3 cDNA 서열에 실질적으로 또는 완전히 상보적인 서열을 갖는 영역을 포함할 수 있다. PNPLA3 mRNA 또는 cDNA 서열은 임의의 PNPLA3 mRNA 또는 cDNA 서열을 포함할 수 있지만, 이에 제한되지 않으며, 예컨대 NCBI 참조 서열 Nm_025225.2로부터 유래될 수 있다.
안티센스 가닥의 영역은 PNPLA3 mRNA 서열의 적어도 15개의 연속 뉴클레오티드에 실질적으로 상보적이거나 완전히 상보적일 수 있다. 일부 실시형태에서, 안티센스 가닥이 상보성 영역을 포함하는 PNPLA3 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 25개의 연속 뉴클레오티드, 약 19 내지 약 23개의 연속 뉴클레오티드, 또는 약 19 내지 약 21개의 연속 뉴클레오티드의 범위일 수 있다. 특정 실시형태에서, PNPLA3 mRNA 서열에 실질적으로 또는 완전히 상보적인 서열을 포함하는 안티센스 가닥의 영역은 일부 실시형태에서, 표 1 또는 표 2에 열거된 안티센스 서열로부터의 적어도 15개의 인접 뉴클레오티드를 포함할 수 있다. 다른 실시형태에서, 안티센스 서열은 표 1 또는 표 2에 열거된 안티센스 서열로부터의 적어도 16개, 적어도 17개, 적어도 18개, 또는 적어도 19개의 인접 뉴클레오티드를 포함한다. 일부 실시형태에서, 센스 및/또는 안티센스 서열은 1, 2, 또는 3개 이하의 뉴클레오티드 미스매치를 갖는, 표 1 또는 2에 열거된 서열로부터의 적어도 15개의 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 실시형태에서, 이중체 영역은 길이가 약 15 내지 약 30개의 염기쌍이다. 이 범위 내의 이중체 영역에 대한 다른 길이도 또한 적합하며, 예컨대 약 15 내지 약 28개의 염기쌍, 약 15 내지 약 26개의 염기쌍, 약 15 내지 약 24개의 염기쌍, 약 15 내지 약 22개의 염기쌍, 약 17 내지 약 28개의 염기쌍, 약 17 내지 약 26개의 염기쌍, 약 17 내지 약 24개의 염기쌍, 약 17 내지 약 23개의 염기쌍, 약 17 내지 약 21개의 염기쌍, 약 19 내지 약 25개의 염기쌍, 약 19 내지 약 23개의 염기쌍, 또는 약 19 내지 약 21개의 염기쌍이다. 일 실시형태에서, 이중체 영역은 길이가 약 17 내지 약 24개의 염기쌍이다. 또 다른 실시형태에서, 이중체 영역은 길이가 약 19 내지 약 21개의 염기쌍이다.
일부 실시형태에서, 본 발명의 RNAi 작용제는 표적 RNA의 절단을 지시하기 위해 표적 RNA 서열, 예를 들어, PNPLA3 표적 mRNA 서열과 상호작용하는 약 24 내지 약 30개의 뉴클레오티드의 이중체 영역을 함유한다. 이론에 얽메이지 않고, 세포에 도입된 긴 이중 가닥 RNA는 다이서로 알려진 유형 III 엔도뉴클레아제에 의해 siRNA로 분해될 수 있다(Sharp et al. (2001) Genes Dev. 15:485). 리보뉴클레아제-III-유사 효소인, 다이서, 15는 dsRNA를 특징적인 2개의 염기 3' 오버행을 갖는 19~23개의 염기쌍의 짧은 간섭 RNA로 처리한다(Bernstein, et al., (2001) Nature 409:363). 그런 다음 siRNA는 하나 이상의 헬리카제가 siRNA 이중체를 풀고, 상보적인 안티센스 가닥이 표적 인식을 안내할 수 있게 하는 RNA-유도 사일런싱 복합체(RISC)에 통합된다(Nykanen, et al., (2001) Cell107:309). 적당한 표적 20 mRNA에 결합시, RISC 내의 하나 이상의 엔도뉴클레아제는 표적을 절단하여 사일런싱을 유도한다(Elbashir, et al., (2001) Genes Dev. 15: 188).
센스 가닥 및 안티센스 가닥이 2개의 별개의 분자(예를 들어, RNAi 작제물이 siRNA를 포함함)인 실시형태의 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 실시형태에서, RNAi 작제물은 적어도 하나의 뉴클레오티드 오버행을 포함한다. 본 명세서에 사용된 바와 같이, "뉴클레오티드 오버행"은 가닥의 말단에서 이중체 영역을 넘어 연장되는 짝없는 뉴클레오티드 또는 뉴클레오티드들을 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 오버행의 길이는 일반적으로 1 내지 6개의 뉴클레오티드, 1 내지 5개의 뉴클레오티드, 1 내지 4개의 뉴클레오티드, 1 내지 3개의 뉴클레오티드, 2 내지 6개의 뉴클레오티드, 2 내지 5개의 뉴클레오티드, 또는 2 내지 4개의 뉴클레오티드이다. 일부 실시형태에서, 뉴클레오티드 오버행은 1, 2, 3, 4, 5, 또는 6개의 뉴클레오티드를 포함한다. 하나의 특정 실시형태에서, 뉴클레오티드 오버행은 1 내지 4개의 뉴클레오티드를 포함한다. 특정 실시형태에서, 뉴클레오티드 오버행은 2개의 뉴클레오티드를 포함한다. 오버행 내의 뉴클레오티드는 본원에 기재된 리보뉴클레오티드, 데옥시리보뉴클레오티드, 또는 변형된 뉴클레오티드일 수 있다. 일부 실시형태에서, 오버행은 5'-우리딘우리딘-3'(5'-UU-3') 디뉴클레오티드를 포함한다. 상기 실시형태에서, UU 디뉴클레오티드는 리보뉴클레오티드 또는 변형된 뉴클레오티드, 예를 들어, 2'-변형된 뉴클레오티드를 포함할 수 있다. 다른 실시형태에서, 오버행은 5'-데옥시티미딘-데옥시티미딘-3'(5'-dTdT-3') 디뉴클레오티드를 포함한다.
뉴클레오티드 오버행은 하나 또는 양쪽 모두의 가닥의 5' 말단 또는 3' 말단에 있을 수 있다. 예를 들어, 일 실시형태에서, RNAi 작제물은 안티센스 가닥의 5' 말단 및 3' 말단에 뉴클레오티드 오버행을 포함한다. 또 다른 실시형태에서, RNAi 작제물은 센스 가닥의 5' 말단 및 3' 말단에 뉴클레오티드 오버행을 포함한다. 일부 실시형태에서, RNAi 작제물은 센스 가닥의 5' 말단 및 안티센스 가닥의 5' 말단에 뉴클레오티드 오버행을 포함한다. 다른 실시형태에서, 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 실시형태에서, RNAi 작제물은 센스 가닥의 3' 말단에 뉴클레오티드 오버행을 포함하고, 센스 가닥의 5' 말단 및 안티센스 가닥의 3' 말단에 평활 말단을 포함한다. 다른 실시형태에서, RNAi 작제물은 안티센스 가닥의 3' 말단에 뉴클레오티드 오버행을 포함하고, 안티센스 가닥의 5' 말단 및 센스 가닥의 3' 말단에 평활 말단을 포함한다. 특정 실시형태에서, RNAi 작제물은 이중-가닥 RNA 분자의 양쪽 말단에 평활 말단을 포함한다. 상기 실시형태에서, 센스 가닥 및 안티센스 가닥은 길이가 동일하고, 이중체 영역은 센스 및 안티센스 가닥과 길이가 동일하다(즉, 분자는 전체 길이에 걸쳐 이중 가닥임).
센스 가닥 및 안티센스 가닥은 각각 독립적으로 약 15 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 21 내지 약 25개 뉴클레오티드 길이, 또는 약 21 내지 약 23개 뉴클레오티드 길이일 수 있다. 특정 실시형태에서, 센스 가닥 및 안티센스 가닥은 각각 약 18, 약 19, 약 20, 약 21, 약 22, 약 23, 약 24, 또는 약 25개 뉴클레오티드 길이이다. 일부 실시형태에서, 센스 가닥 및 안티센스 가닥은 길이가 동일하지만, RNAi 작제물이 2개의 뉴클레오티드 오버행을 갖도록 가닥보다 짧은 이중체 영역을 형성한다. 예를 들어, 일 실시형태에서, 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 모두에서 2개의 짝없는 뉴클레오티드의 뉴클레오티드 오버행을 포함한다. 또 다른 실시형태에서, 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 모두에서 2개의 짝없는 뉴클레오티드의 뉴클레오티드 오버행을 포함한다. 다른 실시형태에서, 센스 가닥 및 안티센스 가닥은 동일한 길이를 가지며, 이중-가닥 분자의 양쪽 말단에 뉴클레오티드 오버행이 없도록 전체 길이에 걸쳐 이중체 영역을 형성한다. 하나의 이러한 실시형태에서, RNAi 작제물은 평활 말단이며, (i) 각각 21개의 뉴클레오티드 길이인, 센스 가닥 및 안티센스 가닥, 및 (ii) 21개 염기쌍 길이의 이중체 영역을 포함한다. 또 다른 이러한 실시형태에서, RNAi 작제물은 평활 말단이며, (i) 각각 23개의 뉴클레오티드 길이인, 센스 가닥 및 안티센스 가닥, 및 (ii) 23개의 염기쌍 길이의 이중체 영역을 포함한다.
다른 실시형태에서, 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 실시형태에서, RNAi 작제물은 (i) 19개의 뉴클레오티드 길이인, 센스 가닥, (ii) 21개의 뉴클레오티드 길이인, 안티센스 가닥, (iii) 19개의 염기쌍 길이의 이중체 영역, 및 (iv) 안티센스 가닥의 3' 말단에서 2개의 짝없는 뉴클레오티드의 단일 뉴클레오티드 오버행을 포함한다. 또 다른 실시형태에서, RNAi 작제물은 (i) 21개의 뉴클레오티드 길이인, 센스 가닥, (ii) 23개의 뉴클레오티드 길이인, 안티센스 가닥, (iii) 21개의 염기쌍 길이의 이중체 영역, 및 (iv) 안티센스 가닥의 3' 말단에서 2개의 짝없는 뉴클레오티드의 단일 뉴클레오티드 오버행을 포함한다.
본 발명의 RNAi 작제물의 안티센스 가닥은 표 1 또는 표 2에 열거된 안티센스 서열 또는 상기 안티센스 서열 중 임의의 것의 뉴클레오티드 1~19의 서열 중 어느 하나의 서열을 포함할 수 있다.
표 1 및 6에 열거된 각각의 안티센스 서열은 PNPLA3 mRNA 서열에 더하여 2개의 뉴클레오티드 오버행 서열에 상보적인 19개의 연속 뉴클레오티드의 서열(5' 말단으로부터 계수된 처음 19개의 뉴클레오티드)을 포함한다. 따라서, 일부 실시형태에서, 안티센스 가닥은 서열 번호: 1~166 또는 167~332 중 어느 하나의 뉴클레오티드 1~19의 서열을 포함한다.
변형된 뉴클레오티드
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. 본 명세서에 사용된 바와 같이, 변형된 뉴클레오티드는 아데노신 모노포스페이트, 구아노신 모노포스페이트, 우리딘 모노포스페이트, 및 시티딘 모노포스페이트를 함유하는 리보뉴클레오티드, 및 데옥시아데노신 모노포스페이트, 데옥시구아노신 모노포스페이트, 데옥시티미딘 모노포스페이트, 및 데옥시시티딘 모노포스페이트를 함유하는 데옥시리보뉴클레오티드를 포함하지 않는다. 그러나, RNAi 작제물은 변형된 뉴클레오티드, 리보뉴클레오티드, 및 데옥시리보뉴클레오티드의 조합을 포함할 수 있다. 변형된 뉴클레오티드를 이중-가닥 RNA 분자의 하나 또는 양쪽 가닥에 통합하면, 예를 들어, 뉴클레아제 및 다른 분해 과정에 대한 분자의 민감성을 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 실시형태에서, 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 H 또는 OH 이외의 2' 위치에 치환기를 갖는 펜토스 고리를 갖는 뉴클레오티드를 지칭한다. 이러한 2' 변형은 2'-O-알킬(예를 들어, O-C1-C10 또는 O-C1-C10 치환된 알킬), 2'-O-알릴 (O-CH2CH=CH2), 2'-C-알릴, 2'-플루오로, 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); 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 실시형태에서, 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 □-L-메틸렌옥시 (4'-CH2-O-2') 이환식 핵산 (BNA); □-D-메틸렌옥시 (4'-CH2-O-2') BNA (잠긴 핵산 또는 LNA로도 지칭됨); 에틸렌옥시 (4'-(CH2)2-O-2') BNA; 아미노옥시 (4'-CH2-O-N(R)- 2')BNA; 옥시아미노 (4'-CH2-N(R)-O-2') BNA; 메틸(메틸렌옥시) (4'-CH(CH3)-O-2') BNA (제한된 에틸 또는 cEt로도 지칭됨); 메틸렌-티오 (4'-CH2-S-2') BNA; 메틸렌-아미노 (4'-CH2-N(R)-2') BNA; 메틸 카르보사이클릭 (4'-CH2-CH(CH3)-2') BNA; 프로필렌 카르보사이클릭 (4'-(CH2)3-2') BNA; 및 메톡시(에틸렌옥시) (4'-CH(CH2OMe)-O-2')BNA (제한된 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 본 명세서에 참고로 포함된다.
일부 실시형태에서, RNAi 작제물은 하나 이상의 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, 이환식 핵산(BNA), 또는 이들의 조합을 포함한다. 특정 실시형태에서, RNAi 작제물은 하나 이상의 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 또는 이들의 조합을 포함한다. 하나의 특정 실시형태에서, RNAi 작제물은 하나 이상의 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드 또는 이들의 조합을 포함한다.
RNAi 작제물의 센스 및 안티센스 가닥 둘다는 1개 또는 다수의 변형된 뉴클레오티드를 포함할 수 있다. 예를 들어, 일부 실시형태에서, 센스 가닥은 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 또는 그 이상의 변형된 뉴클레오티드를 포함한다. 특정 실시형태에서, 센스 가닥내 모든 뉴클레오티드는 변형된 뉴클레오티드이다. 일부 실시형태에서, 안티센스 가닥은 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 또는 그 이상의 변형된 뉴클레오티드를 포함한다. 다른 실시형태에서, 안티센스 가닥내 모든 뉴클레오티드는 변형된 뉴클레오티드이다. 특정 다른 실시형태에서, 센스 가닥내 모든 뉴클레오티드 및 안티센스 가닥내 모든 뉴클레오티드는 변형된 뉴클레오티드이다. 이들 및 다른 실시형태에서, 변형된 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 또는 이들의 조합일 수 있다.
일부 실시형태에서, 센스 가닥, 안티센스 가닥, 또는 양쪽 가닥에서 아데노신 뉴클레오티드 앞의 모든 피리미딘 뉴클레오티드는 변형된 뉴클레오티드이다. 예를 들어, 서열 5'-CA-3' 또는 5'-UA-3'이 가닥 중 어느 하나에 나타나는 경우, 시티딘 및 우리딘 뉴클레오티드는 변형된 뉴클레오티드, 바람직하게 2'-O-메틸 변형된 뉴클레오티드이다. 특정 실시형태에서, 센스 가닥내 모든 피리미딘 뉴클레오티드는 변형된 뉴클레오티드 (예를 들어, 2'-O-메틸 변형된 뉴클레오티드)이며, 안티센스 가닥에서 서열 5'-CA-3' 또는 5'-UA-3'의 모든 경우에 5' 뉴클레오티드는 변형된 뉴클레오티드 (예를 들어, 2'-O-메틸 변형된 뉴클레오티드)이다. 다른 실시형태에서, 이중체 영역의 모든 뉴클레오티드는 변형된 뉴클레오티드이다. 상기 실시형태에서, 변형된 뉴클레오티드는 바람직하게 2'-O-메틸 변형된 뉴클레오티드, 2'-플루오로 변형된 뉴클레오티드 또는 이들의 조합이다.
RNAi 작제물이 뉴클레오티드 오버행을 포함하는 실시형태에서, 오버행의 뉴클레오티드는 리보뉴클레오티드, 데옥시리보뉴클레오티드, 또는 변형된 뉴클레오티드일 수 있다. 일 실시형태에서, 오버행의 뉴클레오티드는 데옥시리보뉴클레오티드, 예를 들어, 데옥시티미딘이다. 또 다른 실시형태에서, 오버행의 뉴클레오티드는 변형된 뉴클레오티드이다. 예를 들어, 일부 실시형태에서, 오버행의 뉴클레오티드는 2'-O-메틸 변형된 뉴클레오티드, 2'-플루오로 변형된 뉴클레오티드, 2'-메톡시에틸 변형된 뉴클레오티드, 또는 이들의 조합이다.
본 발명의 RNAi 작제물은 또한, 하나 이상의 변형된 뉴클레오티드간 연결을 포함할 수 있다. 본 명세서에 사용된 바와 같이, 용어 "변형된 뉴클레오티드간 연결"은 천연 3' 내지 5' 포스포디에스테르 연결 이외의 뉴클레오티드간 연결을 지칭한다. 일부 실시형태에서, 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 (P=S), 키랄포스포로티오에이트, 포스포로디티오에이트, 티오노포스포라미데이트, 티오노알킬포스포네이트, 티오노알킬포스포트리에스테르, 및 보라노포스페이트이다. 일 실시형태에서, 변형된 뉴클레오티드간 연결은 2' 내지 5' 포스포디에스테르 연결이다. 다른 실시형태에서, 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 실시형태에서, 변형된 뉴클레오시드간 연결은 펩타이드 핵산 또는 PNA, 예컨대 미국 특허 제5,539,082호; 제5,714,331호; 및 제5,719,262호에 기재된 것들을 생성하기 위한 펩타이드-기반 연결(예를 들어, 아미노에틸글리신)이다. 다른 적당한 변형된 뉴클레오티드간 및 본 발명의 RNAi 작제물에 사용될 수 있는 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 본 명세서에 참고로 포함된다.
특정 실시형태에서, 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 실시형태에서, 센스 가닥은 1, 2, 3, 4, 5, 6, 7, 8개, 또는 그 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 다른 실시형태에서, 안티센스 가닥은 1, 2, 3, 4, 5, 6, 7, 8개, 또는 그 이상의 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 또 다른 실시형태에서, 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 실시형태에서, 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 실시형태에서, RNAi 작제물은 센스 가닥, 안티센스 가닥, 또는 양쪽 가닥의 5'-말단에 약 1 내지 약 6개 또는 그 이상의 (예를 들어, 약 1, 2, 5, 4, 5, 6개 또는 그 이상의) 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 일 실시형태에서, RNAi 작제물은 센스 가닥의 3' 말단에 단일 포스포로티오에이트 뉴클레오티드간 연결 및 안티센스 가닥의 3' 말단에 단일 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 또 다른 실시형태에서, RNAi 작제물은 안티센스 가닥의 3' 말단에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결(즉, 안티센스 가닥의 3' 말단에서의 제1 및 제2 뉴클레오티드간 연결에 포스포로티오에이트 뉴클레오티드간 연결)을 포함한다. 또 다른 실시형태에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 양쪽에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 또 다른 실시형태에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 양쪽에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결 및 센스 가닥의 5' 말단에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함한다. 또 다른 실시형태에서, RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 양쪽에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을, 및 센스 가닥의 3' 및 5' 말단 양쪽에 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. 하나 또는 둘 모두의 가닥이 하나 이상의 포스포로티오에이트 뉴클레오티드 간 연결을 포함하는 임의의 실시형태에서, 가닥 내의 나머지 뉴클레오티드간 연결은 천연 3' 내지 5' 포스포디에스테르 연결일 수 있다. 예를 들어, 일부 실시형태에서, 센스 및 안티센스 가닥의 각각의 뉴클레오티드간 연결은 포스포디에스테르 및 포스포로티오에이트로부터 선택되며, 여기서 적어도 하나의 뉴클레오티드간 연결은 포스포로티오에이트이다.
RNAi 작제물이 뉴클레오티드 오버행을 포함하는 실시형태에서, 오버행에서의 2개 이상의 짝없는 뉴클레오티드가 포스포로티오에이트 뉴클레오티드간 연결에 의해 연결될 수 있다. 특정 실시형태에서, 안티센스 가닥 및/또는 센스 가닥의 3' 말단에서 뉴클레오티드 오버행 내의 모든 짝없는 뉴클레오티드는 포스포로티오에이트 뉴클레오티드간 연결에 의해 연결된다. 다른 실시형태에서, 안티센스 가닥 및/또는 센스 가닥의 5' 말단에서 뉴클레오티드 오버행 내의 모든 짝없는 뉴클레오티드는 포스포로티오에이트 뉴클레오티드간 연결에 의해 연결된다. 또 다른 실시형태에서, 임의의 뉴클레오티드 오버행에서 모든 짝없는 뉴클레오티드는 포스포로티오에이트 뉴클레오티드간 연결에 의해 연결된다.
특정 실시형태에서, 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 또는 천연 발생 변형일 수 있으며, 유니버셜 염기, 5-메틸시토신(5-me-C), 5-하이드록시메틸 시토신, 잔틴(X), 하이포잔틴(I), 2-아미노아데닌, 아데닌 및 구아닌의 6-메틸아데닌, 6-메틸구아닌 및 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, 이들로 제한되지는 않는다.
일부 실시형태에서, 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. Chern., Vol. 76: 7295-7300, 2011에 기재된 것들을 포함하며, 이들은 둘 다 그 전문이 본 명세서에 참고로 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.
본 발명의 RNAi 작제물의 일부 실시형태에서, 센스 가닥, 안티센스 가닥, 또는 안티센스 및 센스 가닥 둘다의 5' 말단은 포스페이트 모이어티를 포함한다. 본 명세서에 사용된 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 알킬로 대체된 포스페이트를 포함하며, 여기서 R은 H, 아미노 보호 기 또는 치환되지 않은, 또는 치환된 알킬이다. 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'-메틸)을 포함할 수 있으며, 변형된 염기(예를 들어, 5-메틸 시토신 또는 슈도우라실)를 포함할 수 있다. 다른 실시형태에서, 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 실시형태에서, 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 실시형태에서, 본 발명의 RNAi 작제물의 하나 또는 둘 모두의 가닥은 2' 변형된 뉴클레오티드 또는 BNA 및 포스포로티오에이트 뉴클레오티드간 연결의 조합을 포함한다. 특정 실시형태에서, 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.
RNAi 작제물의 기능
바람직하게는, 본 발명의 RNAi 작제물은 세포, 특히 간 세포에서 PNPLA3의 발현을 감소시키거나 억제한다. 따라서, 일 실시형태에서, 본 발명은 세포를 본원에 기재된 임의의 RNAi 작제물과 접촉시킴으로써 세포에서 PNPLA3 발현을 감소시키는 방법을 제공한다. 세포는 시험관내 또는 생체내에 있을 수 있다. PNPLA3 발현은 PNPLA3 mRNA, PNPLA3 단백질, 또는 PNPLA3 발현에 연결된 또 다른 바이오마커의 양 또는 수준을 측정함으로써 평가될 수 있다. 본 발명의 RNAi 작제물로 처리된 세포 또는 동물에서 PNPLA3 발현의 감소는 RNAi 작제물로 처리되지 않거나 대조군 RNAi 작제물로 처리된 세포 또는 동물에서의 PNPLA3 발현과 관련하여 결정될 수 있다. 예를 들어, 일부 실시형태에서, PNPLA3 발현의 감소는 (a) 본 발명의 RNAi 작제물로 처리된 간 세포에서 PNPLA3 mRNA의 양 또는 수준을 측정하고, (b) 대조군 RNAi 작제물(예를 들어, 간 세포에서 발현되지 않는 RNA 분자 또는 논센스 또는 스크램블링된 서열을 갖는 RNAi 작제물을 지향하는 RNAi 작용제)로 처리되거나 작제물이 없는 간 세포내 PNPLA3 mRNA의 양 또는 수준을 측정하고, 및 (c) (a)에서의 처리된 세포로부터 측정된 PNPLA3 mRNA 수준을 (b)에서의 대조군 세포로부터 측정된 PNPLA3 mRNA 수준과 비교함으로써 평가된다. 처리된 세포 및 대조군 세포에서의 PNPLA3 mRNA 수준은 비교 전에 대조군 유전자 유전자(예를 들어, 18S 리보솜 RNA)에 대한 RNA 수준으로 정규화될 수 있다. PNPLA3 mRNA 수준은 노던 블롯 분석, 뉴클레아제 보호 분석, 형광성 인시추 하이브리드화(FISH), 역전사 효소(RT)-PCR, 실시간 RT-PCR, 정량적 PCR 등을 포함하는 다양한 방법으로 측정될 수 있다.
다른 실시형태에서, PNPLA3 발현의 감소는 (a) 본 발명의 RNAi 작제물로 처리된 간 세포에서 PNPLA3 단백질의 양 또는 수준을 측정하고, (b) 대조군 RNAi 작제물(예를 들어, 간 세포에서 발현되지 않는 RNA 분자 또는 논센스 또는 스크램블링된 서열을 갖는 RNAi 작제물을 지향하는 RNAi 작용제)로 처리되거나 작제물이 없는 간 세포내 PNPLA3 단백질의 양 또는 수준을 측정하고, 및 (c) (a)에서의 처리된 세포로부터 측정된 PNPLA3 단백질 수준을 (b)에서의 대조군 세포로부터 측정된 PNPLA3 단백질 수준과 비교함으로써 평가된다. PNPLA3 단백질 수준을 측정하는 방법은 당업자에게 공지되어 있으며, 웨스턴 블롯, 면역 분석(예를 들어, ELISA), 및 유세포 분석을 포함한다. PNPLA3 단백질 발현을 평가하기 위한 예시적인 면역분석-기반 방법은 실시예 2에 기재되어 있다. 실시예 3은 RNA FISH를 사용하여 PNPLA3 mRNA를 측정하는 예시적인 방법을 기술한다. PNPLA3 mRNA 또는 단백질을 측정할 수 있는 임의의 방법을 사용하여 본 발명의 RNAi 작제물의 효능을 평가할 수 있다.
일부 실시형태에서, PNPLA3 발현 수준을 평가하는 방법은 PNPLA3를 본래 발현하는 세포(예를 들어, 간 세포) 또는 PNPLA3을 발현하도록 조작된 세포에서 시험관 내에서 수행된다. 특정 실시형태에서, 방법은 간 세포에서 시험관내 수행된다. 적합한 간 세포는 1차 간세포(예를 들어, 인간, 비-인간 영장류 또는 설치류 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 실시형태에서, 간 세포는 Hep3B 세포이다. 또 다른 실시형태에서, 간 세포는 HepG2 세포이다.
다른 실시형태에서, PNPLA3 발현 수준을 평가하는 방법은 생체내에서 수행된다. RNAi 작제물 및 임의의 대조군 RNAi 작제물은 동물(예를 들어, 설치류 또는 비-인간 영장류)에 투여될 수 있고, 치료 후 동물로부터 수확된 간 조직에서 평가된 PNPLA3 mRNA 또는 단백질 수준으로 투여될 수 있다. 대안적으로 또는 추가적으로, PNPLA3 발현과 관련된 바이오마커 또는 기능적 표현형은 처리된 동물에서 평가될 수 있다.
특정 실시형태에서, PNPLA3의 발현은 간 세포에서 본 발명의 RNAi 작제물에 의해 적어도 10%, 적어도 15%, 적어도 20%, 적어도 25%, 적어도 30%, 적어도 35%, 적어도 40%, 적어도 45%, 또는 적어도 50% 감소된다. 일부 실시형태에서, PNPLA3의 발현은 간 세포에서 본 발명의 RNAi 작제물에 의해 적어도 60%, 적어도 65%, 적어도 70%, 적어도 75%, 적어도 80%, 또는 적어도 85% 감소된다. 다른 실시형태에서, PNPLA3의 발현은 간 세포에서 본 발명의 RNAi 작제물에 의해 약 90% 이상, 예를 들어, 91%, 92%, 93%, 94%, 95%, 96%,97%, 98%, 99%, 또는 그 이상 감소된다. PNPLA3 발현의 감소 백분율은 본원에 기재된 임의의 방법뿐만 아니라 당 업계에 공지된 다른 방법에 의해 측정될 수 있다. 예를 들어, 특정 실시형태에서, 본 발명의 RNAi 작제물은 시험관내 Hep3B 세포(야생형 PNPLA3을 함유함)에서 5 nM으로 PNPLA3 발현의 적어도 45%를 억제한다. 관련 실시형태에서, 본 발명의 RNAi 작제물은 시험관내 Hep3B 세포에서 5 nM으로 PNPLA3 발현의 적어도 50%, 적어도 55%, 적어도 60%, 적어도 65%, 적어도 70%, 또는 적어도 75%를 억제한다. 다른 실시형태에서, 본 발명의 RNAi 작제물은 시험관내 Hep3B 세포에서 5 nM으로 PNPLA3 발현의 적어도 80%, 적어도 85%, 적어도 90%, 적어도 92%, 적어도 94%, 적어도 96%, 또는 적어도 98%를 억제한다. 특정 실시형태에서, 본 발명의 RNAi 작제물은 시험관내 HepG2 세포(PNPLA3-rs738409-rs738408 이중 소수 대립유전자를 함유함)에서 5 nM으로 PNPLA3 발현의 적어도 45%를 억제한다. 관련 실시형태에서, 본 발명의 RNAi 작제물은 시험관내 HepG2 세포에서 5 nM으로 PNPLA3 발현의 적어도 50%, 적어도 55%, 적어도 60%, 적어도 65%, 적어도 70%, 또는 적어도 75%를 억제한다. 다른 실시형태에서, 본 발명의 RNAi 작제물은 시험관내 HepG2 세포에서 5 nM으로 PNPLA3 발현의 적어도 80%, 적어도 85%, 적어도 90%, 적어도 92%, 적어도 94%, 적어도 96%, 또는 적어도 98%를 억제한다. 특정 실시형태에서, 본 발명의 RNAi 작제물은 인간 PNPLA3 I148I를 발현하는 CHO 트랜스펙션된 세포 또는 시험관내 I148M 세포에서 5 nM으로 PNPLA3 발현의 적어도 45%를 억제한다. 관련 실시형태에서, 본 발명의 RNAi 작제물은 시험관내에서 인간 PNPLA3 I148I 또는 I148M을 발현하는 CHO 트랜스펙션된 세포에서 5 nM으로 PNPLA3 발현의 적어도 50%, 적어도 55%, 적어도 60%, 적어도 65%, 적어도 70%, 또는 적어도 75%를 억제한다. 다른 실시형태에서, 본 발명의 RNAi 작제물은 시험관내에서 인간 PNPLA3 I148I 또는 I148M을 발현하는 CHO 트랜스펙션된 세포에서 5 nM으로 PNPLA3 발현의 적어도 80%, 적어도 85%, 적어도 90%, 적어도 92%, 적어도 94%, 적어도 96%, 또는 적어도 98%를 억제한다. PNPLA3의 감소는 실시예 2 및 3에 기재된 바와 같이 RNA FISH 또는 액적 디지털 PCR을 포함하는 다양한 기술을 사용하여 측정될 수 있다.
일부 실시형태에서, 간 세포에서 PNPLA3 발현을 억제하기 위한 본 발명의 RNAi 작제물의 효능을 평가하기 위해 IC50 값이 계산된다. "IC50 값"은 생물학적 또는 생화학적 기능의 50% 저해를 달성하는 데 필요한 용량/농도이다. 임의의 특정 물질 또는 길항제에 대한 IC50 값은 용량-반응 곡선을 구성하고 임의의 분석에서 발현 수준 또는 기능적 활성에 대한 물질 또는 길항제의 상이한 농도의 효과를 조사함으로써 결정될 수 있다. IC50 값은 최대 생물학적 반응 또는 자연 발현 수준의 절반을 저해하는 데 필요한 농도를 결정함으로써 주어진 길항제 또는 물질에 대해 계산될 수 있다. 따라서, 임의의 RNAi 작제물에 대한 IC50 값은 임의의 분석, 예컨대 실시예에 기재된 면역분석 또는 RNA FISH 분석 또는 액적 디지털 PCR 분석에서 간 세포 내 천연 PNPLA3 발현 수준(예를 들어, 대조군 간 세포 내 PNPLA3 발현 수준)의 절반을 억제하는데 필요한 RNAi 작제물의 농도를 결정함으로써 계산될 수 있다. 본 발명의 RNAi 작제물은 약 20 nM 미만의 IC50으로 간 세포(예를 들어, Hep3B 세포)에서 PNPLA3 발현을 억제할 수 있다. 예를 들어, RNAi 작제물은 약 0.001 nM 내지 약 20 nM, 약 0.001 nM 내지 약 10 nM, 약 0.001 nM 내지 약 5 nM, 약 0.001 nM 내지 약 1 nM, 약 0.1 nM 내지 약 10 nM, 약 0.1 nM 내지 약 5 nM, 또는 약 0.1 nM 내지 약 1 nM의 IC50으로 간 세포에서 PNPLA3 발현을 억제한다. 특정 실시형태에서, RNAi 작제물은 약 1 nM 내지 약 10 nM의 IC50으로 간 세포(예를 들어, Hep3B 세포)에서 PNPLA3 발현을 억제한다. 본 발명의 RNAi 작제물은 약 20 nM 미만의 IC50으로 간 세포(예를 들어, HepG2 세포)에서 PNPLA3 발현을 억제할 수 있다. 예를 들어, RNAi 작제물은 약 0.001 nM 내지 약 20 nM, 약 0.001 nM 내지 약 10 nM, 약 0.001 nM 내지 약 5 nM, 약 0.001 nM 내지 약 1 nM, 약 0.1 nM 내지 약 10 nM, 약 0.1 nM 내지 약 5 nM, 또는 약 0.1 nM 내지 약 1 nM의 IC50으로 간 세포에서 PNPLA3 발현을 억제한다. 특정 실시형태에서, RNAi 작제물은 약 1 nM 내지 약 10 nM의 IC50으로 간 세포(예를 들어, HepG2 세포)에서 PNPLA3 발현을 억제한다. 본 발명의 RNAi 작제물은 약 20 nM 미만의 IC50으로 간 세포(예를 들어, 인간 PNPLA3 I148I 또는 I148M을 발현하는 CHO 트랜스펙션된 세포)에서 PNPLA3 발현을 억제할 수 있다. 예를 들어, RNAi 작제물은 약 0.001 nM 내지 약 20 nM, 약 0.001 nM 내지 약 10 nM, 약 0.001 nM 내지 약 5 nM, 약 0.001 nM 내지 약 1 nM, 약 0.1 nM 내지 약 10 nM, 약 0.1 nM 내지 약 5 nM, 또는 약 0.1 nM 내지 약 1 nM의 IC50으로 간 세포에서 PNPLA3 발현을 억제한다. 특정 실시형태에서, RNAi 작제물은 약 1 nM 내지 약 10 nM의 IC50으로 간 세포(예를 들어, 인간 PNPLA3 I148I 또는 I148M을 발현하는 CHO 트랜스펙션된 세포)에서 PNPLA3 발현을 억제한다.
본 발명의 RNAi 작제물은 당 업계에 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.
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. 바람직한 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. 포스 포트리에스테르 또는 포스파이트 트리에스테르의 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 플루오라이드 탈보호 단계에서 용이하게 제거되어 최소 RNA 분해를 초래할 수 있다.
테트라졸 촉매는 표준 포스포라미다이트 커플링 반응에 사용될 수 있다. 바람직한 촉매는 예를 들어, 테트라졸, S-에틸-테트라졸, 벤질티오테트라졸, 프니트로페닐테트라졸을 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 탈보호)은 당 업계에 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); 및 L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995)]에 기재된 것들을 포함하며, 후속 버전의 RNAi 작용제의 맞춤형 합성은 또한 Dharmacon, Inc. (Lafayette, CO), AxoLabs GmbH (Kulmbach, Germany),및 Ambion, Inc.(Foster City, CA)를 포함한 여러 상용 공급 업체로부터 구할 수 있다.
본 발명의 RNAi 작제물은 리간드를 포함할 수 있다. 본 명세서에 사용된 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 단지 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, 콜린산), 지방산(예를 들어, 팔미트산, 미리스트산), 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-비스O(헥사데실)글리세롤, 제라닐옥시헥실기, 헥사데실글리세롤, 보르네올, 멘톨, 1,3-프로판디올, 헵타데실기, 03-(올레오일)리토콜산, 03-(올레오일)콜레산, 디메톡시트리틸 또는 페녹사진), 펩타이드(예를 들어, 안테나피디아 펩타이드, Tat 펩타이드, RGD펩타이드), 알킬화제, 중합체, 예컨대 폴리에틸렌 글리콜(PEG)(예를 들어, PEG-40K), 폴리아미노산, 및 폴리아민(예를 들어, 스페르민, 스페르미딘)을 포함한다.
특정 실시형태에서, 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 펩티도미메틱(peptidomimetic)일 수 있다. 일 실시형태에서, 엔도좀분해 리간드는 엔도좀 pH에서 이의 활성 입체형태를 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(Subbarao et al., Biochemistry, Vol. 26: 2964-2972, 1987), EALA 펩타이드(Vogel et al., J. Am. Chern. Soc.,Vol. 118: 1581-1586, 1996), 및 이들의 유도체(Turk et al., Biochem. Biophys. Acta, Vol.1559: 56-68, 2002)를 포함한다. 일 실시형태에서, 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 실시형태에서, 리간드는 지질 또는 다른 소수성 분자를 포함한다. 일 실시형태에서, 리간드는 콜레스테롤 모이어티 또는 다른 스테로이드를 포함한다. 콜레스테롤 접합된 올리고뉴클레오티드는 이들의 비접합된 카운터파트보다 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. 또 다른 실시형태에서, 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.
PNPLA3이 간 세포(liver cell)(예를 들어, 간세포(hepatocyte))에서 발현되는 것을 고려하면, 특정 실시형태에서, RNAi 작제물을 이들 간 세포에 특이적으로 전달하는 것이 바람직하다. 일부 실시형태에서, RNAi 작제물은 간 세포 표면에 발현된 단백질에 결합하거나 이와 상호작용하는 리간드를 사용함으로써 간을 특이적으로 표적화할 수 있다. 예를 들어, 특정 실시형태에서, 리간드는 간세포상에서 발현된 수용체에 특이적으로 결합하는 항원 결합 단백질(예를 들어, 항체 또는 이의 결합 단편(예를 들어, Fab, scFv))을 포함할 수 있다.
특정 실시형태에서, 리간드는 탄수화물을 포함한다. "탄수화물"은 각각의 탄소 원자에 결합된 산소, 질소 또는 황 원자를 갖는 적어도 6개의 탄소 원자(선형, 분지형 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 실시형태에서, 리간드에 혼입된 탄수화물은 펜토스, 헥소오스, 또는 헵토스로부터 선택된 단당류 및 이러한 단당류 단위를 포함하는 이당류 및 삼당류이다. 다른 실시형태에서, 리간드에 혼입된 탄수화물은 아미노 당, 예컨대 갈락토사민, 글루코사민, N-아세틸갈락토사민, 및 N-아세틸글루코사민이다.
일부 실시형태에서, 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 실시형태에서, 리간드는 글루코스, 갈락토스, 갈락토사민, 또는 글루코사민을 포함한다. 일 실시형태에서, 리간드는 글루코스, 글루코사민, 또는 N-아세틸글루코사민을 포함한다. 또 다른 실시형태에서, 리간드는 갈락토스, 갈락토사민, 또는 N-아세틸-갈락토사민을 포함한다. 특정 실시형태에서, 리간드는 N-아세틸-갈락토사민을 포함한다. 글루코스, 갈락토스, 및 N-아세틸-갈락토사민(GalNAc)을 포함하는 리간드는 화합물을 간 세포로 표적화하는데 특히 효과적이다. 예를 들어, D'Souza and Devarajan, J. Control Release, Vol. 203: 126-139, 2015를 참고한다. 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 실시형태에서, 리간드는 다가 탄수화물 모이어티를 포함한다. 본 명세서에 사용된 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 실시형태에서, 리간드는 다가 갈락토스 모이어티를 포함한다. 다른 실시형태에서, 리간드는 다가 N-아세틸-갈락토사민 모이어티를 포함한다. 이들 및 다른 실시형태에서, 다가 탄수화물 모이어티는 2가, 3가, 또는 4가이다. 상기 실시형태에서, 다가 탄수화물 모이어티는 바이-안테너리(bi-antennary) 또는 트리-안테너리(tri-antennary)일 수 있다. 하나의 특정 실시형태에서, 다가 N-아세틸-갈락토사민 모이어티는 3가 또는 4가이다. 또 다른 특정 실시형태에서, 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 실시형태에서, 리간드는 RNAi 작제물의 센스 또는 안티센스 가닥에 직접 공유적으로 부착된다. 다른 실시형태에서, 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 실시형태에서, 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 실시형태에서, 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 탄소 원자의 예는 2', 3', 및 5' 탄소 원자를 포함한다. 1' 위치는 또한 염기성 잔기와 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.
특정 실시형태에서, 리간드는 센스 또는 안티센스 가닥의 3' 또는 5' 말단에 부착될 수 있다. 특정 실시형태에서, 리간드는 센스 가닥의 5' 말단에 공유적으로 부착된다. 다른 실시형태에서, 리간드는 센스 가닥의 3' 말단에 공유적으로 부착된다. 예를 들어, 일부 실시형태에서, 리간드는 센스 가닥의 3'-말단 뉴클레오티드에 부착된다. 이러한 특정 실시형태에서, 리간드는 센스 가닥의 3'-말단 뉴클레오티드의 3'-위치에 부착된다. 대안적인 실시형태에서, 리간드는 센스 가닥의 3' 말단 근처에, 그러나 하나 이상의 말단 뉴클레오티드 전에(즉 1, 2, 3, 또는 4 말단 뉴클레오티드 전에) 부착된다. 일부 실시형태에서, 리간드는 센스 가닥의 3'-말단 뉴클레오티드의 당의 2'-위치에 부착된다.
특정 실시형태에서, 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 30개의 원자 길이, 약 2 내지 약 28개의 원자 길이, 약 3 내지 약 26개의 원자 길이, 약 4 내지 약 24개의 원자 길이, 약 6 내지 약 20개의 원자 길이, 약 7 내지 약 20개의 원자 길이, 약 8 내지 약 20개의 원자 길이, 약 8 내지 약 18개의 원자 길이, 약 10 내지 약 18개의 원자 길이, 및 약 12 내지 약 18개의 원자 길이일수 있다. 일부 실시형태에서, 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 실시형태에서, 링커는 사슬 구조 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 제한되지는 않는다. 일부 실시형태에서, 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-아미노헥산 산, 치환된 C1-C10 알킬, 치환된 또는 비치환된 C2-C10 알케닐 또는 치환된 또는 비치환된 C2-C10 알키닐을 포함하지만, 이에 제한되지 않는다. 이러한 링커에 대한 바람직한 치환기는 히드록실, 아미노, 알콕시, 카르복시, 벤질, 페닐, 니트로, 티올, 티오알콕시, 할로겐, 알킬, 아릴, 알케닐 및 알키닐을 포함하지만, 이에 제한되지는 않는다.
특정 실시형태에서, 링커는 절단가능하다. 절단성 링커는 세포 외부에서 충분히 안정하지만, 표적 세포로 진입시 절단되어, 링커가 함께 유지되는 두 부분을 해제하는 링커이다. 일부 실시형태에서, 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 산화환원제로서, 예를 들어 산화 또는 환원성 효소 또는 환원에 의해 산화환원 절단성 링커를 분해할 수 있는, 세포에 존재하는 환원제 예컨대 머캅탄을 포함하는 산화환원제; 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 실시형태에서, 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 실시형태에서, 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 당 업계에 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 실시형태에서, 후보 링커는 혈액에서 최대 10%까지 절단된다. 다른 실시형태에서, 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 실시형태에서, 포스페이트-기반 절단성 링커는 포스페이트기를 분해하거나 가수분해하는 작용제에 의해 절단된다. 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-, -O-P(S)(Rk)-S-이다. 특정 실시형태는 -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-, -SP(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-, -O-P(S)(H)-S-를 포함한다. 다른 특정 실시형태는 -O-P(O)(OH)-O-이다. 이들 후보 링커는 상기 기술된 것과 유사한 방법을 사용하여 평가될 수 있다.
다른 실시형태에서, 링커는 산성 조건 하에서 절단되는 기인, 산 절단성 기를 포함할 수 있다. 일부 실시형태에서, 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 실시형태는 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 실시형태에서, 링커는 에스테르-기반 절단성 기를 포함할 수 있으며, 이는 세포에서 효소, 예컨대 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.
추가의 실시형태에서, 링커는 펩타이드-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 포함하지 않는다. 아미드 기는 임의의 알킬렌, 알케닐렌 또는 알키넬렌 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 생성하는 펩타이드 결합(즉, 아미드 결합)으로 제한되며, 전체 아미드 작용기를 포함하지 않는다. 펩타이드-기반 절단성 연결기는 일반 화학식 -NHCHRAC(O)NHCHRBC(O)-을 가지며, 여기서 RA 및 RB는 2개의 인접한 아미노산의 R 기이다. 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 당 업계에 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 실시형태에서, 본 발명의 RNAi 작제물의 센스 또는 안티센스 가닥에 공유적으로 부착된 리간드는 GalNAc 모이어티, 예를 들어 다가 GalNAc 모이어티를 포함한다. 일부 실시형태에서, 다가 GalNAc 모이어티는 3가 GalNAc 모이어티이며, 센스 가닥의 3' 말단에 부착된다. 다른 실시형태에서, 다가 GalNAc 모이어티는 3가 GalNAc 모이어티이며, 센스 가닥의 5' 말단에 부착된다. 또 다른 실시형태에서, 다가 GalNAc 모이어티는 4가 GalNAc 모이어티이며, 센스 가닥의 3' 말단에 부착된다. 또 다른 실시형태에서, 다가 GalNAc 모이어티는 4가 GalNAc 모이어티이며, 센스 가닥의 5' 말단에 부착된다.
일부 실시형태에서, 본 발명의 RNAi 작제물은 RNAi 작제물의 세포내 발현을 암호화하고 제어하는 벡터를 투여함으로써 관심 세포 또는 조직으로 전달될 수 있다. "벡터"(본원에서 "발현 벡터"라고도 함)는 세포의 내부로 관심 핵산을 전달하는데 사용될 수 있는 물질의 조성물이다. 선형 폴리뉴클레오티드, 이온성 또는 양친매성 화합물과 관련된 폴리뉴클레오티드, 플라스미드 및 바이러스를 포함하지만 이에 제한되지 않는 여러 벡터들이 당 업계에 공지되어 있다. 따라서, 용어 "벡터"는 자율 복제 플라스미드 또는 바이러스를 포함한다. 바이러스 벡터의 예는 아데노바이러스 벡터, 아데노-관련 바이러스 벡터, 레트로바이러스 벡터 등을 포함하지만, 이에 제한되지 않는다. 벡터는 살아있는 세포에서 복제될 수 있거나 합성적으로 제조될 수 있다.
일반적으로, 본 발명의 RNAi 작제물을 발현하기 위한 벡터는 RNAi 작제물을 암호화하는 서열에 작동가능하게 연결된 하나 이상의 프로모터를 포함할 것이다. 본원에 사용된 어구 "작동가능하게 연결된" 또는 "전사 제어하에"는 RNA 폴리머라제에 의한 전사의 개시 및 폴리뉴클레오티드 서열의 발현을 제어하기 위해 프로모터가 폴리뉴클레오티드 서열과 관련하여 정확한 위치 및 배향에 있음을 의미한다. "프로모터"는 유전자 서열의 특이적 전사를 개시하는데 필요한 세포의 합성기구 또는 도입된 합성기구에 의해 인식되는 서열을 지칭한다. 적합한 프로모터는 RNA pol I, pol II, HI 또는 U6 RNA pol III, 및 바이러스 프로모터(예를 들어, 인간 사이토메갈로 바이러스(CMV) 즉시 초기 유전자 프로모터, SV40 초기 프로모터 및 Rous 육종 바이러스 긴 말단 반복서열)를 포함하지만, 이에 제한되지 않는다. 일부 실시형태에서, HI 또는 U6RNA pol III 프로모터가 바람직하다. 프로모터는 조직-특이적 또는 유도성 프로모터일 수 있다. 간-특이적 프로모터, 예컨대 인간 알파!-항트립신 유전자, 알부민 유전자, 헤모펙신 유전자, 및 간 리파제 유전자로부터의 프로모터 서열이 특히 흥미롭다. 유도성 프로모터는 엑디손, 에스트로겐, 프로게스테론, 테트라사이클린 및 이소프로필-PD1-티오갈락토피라노시드(IPTG)에 의해 조절되는 프로모터를 포함한다.
RNAi 작제물이 siRNA를 포함하는 일부 실시형태에서, 2개의 개별 가닥 (센스 및 안티센스 가닥)은 단일 벡터 또는 2개의 개별 벡터로부터 발현될 수 있다. 예를 들어, 일 실시형태에서, 센스 가닥을 암호화하는 서열은 제1 벡터상의 프로모터에 작동가능하게 연결되고 안티센스 가닥을 암호화하는 서열은 제2 벡터상의 프로모터에 작동가능하게 연결된다. 상기 실시형태에서, 제1 및 제2 벡터는 예를 들어, 감염 또는 형질감염에 의해 표적 세포 내로 공동 도입되어, 일단 전사된 센스 및 안티센스 가닥이 세포내에서 하이브리드화되어, siRNA 분자를 형성할 것이다. 또 다른 실시형태에서, 센스 및 안티센스 가닥은 단일 벡터에 위치한 2개의 별개의 프로모터로부터 전사된다. 일부 상기 실시형태에서, 센스 가닥을 암호화하는 서열은 제1 프로모터에 작동가능하게 연결되고 안티센스 가닥을 암호화하는 서열은 제2 프로모터에 작동가능하게 연결되며, 여기서 제1 및 제2 프로모터는 단일 벡터에 위치된다. 일 실시형태에서, 벡터는 siRNA 분자를 암호화하는 서열에 작동가능하게 연결된 제1 프로모터, 및 동일한 서열에 반대 방향으로 작동가능하게 연결된 제2 프로모터를 포함하여, 제1 프로모터로부터의 서열의 전사는 siRNA 분자의 센스 가닥의 합성을 초래하고, 제2 프로모터로부터의 서열의 전사는 siRNA 분자의 안티센스 가닥의 합성을 초래한다.
RNAi 작제물이 shRNA를 포함하는 다른 실시형태에서, 단일의, 적어도 부분적으로 자기-상보성 RNA 분자를 암호화하는 서열은 프로모터에 작동가능하게 연결되어, 단일 전사물을 생성한다. 일부 실시형태에서, shRNA를 암호화하는 서열은 링커 폴리뉴클레오티드 서열에 의해 연결된 역반복을 포함하여 전사후 shRNA의 줄기 및 루프 구조를 생성한다.
일부 실시형태에서, 본 발명의 RNAi 작제물을 암호화하는 벡터는 바이러스 벡터이다. 본원에 기재된 RNAi 작제물을 발현시키기에 적합한 다양한 바이러스 벡터 시스템은 아데노바이러스 벡터, 레트로바이러스 벡터(예를 들어, 렌티바이러스 벡터, 말로니 뮤린 백혈병 바이러스(maloney murine leukemia virus)), 아데노-관련 바이러스 벡터; 단순포진 바이러스 벡터; SV 40 벡터; 폴리오마 바이러스 벡터; 유두종 바이러스 벡터; 피코나비랄 벡터; 및 폭스 바이러스 벡터 (예를 들어, 백시니아 바이러스)를 포함하지만, 이에 제한되지 않는다. 특정 실시형태에서, 바이러스 벡터는 레트로바이러스 벡터(예를 들어, 렌티바이러스 벡터)이다.
본 발명에 사용하기에 적합한 다양한 벡터, siRNA 또는 shRNA 분자를 암호화하는 핵산 서열을 벡터에 삽입하는 방법, 및 벡터를 관심 세포에 전달하는 방법은 당업자의 기술 범위내에 있다. 예를 들어, Dornburg , Gene Therap., Vol. 2: 301-310, 1995; Eglitis, Biotechniques, Vol. 6: 608-614, 1988; Miller, HumGene Therap., Vol. 1: 5-14, 1990; Anderson, Nature, Vol. 392: 25-30, 1998; Rubinson D A et al., Nat. Genet., Vol. 33: 401-406, 2003; Brummelkamp et al., Science, Vol. 296: 550-553, 2002;Brummelkamp et al., Cancer Cell, Vol. 2: 243-247, 2002; Lee et al., Nat Biotechnol, Vol. 20:500-505, 2002; Miyagishi et al., Nat Biotechnol, Vol. 20: 497-500, 2002; Paddison et al., GenesDev, Vol. 16: 948-958, 2002; Paul et al., Nat Biotechnol, Vol. 20: 505-508, 2002; Sui et al., ProcNatl Acad Sci USA, Vol. 99: 5515-5520, 2002; 및 Yu et al., Proc Natl Acad Sci USA, Vol. 99:6047-6052, 2002를 참고하며, 이들 모두는 그 전문이 본원에 참조로 포함된다.
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 대상체에서 PNPLA3의 발현을 감소시키는 데 유용하다. 임상 적용이 고려되는 경우, 약제학적 조성물 및 제형은 의도된 적용에 적합한 형태로 제조될 것이다. 일반적으로, 이것은 발열원뿐만 아니라 인간 또는 동물에게 해로울 수 있는 다른 불순물이 본질적으로 없는 조성물의 제조를 수반할 것이다.
구절 "약제학적으로 허용가능한" 또는 "약리학적으로 허용가능한"은 동물 또는 인간에 투여시 이상 반응, 알레르기 반응, 또는 다른 부작용을 생성하지 않는 분자 개체 및 조성물을 의미한다. 본 명세서에 사용된 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 당해 분야에 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 벡터 또는 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 실시형태에서, 약제학적 조성물은 의도된 전달 경로에 기초하여 제형화된다. 예를 들어, 특정 실시형태에서, 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 실시형태에서, 약제학적 조성물은 정맥 내 전달용으로 제형화된다. 상기 실시형태에서, 약제학적 조성물은 지질-계 전달 비히클을 포함할 수 있다. 또 다른 실시형태에서, 약제학적 조성물은 피하 전달용으로 제형화된다. 상기 실시형태에서, 약제학적 조성물은 표적화 리간드(예를 들어, 본원에 기재된 GalNAc 함유 리간드)를 포함할 수 있다.
일부 실시형태에서, 약제학적 조성물은 본원에 기재된 유효량의 RNAi 작제물을 포함한다. "유효량"은 유익하거나 바람직한 임상 결과를 생성하기에 충분한 양이다. 일부 실시형태에서, 유효량은 대상체의 간세포에서 PNPLA3 발현을 감소시키기에 충분한 양이다. 일부 실시형태에서, 유효량은 PNPLA3 발현을 부분적으로만, 예를 들어 인간 이형접합체에서 야생형 PNPLA3 대립유전자의 발현에 필적하는 수준으로만 감소시키기에 충분한 양일 수 있다. 기능 손실 PNPLA3 변이 대립유전자의 인간 이형접합체 담체는 비-HDL 콜레스테롤의 혈청 수준이 더 낮고, 비-담체에 비해 관상 동맥 질환 및 심근 경색의 위험이 더 낮은 것으로 보고되었다(Nioi et al., New England Journal of Medicine, Vol. 374(22):2131-2141, 2016). 따라서, 이론에 구속되지 않고, PNPLA3 발현의 부분 감소는 혈청 비-HDL 콜레스테롤의 유익한 감소 및 관상 동맥 질환 및 심근 경색의 위험 감소를 달성하기에 충분할 것으로 여겨진다.
본 발명의 RNAi 작제물의 유효량은 약 0.01 mg/kg 체중 내지 약 100 mg/kg 체중, 약 0.05 mg/kg 체중 내지 약 75 mg/kg 체중, 약 0.1 mg/kg 체중 내지 약 50 mg/kg 체중, 약 1 mg/kg 내지 약 30 mg/kg 체중, 약 2.5 mg/kg 체중 내지 약 20 mg/kg 체중, 또는 약 5 mg/kg 체중 내지 약 15 mg/kg 체중일 수 있다. 특정 실시형태에서, 본 발명의 RNAi 작제물의 단일 유효량은 약 0.1 mg/kg, 약 0.5 mg/kg, 약 1 mg/kg, 약 2 mg/kg, 약 3 mg/kg, 약 4 mg/kg, 약 5 mg/kg, 약 6 mg/kg, 약 7 mg/kg, 약 8 mg/kg, 약 9 mg/kg, 또는 약 10 mg/kg일 수 있다. 유효량의 RNAi 작제물을 포함하는 약제학적 조성물은 매주, 격주, 매월, 분기 또는 2년마다 투여될 수 있다. 유효한 양 및 투여 빈도로 간주되는 것의 정확한 결정은 환자의 키, 연령 및 일반적인 상태, 치료될 장애의 유형(예를 들어, 심근 경색, 심부전, 관상 동맥 질환, 고 콜레스테롤 혈증), 사용된 특정 RNAi 작제물 및 투여 경로를 비롯한 여러 요인에 기초할 수 있다. 본 발명의 임의의 특정 RNAi 작제물에 대한 유효량 및 생체내 반감기의 추정치는 통상적인 방법 및/또는 적절한 동물 모델에서의 시험을 사용하여 확인할 수 있다.
본 발명의 약제학적 조성물의 투여는 표적 조직이 상기 경로를 통해 이용 가능한 한 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 실시형태에서, 약제학적 조성물은 비경구 투여된다. 예를 들어, 특정 실시형태에서, 약제학적 조성물은 정맥 내 투여된다. 다른 실시형태에서, 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 비히클 또는 이러한 작제물을 암호화하는 벡터로 사용될 수 있다. 본 발명의 핵산을 전달하는데 적합한 시판되는 지방 에멀젼은 Intralipid®, Liposyn®, Liposyn®II, Liposyn®III, 뉴트리리피드(Nutrilipid), 및 기타 유사한 지질 에멀젼을 포함한다. 생체내 전달 비히클로 사용하기에 바람직한 콜로이드 시스템은 리포좀(즉, 인공 막 소포)이다. 본 발명의 RNAi 작제물은 리포좀 내에 캡슐화될 수 있거나, 특히 양이온성 리포좀에 대한 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 당 업계에 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 W003/093449에 개시되어 있다.
일부 실시형태에서, 본 발명의 RNAi 작제물은 예를 들어, SPLP, pSPLP, SNALP, 또는 다른 핵산-지질 입자를 형성하기 위해 지질 제형으로 완전히 캡슐화된다. 본 명세서에 사용된 바와 같이, 용어 "SNALP"는 SPLP를 포함하는 안정한 핵산-지질 입자를 지칭한다. 본 명세서에 사용된 바와 같이, 용어 "SPLP"는 지질 소포 내에 캡슐화된 플라스미드 DNA를 포함하는 핵산-지질 입자를 지칭한다. SNALP 및 SPLP는 전형적으로 양이온성 지질, 비 양이온성 지질 및 입자의 응집을 방지하는 지질(예를 들어, PEG-지질 접합체)을 함유한다. SNALP 및 SPLP는 정맥내 주사후 연장된 순환 수명을 나타내고 원위 부위(예를 들어, 투여 부위와 물리적으로 분리된 부위)에서 축적함에 따라 전신 용도에 특별히 유용하다. SPLP는 PCT 공개 번호 WO00/03683에 개시된 캡슐화된 축합제-핵산 복합체를 포함하는 "pSPLP"를 포함한다. 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 PCT 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 주사가 용이하게 가능할 만큼 멸균 및 유동적이다. 제제는 제조 및 저장 조건 하에서 안정하여야 하고, 박테리아 및 진균과 같은 미생물의 오염 작용에 대해 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 유동도(fluidity)는 예를 들어 레시틴과 같은 코팅의 사용에 의해, 분산액의 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. 주사가능한 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)으로부터 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 제2 철)로부터 또는 유기 염기(예를 들어, 이소프로필아민, 트리메틸아민, 히스티딘, 프로카인 등)로부터 유래될 수 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 실시형태에서, 본 발명의 약제학적 조성물은 멸균 식염수 용액 및 본원에 기재된 RNAi 작제물을 포함하거나 이로 구성된다. 다른 실시형태에서, 본 발명의 약제학적 조성물은 본원에 기재된 RNAi 작제물 및 멸균 수(예를 들어, 주사용수, WFI)를 포함하거나 이로 구성된다. 또 다른 실시형태에서, 본 발명의 약제학적 조성물은 본원에 기재된 RNAi 작제물 및 포스페이트-완충 식염수(PBS)를 포함하거나 이로 구성된다.
일부 실시형태에서, 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 장애를 치료 또는 예방하기 위한 본 발명의 약제학적 조성물을 포함하는 투여 장치를 포함한다.
PNPLA3 발현을 억제하는 방법
본 발명은 또한 세포에서 PNPLA3 유전자의 발현을 억제하는 방법을 제공한다. 상기 방법은 세포에서 PNPLA3의 발현을 억제하는데 효과적인 양으로 세포를 RNAi 작용제, 예를 들어 이중 가닥 RNAi 작용제와 접촉시켜 세포에서 PNPLA3의 발현을 억제하는 단계를 포함한다. 세포를 RNAi 작용제, 예를 들어 이중 가닥 RNAi 작용제와 접촉시키는 것은 시험관내 또는 생체내에서 수행될 수 있다. 생체내에서 RNAi 작용제와 세포를 접촉시키는 것은 대상체, 예를 들어 인간 대상체 내의 세포 또는 세포 그룹을 RNAi 작용제와 접촉시키는 것을 포함한다. 세포를 접촉시키는 시험관내 및 생체내 방법의 조합이 또한 가능하다.
본 발명은 PNPLA3 발현 또는 활성과 관련된 병태, 질환 또는 장애를 치료 또는 예방하는 방법뿐만 아니라 이를 필요로 하는 대상체에서 PNPLA3의 발현을 감소 또는 억제하는 방법을 제공한다. "PNPLA3 발현과 관련된 병태, 질환 또는 장애"는 PNPLA3 발현 수준이 변경되거나 PNPLA3의 증가된 발현 수준이 병태, 질환 또는 장애의 발병 위험 증가와 관련되는 경우의 병태, 질환 또는 장애를 지칭한다.
세포에 접촉하는 것은 전술한 바와 같이 직접적이거나 간접적일 수 있다. 또한, 세포 접촉은 본원에 기술되거나 당 업계에 공지된 임의의 리간드를 포함하는 표적화 리간드를 통해 달성될 수 있다. 바람직한 실시형태에서, 표적화 리간드는 탄수화물 모이어티, 예를 들어, GalNAc3 리간드, 또는 RNAi 작용제를 관심 부위로 유도하는 임의의 다른 리간드이다.
일 실시형태에서, 세포를 RNAi와 접촉시키는 것은 세포 내로의 흡수 또는 흡인을 촉진하거나 수행함으로써 "RNAi를 세포 내로 도입"하거나 "전달"하는 것을 포함한다. RNAi의 흡수 또는 흡인은 원치 않는 확산 또는 활성 세포 과정 또는 보조제 또는 장치를 통해 발생할 수 있다. RNAi를 세포 내로 도입하는 것은 시험관내 및/또는 생체내일 수 있다. 예를 들어, 생체내 도입을 위해, RNAi는 조직 부위에 주사되거나 전신 투여될 수 있다. 세포로의 시험관내 도입은 전기천공 및 리포펙션과 같은 당 업계에 공지된 방법을 포함한다. 추가의 접근법이 이하에 설명되고/되거나 당 업계에 공지되어 있다.
본 명세서에 사용된 바와 같이, 용어 "억제하는"은 "감소하는", "사일런싱", "하향조절하는", "억제하는" 및 다른 유사한 용어들과 상호교환적으로 사용되며, 임의의 수준의 억제를 포함한다.
어구 "PNPLA3의 발현 억제"는 임의의 PNPLA3 유전자(예컨대, 예를 들어, 마우스 PNPLA3 유전자, 래트 PNPLA3 유전자, 원숭이 PNPLA3 유전자, 또는 인간 PNPLA3 유전자) 뿐만 아니라 PNPLA3 유전자의 변이체 또는 돌연변이체의 발현 억제를 지칭하는 것으로 의도된다. 따라서, PNPLA3 유전자는 유전자 조작된 세포, 세포 그룹, 또는 유기체의 맥락에서 야생형 PNPLA3 유전자, 돌연변이 PNPLA3 유전자(예컨대 아밀로이드 침착을 야기하는 돌연변이 PNPLA3 유전자), 또는 트랜스제닉 PNPLA3 유전자일 수 있다.
"PNPLA3 유전자의 발현 억제"는 PNPLA3 유전자의 임의의 억제 수준, 예를 들어, PNPLA3 유전자의 발현의 적어도 부분적 억제를 포함한다. PNPLA3 유전자의 발현은 PNPLA3 유전자 발현과 관련된 임의의 변수, 예를 들어, PNPLA3 mRNA 수준, PNPLA3 단백질 수준, 또는 아밀로이드 침착물의 수 또는 정도의 수준, 또는 수준 변화에 기초하여 평가될 수 있다. 이 수준은 예를 들어 대상체로부터 유래된 샘플을 포함하여 개별 세포 또는 세포 그룹에서 평가될 수 있다.
억제는 대조군 수준과 비교하여 PNPLA3 발현과 관련된 하나 이상의 변수의 절대적 또는 상대적 수준의 감소에 의해 평가될 수 있다. 대조군 수준은 당 업계에서 이용되는 임의의 유형의 대조군 수준, 예를 들어, 투여 전 기준선 수준, 또는 대조군(예컨대, 예를 들어, 완충액 단독 대조군 또는 불활성 제제 대조군)으로 처리되거나 처리되지 않은 유사한 대상체, 세포 또는 샘플로부터 측정된 수준일 수 있다. 본 발명의 방법의 일부 실시형태에서, PNPLA3 유전자의 발현은 적어도 약 5%, 적어도 약 10%, 적어도 약 15%, 적어도 약 20%, 적어도 약 25%, 적어도 약 30%, 적어도 약 35%, 적어도 약 40%, 적어도 약 45%, 적어도 약 50%, 적어도 약 55%, 적어도 약 60%, 적어도 약 65%, 적어도 약 70%, 적어도 약 75%, 적어도 약 80%, 적어도 약 85%, 적어도 약 90%, 적어도 약 91%, 적어도 약 92%, 적어도 약 93%, 적어도 약 94%. 적어도 약 95%, 적어도 약 96%, 적어도 약 97%, 적어도 약 98%, 또는 적어도 약 99% 억제된다.
PNPLA3 유전자의 발현의 억제는 PNPLA3 유전자가 전사되고, (예를 들어, 세포 또는 세포들을 본 발명의 RNAi 작용제와 접촉시킴으로써, 또는 세포들이 존재하거나 존재했던 대상체에 본 발명의 RNAi 작용제를 투여함으로써) 치료되었거나 치료된 제1 세포 또는 세포 그룹(이러한 세포는 예를 들어 대상체로부터 유래된 샘플에 존재할 수 있음)에 의해 발현되는 mRNA의 양의 감소에 의해 나타날 수 있으며, 따라서 PNPLA3 유전자의 발현은 제1 세포 또는 세포 그룹과 실질적으로 동일하지만 그렇게 처리되지 않았거나 그렇지 않은 제2 세포 또는 세포 그룹(대조군 세포(들))과 비교하여 억제된다. 바람직한 실시형태에서, 억제는 하기 식을 사용하여, 처리된 세포에서의 mRNA 수준을 대조군 세포에서의 mRNA 수준의 백분율로서 표현함으로써 평가된다:
대안적으로, PNPLA3 유전자의 발현 억제는 PNPLA3 유전자 발현, 예를 들어, PNPLA3 단백질 발현 또는 고슴도치(Hedgehog) 경로 단백질 활성과 기능적으로 연결된 파라미터의 감소의 관점에서 평가될 수 있다. PNPLA3 유전자 사일런싱은 PNPLA3을 발현하는 임의의 세포에서 구성적으로 또는 게놈 공학에 의해, 그리고 당 업계에 공지된 임의의 분석에 의해 결정될 수 있다.
PNPLA3 단백질의 발현 억제는 세포 또는 세포 그룹에 의해 발현되는 PNPLA3 단백질의 수준(예를 들어, 대상체로부터 유래된 샘플에서 발현된 단백질의 수준)의 감소에 의해 나타날 수 있다. 전술한 바와 같이, mRNA 억제의 평가를 위해, 처리된 세포 또는 세포 그룹에서 단백질 발현 수준의 억제는 대조군 세포 또는 세포 그룹에서 단백질 수준의 백분율로 유사하게 표현될 수 있다.
PNPLA3 유전자의 발현 억제를 평가하기 위해 사용될 수 있는 대조군 세포 또는 세포 그룹은 본 발명의 RNAi 작용제와 아직 접촉되지 않은 세포 또는 세포 그룹을 포함한다. 예를 들어, 대조군 세포 또는 세포 그룹은 RNAi 작용제로 대상체를 치료하기 전에 개별 대상체(예를 들어, 인간 또는 동물 대상체)로부터 유래될 수 있다.
세포 또는 세포 그룹에 의해 발현되는 PNPLA3 mRNA의 수준, 또는 순환 PNPLA3 mRNA의 수준은 mRNA 발현을 평가하기 위해 당 업계에 공지된 임의의 방법을 사용하여 결정될 수 있다. 일 실시형태에서, 샘플에서 PNPLA3의 발현 수준은 전사된 폴리뉴클레오티드 또는 이의 일부, 예를 들어 PNPLA3 유전자의 mRNA를 검출함으로써 결정된다. RNA는 예를 들어, 산 페놀/구아니딘 이소티오시아네이트 추출(RNAzol B; Biogenesis), RNeasy RNA 준비 키트(Qiagen) 또는 PAXgene(PreAnalytix, Switzerland)을 포함하는 RNA 추출 기술을 사용하여 세포로부터 추출될 수 있다. 리보핵산 하이브리드화를 이용하는 전형적인 분석 포맷은 핵 런-온 분석, RT-PCR, RNase 보호 분석(Melton et al., Nuc. Acids Res. 12:7035), 노던 블롯팅, 인시추 하이브리드화 및 마이크로어레이 분석을 포함한다. 순환 PNPLA3 mRNA는 PCT/US2012/043584에 기술된 방법을 사용하여 검출될 수 있으며, 이의 전체 내용은 본원에 참조로 포함된다.
일 실시형태에서, PNPLA3의 발현 수준은 핵산 프로브를 사용하여 결정된다. 본 명세서에 사용된 바와 같이, 용어 "프로브"는 특정 PNPLA3에 선택적으로 결합할 수 있는 임의의 분자를 지칭한다. 프로브는 당업자에 의해 합성되거나 적절한 생물학적 제제로부터 유래될 수 있다. 프로브는 표지되도록 특별히 설계될 수 있다. 프로브로서 이용될 수 있는 분자의 예는 RNA, DNA, 단백질, 항체 및 유기 분자를 포함하지만 이에 제한되지는 않는다.
단리된 mRNA는 서던 또는 노던 분석, 중합효소 연쇄 반응 (PCR) 분석 및 프로브 분석을 포함하지만, 이에 제한되지 않는 하이브리드화 또는 증폭 분석에 사용될 수 있다. mRNA 수준의 결정을 위한 하나의 방법은 단리된 mRNA를 PNPLA3 mRNA에 하이브리드화할 수 있는 핵산 분자(프로브)와 접촉시키는 단계를 포함한다. 일 실시형태에서, mRNA는 고체 표면에 고정되고, 예를 들어 단리된 mRNA를 아가로스 겔상에서 러닝시키고 mRNA를 겔에서 니트로셀룰로스와 같은 막으로 전달함으로써 프로브와 접촉된다. 대안적인 실시형태에서, 프로브(들)는 고체 표면 상에 고정되고 mRNA는 예를 들어 Affymetrix 유전자 칩 어레이에서 프로브(들)와 접촉된다. 당업자는 PNPLA3 mRNA의 수준을 결정하는데 사용하기 위해 공지된 mRNA 검출 방법을 용이하게 적용할 수 있다.
샘플내 PNPLA3의 발현 수준을 결정하기 위한 대안적인 방법은 예를 들어, RT-PCR(Mullis, 1987, 미국 특허 제4,683,202호에 제시된 실험적 실시형태), 리가제 연쇄 반응(Barany (1991) Proc. Natl. Acad. Sci. USA 88: 189-193), 자가 지속 서열 복제(Guatelli et al. (1990) Proc. Natl. Acad. Sci. USA 87: 1874-1878), 전사 증폭 시스템(Kwoh et al. (1989) Proc. Natl. Acad. Sci. USA 86: 1173-1177), Q-베타 레플리카제(Lizardi et al. (1988) Bio/Technology 6: 1197), 롤링 서클 복제(Lizardi et al., 미국 특허 제5,854,033호) 또는 임의의 다른 핵산 증폭 방법에 이어, 당업자들에게 잘 알려진 기술을 사용한 증폭된 분자의 검출에 의해 예를 들어 샘플내 mRNA의 핵산 증폭 및/또는 역전사효소(cDNA를 제조하기 위한)의 과정을 포함한다. 이러한 검출 방식은 그러한 분자가 매우 적은 수로 존재하는 경우 핵산 분자의 검출에 특히 유용하다. 본 발명의 특정 양태에서, PNPLA3의 발현 수준은 정량적 형광성 RT-PCR{즉, TaqMan™ System)에 의해 결정된다. PNPLA3 mRNA의 발현 수준은 막 블롯(예컨대 노던, 서던, 도트 등과 같은 하이브리드화 분석에 사용됨), 또는 마이크로웰, 샘플 튜브, 겔, 비드 또는 섬유 (또는 결합된 핵산을 포함하는 임의의 고체 지지체)를 사용하여 모니터링될 수 있다. 미국 특허 제5,770,722호, 제5,874,219호, 제5,744,305호, 제5,677,195호 및 제5,445,934호를 참고하며, 이들은 본원에 참고로 포함된다. PNPLA3 발현 수준의 결정은 또한 용액 중의 핵산 프로브를 사용하는 것을 포함할 수 있다.
바람직한 실시형태에서, mRNA 발현의 수준은 분지형 DNA (bDNA) 분석 또는 실시간 PCR (qPCR)을 사용하여 평가된다. 이들 방법의 사용은 본원에 제시된 실시예에서 설명되고 예시된다.
PNPLA3 단백질 발현의 수준은 단백질 수준의 측정을 위해 당 업계에 공지된 임의의 방법을 사용하여 결정될 수 있다. 이러한 방법은 예를 들어 전기영동, 모세관 전기영동, 고성능 액체 크로마토그래피(HPLC), 박층 크로마토그래피(TLC), 과확산 크로마토그래피, 유체 또는 겔 프리시피틴(precipitin) 반응, 흡수 분광법, 비색 분석, 분광 광도 분석, 유세포 분석, 면역확산(단일 또는 이중), 면역전기영동, 웨스턴 블로팅, 방사선면역분석(RIA), 효소-결합 면역흡착 분석(ELISA), 면역형광 분석, 전기화학발광 분석 등을 포함한다.
일부 실시형태에서, 본 발명의 방법의 효능은 PNPLA3 질환의 증상 감소, 예를 들어 사지, 얼굴, 후두, 상부 호흡기, 복부, 몸통 및 생식기의 부종(edema swelling), 전구증상; 후두 부종; 비소 양성 발진; 구역질; 구토; 또는 복통의 감소를 검출 또는 모니터링함으로써 모니터링될 수 있다. 이들 증상은 관련 기술 분야에 공지된 임의의 방법을 사용하여 시험관내 또는 생체내에서 평가될 수 있다.
본 발명의 방법의 일부 실시형태에서, RNAi 작용제가 대상체에 투여되어, RNAi 작용제가 대상체내 특정 부위로 전달되도록 한다. PNPLA3의 발현 억제는 대상체 내의 특정 부위로부터의 유체 또는 조직으로부터 유래된 샘플에서 PNPLA3 mRNA 또는 PNPLA3 단백질의 수준 또는 수준 변화 측정을 사용하여 평가될 수 있다. 바람직한 실시형태에서, 부위는 간, 맥락막총, 망막 및 췌장으로 구성된 군에서 선택된다. 상기 부위는 또한 상기 언급된 부위 중 어느 하나로부터의 세포의 서브섹션 또는 서브 그룹일 수 있다. 부위는 또한 특정 유형의 수용체를 발현하는 세포를 포함할 수 있다.
PNPLA3-관련 질환의 치료 또는 예방 방법
본 발명은 PNPLA3-관련 질환, 장애 및/또는 병태를 갖는 대상체, 또는 PNPLA3-관련 질환, 장애 및/또는 병태가 발생하기 쉬운 대상체에게, RNAi 작용제를 포함하는 조성물, 또는 RNAi 작용제를 포함하는 약제학적 조성물, 또는 본 발명의 RNAi를 포함하는 벡터를 투여하는 단계를 포함하는 치료 및 예방 방법을 제공한다. PNPLA3-관련 질환의 비-제한적 예는 예를 들어, 지방간(지방증), 비알코올성 지방간염(NASH), 간경변, 간에서의 지방 축적, 간 염증, 간세포 괴사, 간 섬유증, 비만, 또는 비알코올성 지방간 질환(NAFLD)을 포함한다. 일 실시형태에서, PNPLA3-관련 질환은 NAFLD이다. 또 다른 실시형태에서, PNPLA3-관련 질환은 NASH이다. 또 다른 실시형태에서, PNPLA3-관련 질환은 지방간(지방증)이다. 또 다른 실시형태에서, PNPLA3-관련 질환은 인슐린 저항성이다. 또 다른 실시형태에서, PNPLA3-관련 질환은 인슐린 저항성이 아니다.
특정 실시형태에서, 본 발명은 본원에 기재된 임의의 RNAi 작제물을 PNPLA3 발현의 감소를 필요로 하는 환자에게 투여하는 단계를 포함하는, 환자에서의 PNPLA3의 발현을 감소시키는 방법을 제공한다. 용어 "환자"는, 본 명세서에 사용된 바와 같이, 인간을 포함하는 포유동물을 지칭하고, 용어 "대상체"와 상호교환적으로 사용될 수 있다. 바람직하게는, 환자의 간세포에서 PNPLA3의 발현 수준은 RNAi 작제물을 수용하지 않는 환자에서의 PNPLA3 발현 수준과 비교하여 RNAi 작제물의 투여 후 감소된다.
본 발명의 방법은 PNPLA3-관련 질환을 갖는 대상체, 예를 들어 PNPLA3 유전자 발현 및/또는 PNPLA3 단백질 생산의 감소로부터 이익을 얻을 수 있는 대상체를 치료하는데 유용하다. 일 양태에서, 본 발명은 비알코올성 지방간 질환(NAFLD)을 갖는 대상체에서 파타틴-유사 포스포리파제 도메인-함유 3(PNPLA3) 유전자 발현의 수준을 감소시키는 방법을 제공한다. 또 다른 양태에서, 본 발명은 NAFLD를 갖는 대상체에서 PNPLA3 단백질의 수준을 감소시키는 방법을 제공한다. 본 발명은 또한 NAFLD를 갖는 대상체에서 고슴도치 경로의 활성 수준을 감소시키는 방법을 제공한다.
또 다른 양태에서, 본 발명은 NAFLD를 갖는 대상체를 치료하는 방법을 제공한다. 일 양태에서, 본 발명은 PNPLA3-관련 질환, 예를 들어, 지방간(지방증), 비알코올성 지방간염(NASH), 간경변, 간에서의 지방 축적, 간 염증, 간세포 괴사, 간 섬유증, 비만, 또는 비알코올성 지방간 질환(NAFLD)을 갖는 대상체를 치료하는 방법을 제공한다. 본 발명의 치료 방법(및 용도)은 PNPLA3 유전자를 표적화하는 본 발명의 치료적으로 유효한 양의 RNAi 작용제 또는 PNPLA3 유전자를 표적화하는 본 발명의 RNAi 작용제를 포함하는 약제학적 조성물 또는 PNPLA3 유전자를 표적화하는 RNAi 작용제를 포함하는 본 발명의 벡터를 대상체, 예를 들어, 인간에게 투여하는 단계를 포함한다.
일 양태에서, 본 발명은 NAFLD를 갖는 대상체에서 적어도 하나의 증상 예를 들어 높은 고슴도치 신호전달 경로의 존재, 피로, 허약, 체중 감소, 식욕 부진, 구역질, 복통, 거미-유사 혈관, 피부 및 눈의 황변(황달), 가려움증, 체액 축적 및 다리 부종(부종), 복부 팽만(복수) 및 정신적 혼란을 예방하는 방법을 제공한다. 상기 방법은 치료적 유효량의 RNAi 작용제, 예를 들어 본 발명의 dsRNA, 약제학적 조성물, 또는 벡터를 대상체에 투여하여, PNPLA3 유전자 발현의 감소로부터 이익을 얻을 수 있는 장애를 갖는 대상체의 적어도 하나의 증상을 예방하는 단계를 포함한다.
또 다른 양태에서, 본 발명은 대상체, 예를 들어, PNPLA3 유전자 발현의 감소 및/또는 억제로부터 이익을 얻을 수 있는 대상체를 치료하기 위한 치료적 유효량의 본 발명의 RNAi 작용제의 용도를 제공한다. 추가의 양태에서, 본 발명은 대상체, 예를 들어, PNPLA3 유전자 발현 및/또는 PNPLA3 단백질 생성의 감소 및/또는 억제로부터 이익을 얻는 대상체, 예컨대 PNPLA3 유전자 발현 감소로부터 이익을 얻는 장애, 예를 들어, PNPLA3-관련 질환을 갖는 대상체를 치료하기 위한 약제의 제조에서 PNPLA3 유전자를 표적화하는 본 발명의 RNAi 작용제, 예를 들어, dsRNA 또는 PNPLA3 유전자를 표적화하는 RNAi 작용제를 포함하는 약제학적 조성물의 용도를 제공한다.
또 다른 양태에서, 본 발명은 PNPLA3 유전자 발현 및/또는 PNPLA3 단백질 생산의 감소 및/또는 억제로부터 이익을 얻는 장애를 앓고 있는 대상체의 적어도 하나의 증상을 예방하기 위한 본 발명의 RNAi, 예를 들어, dsRNA의 용도를 제공한다.
추가의 양태에서, 본 발명은 PNPLA3 유전자 발현 및/또는 PNPLA3 단백질 생산의 감소 및/또는 억제로부터 이익을 얻는 장애, 예컨대 PNPLA3-관련 질환을 앓고 있는 대상체의 적어도 하나의 증상을 예방하기 위한 약제의 제조에 있어서 본 발명의 RNAi 작용제의 용도를 제공한다.
일 실시형태에서, PNPLA3을 표적화하는 RNAi 작용제는 PNPLA3-관련 질환, 예를 들어, 비알코올성 지방간 질환 (NAFLD)을 갖는 대상체에 투여되어, dsRNA 작용제가 대상체에게 투여될 경우 예를 들어, 대상체의 세포, 조직, 혈액 또는 다른 조직 또는 체액에서 PNPLA3 유전자의 발현이 적어도 약 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 62%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 적어도 약 99% 이상 감소된다.
본 발명의 방법 및 용도는 본원에 기술된 조성물을 투여하는 단계를 포함하여, 표적 PNPLA3 유전자의 발현이 예컨대 약 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 18, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 또는 약 80시간 동안 감소된다. 일 실시형태에서, 표적 PNPLA3 유전자의 발현은 연장된 기간동안, 예를 들어, 적어도 약 2, 3, 4, 5, 6, 7일 이상, 예를 들어, 약 1주일, 2주일, 3주일, 또는 약 4주일 이상 동안 감소된다.
본 발명의 방법 및 용도에 따른 dsRNA의 투여는 PNPLA3-관련 질환, 예를 들어, 비알코올성 지방간 질환(NAFLD)을 갖는 환자의 상기 질환 또는 장애의 중증도, 징후, 증상 및/또는 마커를 감소시킬 수 있다. 이와 관련하여 "감소"는 이러한 수준의 통계적으로 유의미한 감소를 의미한다. 감소는 예를 들어, 적어도 약 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 또는 약 100%일 수 있다. 예를 들어 질병 진행, 질병 완화, 증상 중증도, 통증 감소, 삶의 질, 치료 효과를 유지하기 위해 필요한 약물의 복용량, 질병 마커의 수준 또는 치료 또는 예방 대상의 특정 질환에 적합한 임의의 다른 측정가능한 파라미터를 측정함으로써 치료의 효능 또는 질환 예방을 평가할 수 있다. 이러한 파라미터 중 임의의 하나 또는 임의의 파라미터의 조합을 측정함으로써 치료 또는 예방의 효능을 모니터링하는 것은 당업자의 능력 내에 있다. 예를 들어, NAFLD의 치료 효능은, 예를 들어 NAFLD 증상, 간 지방 수준, 또는 하류 유전자의 발현의 주기적 모니터링에 의해 평가될 수 있다. 초기 판독 값과 이후 판독 값의 비교는 의사에게 치료가 효과적인지 지표를 제공한다. 이러한 파라미터 중 임의의 하나 또는 임의의 파라미터의 조합을 측정함으로써 치료 또는 예방의 효능을 모니터링하는 것은 당업자의 능력 내에 있다. PNPLA3을 표적화하는 RNAi 또는 이의 약제학적 조성물의 투여와 관련하여, PNPLA3-관련 질환에 대한 "유효한"은 임상적으로 적절한 방식으로 투여하면 적어도 통계적으로 유의한 환자 분율에 유익한 효과, 예컨대 증상 개선, 치료, 질환 감소, 수명 연장, 삶의 질 개선, 또는 일반적으로 NAFLD 및/또는 PNPLA3-관련 질환 및 관련 원인의 치료에 친숙한 의사에 의해 긍정적인 것으로 인식되는 다른 효과를 가져온다는 것을 나타낸다.
치료 또는 예방 효과는 질환 상태의 하나 이상의 파라미터에서 통계적으로 유의미한 개선이 있거나, 그렇지 않으면 예상되는 증상을 악화시키거나 발전시키지 못하는 경우에 명백하다. 예로서, 질환의 측정가능한 파라미터에서 적어도 10%, 바람직하게는 적어도 20%, 30%, 40%, 50% 이상의 유리한 변화는 효과적인 치료를 나타낼 수 있다. 주어진 RNAi 약물 또는 그 약물의 제형에 대한 효능은 또한 당 업계에 공지된 주어진 질환에 대한 실험 동물 모델을 사용하여 판단될 수 있다. 실험 동물 모델을 사용하는 경우, 마커 또는 증상의 통계적으로 유의한 감소가 관찰될 때 치료 효능이 입증된다.
대상체는 치료량의 RNAi, 예컨대 약 0.01 mg/kg, 0.02 mg/kg, 0.03 mg/kg, 0.04 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.15 mg/kg, 0.2 mg/kg, 0.25 mg/kg, 0.3 mg/kg, 0.35 mg/kg, 0.4 mg/kg, 0.45 mg/kg, 0.5 mg/kg, 0.55 mg/kg, 0.6 mg/kg, 0.65 mg/kg, 0.7 mg/kg, 0.75 mg/kg, 0.8 mg/kg, 0.85 mg/kg, 0.9 mg/kg, 0.95 mg/kg, 1.0 mg/kg, 1.1 mg/kg, 1.2 mg/kg, 1.3 mg/kg, 1.4 mg/kg, 1.5 mg/kg, 1.6 mg/kg, 1.7 mg/kg, 1.8 mg/kg, 1.9 mg/kg, 2.0 mg/kg, 2.1 mg/kg, 2.2 mg/kg, 2.3 mg/kg, 2.4 mg/kg, 2.5 mg/kg dsRNA, 2.6 mg/kg dsRNA, 2.7 mg/kg dsRNA, 2.8 mg/kg dsRNA, 2.9 mg/kg dsRNA, 3.0 mg/kg dsRNA, 3.1 mg/kg dsRNA, 3.2 mg/kg dsRNA, 3.3 mg/kg dsRNA, 3.4 mg/kg dsRNA, 3.5 mg/kg dsRNA, 3.6 mg/kg dsRNA, 3.7 mg/kg dsRNA, 3.8 mg/kg dsRNA, 3.9 mg/kg dsRNA, 4.0 mg/kg dsRNA, 4.1 mg/kg dsRNA, 4.2 mg/kg dsRNA, 4.3 mg/kg dsRNA, 4.4 mg/kg dsRNA, 4.5 mg/kg dsRNA, 4.6 mg/kg dsRNA, 4.7 mg/kg dsRNA, 4.8 mg/kg dsRNA, 4.9 mg/kg dsRNA, 5.0 mg/kg dsRNA, 5.1 mg/kg dsRNA, 5.2 mg/kg dsRNA, 5.3 mg/kg dsRNA, 5.4 mg/kg dsRNA, 5.5 mg/kg dsRNA, 5.6 mg/kg dsRNA, 5.7 mg/kg dsRNA, 5.8 mg/kg dsRNA, 5.9 mg/kg dsRNA, 6.0 mg/kg dsRNA, 6.1 mg/kg dsRNA, 6.2 mg/kg dsRNA, 6.3 mg/kg dsRNA, 6.4 mg/kg dsRNA, 6.5 mg/kg dsRNA, 6.6 mg/kg dsRNA, 6.7 mg/kg dsRNA, 6.8 mg/kg dsRNA, 6.9 mg/kg dsRNA, 7.0 mg/kg dsRNA, 7.1 mg/kg dsRNA, 7.2 mg/kg dsRNA, 7.3 mg/kg dsRNA, 7.4 mg/kg dsRNA, 7.5 mg/kg dsRNA, 7.6 mg/kg dsRNA, 7.7 mg/kg dsRNA, 7.8 mg/kg dsRNA, 7.9 mg/kg dsRNA, 8.0 mg/kg dsRNA, 8.1 mg/kg dsRNA, 8.2 mg/kg dsRNA, 8.3 mg/kg dsRNA, 8.4 mg/kg dsRNA, 8.5 mg/kg dsRNA, 8.6 mg/kg dsRNA, 8.7 mg/kg dsRNA, 8.8 mg/kg dsRNA, 8.9 mg/kg dsRNA, 9.0 mg/kg dsRNA, 9.1 mg/kg dsRNA, 9.2 mg/kg dsRNA, 9.3 mg/kg dsRNA, 9.4 mg/kg dsRNA, 9.5 mg/kg dsRNA, 9.6 mg/kg dsRNA, 9.7 mg/kg dsRNA, 9.8 mg/kg dsRNA, 9.9 mg/kg dsRNA, 9.0 mg/kg dsRNA, 10 mg/kg dsRNA, 15 mg/kg dsRNA, 20 mg/kg dsRNA, 25 mg/kg dsRNA, 30 mg/kg dsRNA, 35 mg/kg dsRNA, 40 mg/kg dsRNA, 45 mg/kg dsRNA, 또는 약 50 mg/kg dsRNA를 투여받을 수 있다. 일 실시형태에서, 대상체는 0.5 mg/kg의 dsRNA를 투여받을 수 있다. 인용된 값의 중간에 있는 값 및 범위도 본 발명의 일부인 것으로 의도된다.
RNAi의 투여는 예를 들어, 환자의 세포, 조직, 혈액, 소변 또는 다른 구획에서의 PNPLA3 단백질 수준의 존재를 적어도 약 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 적어도 약 99% 이상 감소시킬 수 있다.
전체 용량의 RNAi를 투여하기 전에, 환자는 5% 주입과 같은 더 적은 용량을 투여받을 수 있고, 알레르기 반응과 같은 부작용을 모니터링할 수 있다. 또 다른 실시예에서, 환자는 증가된 사이토카인(예를 들어, TNF-알파 또는 INF-알파) 수준과 같은 원하지 않는 면역자극 효과를 모니터링할 수 있다.
PNPLA3 발현에 대한 억제 효과로 인해, 본 발명에 따른 조성물 또는 이로부터 제조된 약제학적 조성물은 삶의 질을 향상시킬 수 있다.
본 발명의 RNAi는 "네이키드(naked)"형태로 투여될 수 있으며, 여기서 변형된 또는 변형되지 않은 RNAi 작용제는 "유리 RNAi"로서 수성 또는 적합한 완충 용매에 직접 현탁된다. 유리 RNAi는 약제학적 조성물의 부재하에서 투여된다. 유리 RNAi는 적합한 완충 용액에 존재할 수 있다. 완충 용액은 아세테이트, 시트레이트, 프롤라민, 카보네이트 또는 포스페이트, 또는 이들의 임의의 조합을 포함할 수 있다. 일 실시형태에서, 완충 용액은 포스페이트 완충 식염수(PBS)이다. RNAi를 함유하는 완충 용액의 pH 및 삼투압은 대상체에게 투여하기에 적합하도록 조정될 수 있다.
대안적으로, 본 발명의 RNAi는 dsRNA 리포좀 제형과 같은 약제학적 조성물로서 투여될 수 있다.
PNPLA3 유전자 발현의 감소 및/또는 억제로부터 이익을 얻을 수 있는 대상체는 본원에 기술된 바와 같은 비알코올성 지방간 질환(NAFLD) 및/또는 PNPLA3-관련 질환 또는 장애를 갖는 대상체이다.
PNPLA3 유전자 발현의 감소 및/또는 억제로부터 이익을 얻는 대상체의 치료는 치료적 및 예방적 치료를 포함한다.
본 발명은 다른 약제학적 및/또는 다른 치료적 방법들, 예를 들어 공지된 약제학적 및/또는 공지된 치료적 방법들, 예컨대, 예를 들어, 상기 장애를 치료하기 위해 통상적으로 사용되는 방법들과 조합하여, PNPLA3 유전자 발현의 감소 및/또는 억제로부터 이익을 얻는 대상체, 예를 들어, PNPLA3-관련 질환을 갖는 대상체를 치료하기 위한 방법 및 RNAi 작용제 또는 이의 약제학적 조성물의 용도를 추가로 제공한다.
예를 들어, 특정 실시형태에서, PNPLA3 유전자를 표적화하는 RNAi는 예를 들어, 본원의 다른 곳에 기재된 바와 같은 PNPLA3-관련 질환을 치료하는데 유용한 작용제와 조합하여 투여된다. 예를 들어, PNPLA3 발현 감소로부터 이익을 얻는 대상체, 예를 들어, PNPLA3-관련 질환을 갖는 대상체를 치료하는데 적합한 추가의 치료제 및 치료 방법은 PNPLA3 유전자의 다른 부분을 표적화하는 RNAi 작용제, PNPLA3-관련 질환을 치료하기 위한 치료제, 및/또는 과정 또는 이들의 임의의 조합을 포함한다.
특정 실시형태에서, PNPLA3 유전자를 표적화하는 제1 RNAi 작용제는 PNPLA3 유전자의 다른 부분을 표적화하는 제2 RNAi 작용제와 조합하여 투여된다. 예를 들어, 제1 RNAi 작용제는 이중 가닥 영역을 형성하는 제1 센스 가닥 및 제1 안티센스 가닥을 포함하며, 여기서 상기 제1 센스 가닥의 실질적으로 모든 뉴클레오티드 및 제1 안티센스 가닥의 실질적으로 모든 뉴클레오티드는 변형된 뉴클레오티드이며, 상기 제1 센스 가닥은 3'-말단에 부착된 리간드에 접합되며, 상기 리간드는 2가 또는 3가 분지된 링커를 통해 부착된 하나 이상의 GalNAc 유도체이며; 제2 RNAi 작용제는 이중 가닥 영역을 형성하는 제2 센스 가닥 및 제2 안티센스 가닥을 포함하며, 여기서 제2 센스 가닥의 실질적으로 모든 뉴클레오티드 및 제2 안티센스 가닥의 실질적으로 모든 뉴클레오티드는 변형된 뉴클레오티드이며, 제2 센스 가닥은 3'-말단에 부착된 리간드에 접합되며, 상기 리간드는 2가 또는 3가 분지된 링커를 통해 부착된 하나 이상의 GalNAc 유도체이다.
일 실시형태에서, 제1 및 제2 센스 가닥의 모든 뉴클레오티드 및/또는 제1 및 제2 안티센스 가닥의 모든 뉴클레오티드는 변형을 포함한다.
일 실시형태에서, 변형된 뉴클레오티드 중 적어도 하나는 3'-말단 데옥시-타이민 (dT) 뉴클레오티드, 2'-0-메틸 변형된 뉴클레오티드, 2'-플루오로 변형된 뉴클레오티드, 2'-데옥시-변형된 뉴클레오티드, 잠금된 뉴클레오티드, 잠금해제된 뉴클레오티드, 입체형태적으로 제한된 뉴클레오티드, 제약된 에틸 뉴클레오티드, 비염기성 뉴클레오티드, 2'-아미노-변형된 뉴클레오티드, 2'-O-알릴-변형된 뉴클레오티드, 2'-C-알킬-변형된 뉴클레오티드, 2'-히드록슬리(hydroxly)-변형된 뉴클레오티드, 2'-메톡시에틸 변형된 뉴클레오티드, 2'-0-알킬-변형된 뉴클레오티드, 모르폴리노 뉴클레오티드, 포스포라미데이트, 비-천연 염기 포함 뉴클레오티드, 테트라히드로피란 변형된 뉴클레오티드, 1,5-안히드로헥시톨 변형된 뉴클레오티드, 시클로헥세닐 변형된 뉴클레오티드, 포스포로티오에이트 기를 포함하는 뉴클레오티드, 메틸포스포네이트 기를 포함하는 뉴클레오티드, 5'-포스페이트를 포함하는 뉴클레오티드, 및 5'-포스페이트 모방체를 포함하는 뉴클레오티드로 구성된 군으로부터 선택된다.
특정 실시형태에서, PNPLA3 유전자를 표적화하는 제1 RNAi 작용제는 PNPLA3 유전자와 상이한 유전자를 표적화하는 제2 RNAi 작용제와 조합하여 투여된다. 예를 들어, PNPLA3 유전자를 표적화하는 RNAi 작용제는 SCAP 유전자를 표적화하는 RNAi 작용제와 조합하여 투여될 수 있다. PNPLA3 유전자를 표적화하는 제1 RNAi 작용제 및 PNPLA3 유전자와 상이한 유전자, 예를 들어 SCAP 유전자를 표적화하는 제2 RNAi 작용제는 동일한 약제학적 조성물의 일부로서 투여될 수 있다. 대안적으로, PNPLA3 유전자를 표적화하는 제1 RNAi 작용제 및 PNPLA3 유전자와 상이한 유전자, 예를 들어 SCAP 유전자를 표적화하는 제2 RNAi 작용제는 상이한 약제학적 조성물의 일부로서 투여될 수 있다.
RNAi 작용제 및 추가의 치료제 및/또는 치료는 동시에 및/또는 동일한 조합으로, 예를 들어, 비경구로 투여될 수 있으며, 또는 추가의 치료제는 별개의 조성물의 일부로서 또는 별개의 시간에 및/또는 당 업계에 공지되거나 본원에 기재된 또 다른 방법에 의해 투여될 수 있다.
본 발명은 또한 세포에서 PNPLA3 발현을 감소 및/또는 억제하기 위해 본 발명의 RNAi 작용제 및/또는 본 발명의 RNAi 작용제를 함유하는 조성물을 사용하는 방법을 제공한다. 다른 양태에서, 본 발명은 세포에서 PNPLA3 유전자 발현을 감소시키고/감소시키거나 억제하는데 사용하기 위한 본 발명의 RNAi 및/또는 본 발명의 RNAi를 포함하는 조성물을 제공한다. 또 다른 양태에서, 세포에서 PNPLA3 유전자 발현을 감소시키고/감소시키거나 억제하기 위한 의약의 제조를 위한 본 발명의 RNAi 및/또는 본 발명의 RNAi를 포함하는 조성물의 용도가 제공된다. 또 다른 양태에서, 본 발명은 세포에서 PNPLA3 단백질 생성을 감소시키고/감소시키거나 억제하는데 사용하기 위한 본 발명의 RNAi 및/또는 본 발명의 RNAi를 포함하는 조성물을 제공한다. 또 다른 양태에서, 세포에서 PNPLA3 단백질 생성을 감소시키고/감소시키거나 억제하기 위한 의약의 제조를 위한 본 발명의 RNAi 및/또는 본 발명의 RNAi를 포함하는 조성물의 용도가 제공된다. 방법 및 용도는 세포를 본 발명의 RNAi, 예를 들어 dsRNA와 접촉시키고, PNPLA3 유전자의 mRNA 전사체의 분해를 수득하기에 충분한 시간 동안 세포를 유지시켜 PNPLA3 유전자의 발현을 억제하거나 세포내 PNPLA3 단백질 생성을 억제하는 것을 포함한다.
유전자 발현의 감소는 당해 분야에 공지된 임의의 방법에 의해 평가될 수 있다. 예를 들어, PNPLA3의 발현 수준의 감소는 당업자에게 일상적인 방법, 예를 들어, 노던 블롯팅, qRT-PCR을 사용하여 PNPLA3의 mRNA 발현 수준을 결정함으로써, 당업자에게 일상적인 방법, 예컨대 웨스턴 블롯팅, 면역학적 기술, 유세포 분석법, ELISA를 사용하여 PNPLA3의 단백질 수준을 결정하고/결정하거나 PNPLA3의 생물학적 활성을 결정함으로써 결정될 수 있다.
본 발명의 방법 및 용도에서, 세포는 시험관내 또는 생체내에서 접촉될 수 있으며, 즉 세포는 대상체 내에 있을 수 있다.
본 발명의 방법을 사용하여 치료하기에 적합한 세포는 PNPLA3 유전자를 발현하는 임의의 세포, 예를 들어 NAFLD를 갖는 대상체의 세포 또는 PNPLA3 유전자 또는 PNPLA3 유전자의 일부를 포함하는 발현 벡터를 포함하는 세포일 수 있다. 본 발명의 방법 및 용도에 사용하기에 적합한 세포는 포유동물 세포, 예를 들어, 영장류 세포(예컨대 인간 세포 또는 비-인간 영장류 세포, 예를 들어, 원숭이 세포 또는 침팬지 세포), 비-영장류 세포(예컨대 소 세포, 돼지 세포, 낙타 세포, 라마 세포, 말 세포, 염소 세포, 토끼 세포, 양 세포, 햄스터, 기니피그 세포, 고양이 세포, 개 세포, 래트 세포, 마우스 세포, 사자 세포, 호랑이 세포, 곰 세포, 또는 버팔로 세포), 조류 세포 (예를 들어, 오리 세포 또는 거위 세포), 또는 고래 세포일 수 있다. 일 실시형태에서, 세포는 인간 세포이다.
PNPLA3 유전자 발현은 세포에서 적어도 약 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 또는 약 100% 억제될 수 있다.
PNPLA3 단백질 생성은 세포에서 적어도 약 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 또는 약 100% 억제될 수 있다.
본 발명의 생체내 방법 및 용도는 대상체에게 RNAi를 함유하는 조성물을 투여하는 것을 포함할 수 있으며, 여기서 RNAi는 치료되는 포유동물의 PNPLA3 유전자의 RNA 전사체의 적어도 일부에 대해 상보적인 뉴클레오티드 서열을 포함한다. 치료될 유기체가 인간인 경우, 조성물은 두개 내(예를 들어, 뇌실 내, 뇌실질 내 및 경막 내), 근육 내, 경피, 기도(에어로졸), 코, 직장 및 국소(협측 및 설하 포함) 투여를 포함하는, 피하, 정맥 내, 경구, 복강 내 또는 비경구 경로를 포함하지만 이에 제한되지 않는 당 업계에 공지된 임의의 수단에 의해 투여될 수 있다. 특정 실시형태에서, 조성물은 피하 또는 정맥내 주입 또는 주사에 의해 투여될 수 있다. 일 실시형태에서, 조성물은 피하 주사에 의해 투여된다.
일부 실시형태에서, 투여는 데포 주사(depot injection)를 통해 이루어진다. 데포 주사는 장기간에 걸쳐 일정한 방식으로 RNAi를 방출할 수 있다. 따라서, 데포 주사는 원하는 효과, 예를 들어, PNPLA3의 원하는 억제, 또는 치료 또는 예방 효과를 얻기 위해 필요한 투여 빈도를 감소시킬 수 있다. 데포 주사는 또한 보다 일정한 혈청 농도를 제공할 수 있다. 데포 주사는 피하 주사 또는 근육 내 주사를 포함할 수 있다. 바람직한 실시형태에서, 데포 주사는 피하 주사이다.
일부 실시형태에서, 투여는 펌프를 통해 이루어진다. 펌프는 외부 펌프 또는 외과적으로 이식된 펌프일 수 있다. 특정 실시형태에서, 펌프는 피하 이식된 삼투 펌프이다. 다른 실시형태에서, 펌프는 주입 펌프이다. 정맥 내, 피하, 동맥 또는 경막 외 주입에 주입 펌프가 사용될 수 있다. 바람직한 실시형태에서, 주입 펌프는 피하 주입 펌프이다. 다른 실시형태에서, 펌프는 RNAi를 대상체에게 전달하는 외과적으로 이식된 펌프이다.
투여 방식은 국소 또는 전신 치료가 바람직한지 여부 및 치료될 영역에 기초하여 선택될 수 있다. 투여 경로 및 부위는 표적화를 향상시키기 위해 선택될 수 있다.
일 양태에서, 본 발명은 또한 포유동물, 예를 들어 인간에서 PNPLA3 유전자의 발현을 억제하는 방법을 제공한다. 본 발명은 또한 포유동물에서 PNPLA3 유전자의 발현을 억제하는데 사용하기 위해 포유동물의 세포에서 PNPLA3 유전자를 표적화하는 RNAi, 예를 들어 dsRNA를 포함하는 조성물을 제공한다. 또 다른 양태에서, 본 발명은 포유동물에서 PNPLA3 유전자의 발현을 억제하기 위한 의약의 제조시 포유동물의 세포에서 PNPLA3 유전자를 표적화하는 RNAi, 예를 들어 dsRNA의 용도를 제공한다.
방법 및 용도는 포유동물의 세포에서 PNPLA3 유전자를 표적화하는 RNAi, 예를 들어 dsRNA를 포함하는 조성물을 포유동물, 예를 들어 인간에게 투여하고, PNPLA3 유전자의 mRNA 전사체의 분해를 수득하기에 충분한 시간 동안 포유동물을 유지시켜, 포유동물에서 PNPLA3 유전자의 발현을 억제하는 것을 포함한다.
유전자 발현의 감소는 당 업계에 공지된 임의의 방법, 예를 들어 본원에 기재된 qRT-PCR에 의해 RNAi-투여된 대상체의 말초 혈액 샘플에서 평가될 수 있다. 단백질 생산의 감소는 당 업계에 공지된 임의의 방법 및 본원에 기재된 방법, 예를 들어 ELISA 또는 웨스턴 블롯팅에 의해 평가될 수 있다. 일 실시형태에서, 조직 샘플은 PNPLA3 유전자의 감소 및/또는 단백질 발현을 모니터링하기 위한 조직 물질로서 기능한다. 또 다른 실시형태에서, 혈액 샘플은 PNPLA3 유전자의 감소 및/또는 단백질 발현을 모니터링하기 위한 조직 물질로서 기능한다.
일 실시형태에서, RNAi 작용제 투여 후 생체내 표적의 RISC 약용된 절단의 검증은 당 업계에 공지된 프로토콜의 5'-RACE 또는 변형을 수행함으로써 수행된다(Lasham A et al., (2010) Nucleic Acid Res., 38 (3) p-el9) (Zimmermann et al. (2006) Nature 441: 111-4).
본원에 개시된 모든 리보핵산 서열은 서열에서 우라실 염기를 타이민 염기로 치환함으로써 데옥시리보핵산 서열로 전환될 수 있는 것으로 이해된다. 마찬가지로, 본원에 개시된 모든 데옥시리보핵산 서열은 서열에서 타이민 염기를 우라실 염기로 치환함으로써 리보핵산 서열로 전환될 수 있다. 데옥시리보핵산 서열, 리보핵산 서열, 및 본원에 개시된 모든 서열의 데옥시리보뉴클레오티드 및 리보뉴클레오티드의 혼합물을 함유하는 서열이 본 발명에 포함된다.
추가로, 본원에 개시된 임의의 핵산 서열은 화학적 변형의 임의의 조합으로 변형될 수 있다. 당업자는 변형된 폴리뉴클레오티드를 기술하기 위한 "RNA" 또는 "DNA"와 같은 명칭이 특정 경우 임의적이라는 것을 쉽게 이해할 것이다. 예를 들어, 리보스 당 위에 2'-OH 치환기를 갖는 뉴클레오티드 및 타이민 염기를 포함하는 폴리뉴클레오티드는 변형된 당(DNA의 천연 2'-H에 대해 2'-OH)을 갖는 DNA 분자로서 또는 변형된 염기(RNA의 천연 우라실을 위한 타이민(메틸화된 우라실))를 갖는 RNA 분자로서 기재될 수 있다.
따라서, 서열 목록의 것들을 포함하지만 이에 제한되지 않는 본원에 제공된 핵산 서열은 변형된 핵염기를 갖는 이러한 핵산을 포함하지만 이에 제한되지 않는 천연 또는 변형된 RNA 및/또는 DNA의 임의의 조합을 함유하는 핵산을 포함하는 것으로 의도된다. 추가의 예로서 비제한적으로, 서열 "ATCGATCG"를 갖는 폴리뉴클레오티드는 변형 또는 비 변형이든 간에, RNA 염기를 포함하는 상기 화합물, 예컨대 서열 "AUCGAUCG"를 갖는 화합물 및 일부 DNA 염기 및 일부 RNA 염기 예컨대 "AUCGATCG"를 갖는 화합물을 포함하지만 이에 제한되지 않는, 상기 서열을 갖는 임의의 폴리뉴클레오티드 및 다른 변형된 염기, 예컨대 "ATmeCGAUCG"를 갖는 폴리뉴클레오티드를 포함하며, 여기서 meC는 5-위치에 메틸 기를 포함하는 시토신 염기를 나타낸다.
수행된 실험 및 달성된 결과를 포함하는 하기 실시예는 단지 예시적 목적을 위해 제공되며 첨부되는 청구범위의 범위를 제한하는 것으로 간주되어서는 안 된다.
참조에 의한 통합
본 명세서에서 언급된 모든 공보, 특허 및 특허 출원은 각각의 개별 공보, 특허 또는 특허 출원이 구체적이고 개별적으로 참조로 포함된 것으로 표시되는 것과 동일한 정도로 본원에 참조로 포함된다. 그러나, 본 명세서에서 참고문헌의 인용은 그러한 참고문헌이 본 발명의 선행 기술이라는 인정으로 해석되어서는 안된다. 참조로 포함된 참고 문헌에 제공된 임의의 정의 또는 용어가 본원에 제공된 용어 및 논의와 상이할 경우, 본 용어 및 정의를 우선시한다.
등가물
전술한 명세서는 당업자가 본 발명을 실시할 수 있도록 충분한 것으로 간주된다. 전술한 설명 및 예는 본 발명의 특정 바람직한 실시형태를 상세히 설명하고 본 발명자들이 고려한 최상의 모드를 설명한다. 그러나, 전술한 내용이 텍스트로 상세하게 기재되었을지라도, 본 발명은 많은 방식으로 실시될 수 있으며 본 발명은 첨부된 청구범위 및 그의 임의의 등가물에 따라 해석되어야 한다는 것이 이해될 것이다.
수행된 실험 및 달성된 결과를 포함하는 하기 실시예는 단지 예시적 목적을 위해 제공되며 본 발명을 제한하는 것으로 간주되어서는 안 된다.
실시예 1: 변형된 PNPLA3 siRNA 분자의 선택, 설계 및 합성
파타틴-유사 포스포리파제 도메인-함유 3(PNPLA3)을 표적화하는 치료적 siRNA 분자에 대한 최적의 서열의 확인 및 선택은 인간 PNPLA3 전사체(NM_025225.2)의 생물정보학 분석을 사용하여 확인하였다. 표 1은 치료적 특성을 갖는 것으로 확인된 서열을 보여준다. 다양한 서열에서, {INVAB}는 역전된 A 염기성이고, {INVDA}는 역전된 데옥시티미딘이고, GNA는 글리콜 핵산이고, dT는 데옥시티미딘이고, dC는 데옥시시토신이다.
[표 1]
PNPLA3 siRNA 서열의 효능 및 생체내 안정성을 개선시키기 위해, 화학적 변형을 PNPLA3 siRNA 분자에 포함시켰다. 구체적으로, 리보스 당의 2'-O-메틸 및 2'-플루오로 변형은 PNPLA3 siRNA 내의 특정 위치에 포함되었다. 포스포로티오에이트 뉴클레오티드간 연결은 또한 안티센스 및/또는 센스 서열의 말단에 포함되었다. 하기 표 2는 변형된 PNPLA3 siRNA의 각각에 대한 센스 및 안티센스 서열에서의 변형을 나타낸다. 표 X의 뉴클레오티드 서열은 하기 표기법에 따라 열거된다: A, U, G, 및 C = 상응하는 리보뉴클레오티드; dT = 데옥시티미딘; a, u, g, 및 c = 상응하는 2'-O-메틸 리보뉴클레오티드; Af, Uf, Gf, 및 Cf = 상응하는 2'-데옥시-2'-플루오로("2'-플루오로") 리보뉴클레오티드. 서열에서 "s"의 삽입은 2개의 인접한 뉴클레오티드가 포스포로티오디에스테르 기에 의해 연결(예를 들어, 포스포로티오에이트 뉴클레오티드간 연결)됨을 나타낸다. 달리 지시되지 않는 한, 다른 모든 뉴클레오티드는 3'-5' 포스포디에스테르 기에 의해 연결된다. 표 2의 각각의 siRNA 화합물은 양쪽 가닥의 3' 말단에 2개의 뉴클레오티드 오버행 또는 한쪽 또는 양쪽 말단에 블런트머를 갖는 19개의 염기쌍 이중체 영역을 포함한다. GalNAc3K2AhxC6은 하기이다:
[표 2]
실시예 2: RNA FISH 분석에서 선택된 PNPLA3 siRNA 분자의 효능
PNPLA3 중의 rs738409 및/또는 rs738408 SNP에 걸친 siRNA를 포함하는, 완전히 화학적으로 변형된 siRNA의 패널을 제조하고 시험관내에서 mRNA 녹다운의 효능 및 선택성에 대해 시험하였다. 각각의 siRNA 이중체는 센스 또는 '패신저' 가닥 및 안티센스 또는 '가이드' 가닥의 두 가닥으로 구성되어 있다. 가닥들은 19개의 상보적 염기쌍을 갖는 21개 또는 23개 뉴클레오티드 길이이다. 일부 경우에, 2개의 염기쌍 3' 오버행이 있다. siRNA는 각 뉴클레오티드의 리보스에서 천연 2'-OH를 2'-OMe 또는 2'-F 기로 치환하여 제조하였다. 선택적으로, 하나 또는 양쪽 가닥 모두에서 포스포디에스테르 뉴클레오티드간 연결을 포스포로티오에이트로 대체하여 엑소뉴클레아제에 의한 분해를 감소시킨다.
PNPLA3 발현을 감소시키는 데 있어서의 각각의 siRNA 분자의 효능을 384-웰 포맷 시험관내 siRNA 형질감염 분석에 이어서 IC50 및 최대 활성 값을 결정하기 위해 리보핵산 분자(RNA FISH) 분석을 표적화하는 형광성 인시추 하이브리드화를 이용하여 평가하였다. 이 분석은 인간 PNPLA3 I148I를 발현하는 인간 간세포 암종 세포주 Hep3B 세포(ATCC HB-8064) 및 중국 햄스터 난소(CHO) 세포에서 수행하였다. 인간 간세포 암종 HepB3을 37℃ 및 5% CO2에서 10% 소 태아 혈청 및 1% 항생제/항진균제가 보충된 EMEM 배지(ATCC 30-2003)에서 유지시켰다. 인간 PNPLA3 I148I를 발현하는 CHO 세포를 37℃ 및 5% CO2에서 50% CD-CHO를 함유하는 배지(Life Technologies), 50% Ex-Cell CHO 5 배지(Sigma), 8 mM L-글루타민, 1 × HT, 1% 항생제/항진균제, 및 10 μg/mL 푸로마이신을 함유하는 배지에서 유지시켰다.
Hep3B 세포 분석을 위해, 제조업체의 권장 사항에 따라, EMEM 배지(ATCC 30-2003) 중의 siRNA 분자 및 리포펙타민 RNAiMAX 트랜스펙션 시약(Life Technologies)의 트랜스펙션 복합체를 384-웰 플레이트(PerkinElmer)에서 웰당 10μg으로 제조하였다. CHO 인간 세포 분석을 위해, 제조업체의 권장 사항에 따라, F12K 배지(Mediatech) 중의 siRNA 분자 및 리포펙타민 RNAiMAX 트랜스펙션 시약의 트랜스펙션 복합체를 384-웰 플레이트에서 웰당 10 μg으로 제조하였다. 세포를 항생제/항진균제-비함유 배지에서 67,000 세포/ml로 희석하고, 30 μl를 각 웰에 첨가하였으며, 40 μl 배지에서 2000 세포/웰의 최종 밀도를 가졌다. 실온에서 20분 동안 인큐베이션한 후, 플레이트를 37℃ 및 5% CO2 인큐베이터로 옮겼다. Hep3B 세포 트랜스펙션 분석을 72시간 동안 인큐베이션하고, CHO 인간 PNPLA3 I148I 트랜스펙션 분석을 48시간 동안 인큐베이션하였다.
수확시, 세포를 실온에서 15분 동안 8% 포름알데히드 고정 용액(Thermo Scientific)에 고정시켰다. 이어서, 플레이트를 순차적인 50%, 70%, 및 100% 에탄올로 세척하여 탈수시켰다. 이어서 플레이트를 밀봉하고 -20℃에서 저장하였다.
RNA FISH 분석은 Affymetrix QuantiGene® View RNA HC 스크리닝 분석 키트(QVP0011), Affymetrix View HC 신호 증폭 키트 3-plex(QVP0213), 및 Affymetrix 유전자 특이적 프로브를 사용하여 수행하였다: PNPLA3 인간 0.33 mL View RNA 타입 6(650 라벨) VA6-20279-01 및 PPIB 인간 0.44 mL View RNA 타입 1(488 라벨) VA1-10148-01.
플레이트를 먼저 순차적인 100%, 70%, 및 50% 에탄올로 세척하여 재수화시켰다. 이어서, 세포를 PBS로 세척한 후, 키트 지침에 따라 투과화 및 프로테아제-소화시켰다. 표적 워킹 프로브 세트(Working Probe Set)는 제조사의 프로토콜에 따라 제조하고, 웰에 첨가하고 40℃에서 3시간 동안 배양하였다. 워킹 프로브 세트, 워킹 프리앰프(Working PreAmp), 워킹 앰프(Working Amp) 및 워킹 LP(Working LP)와의 순차적 하이브리드화를 위해 제조업체의 프로토콜을 따랐다. 마지막으로, 핵 카운터스테인(nuclei counterstain)을 적용하였다(Hoechst 33342 and Cell Mask Blue; Molecular Probes). 플레이트를 실온에서 30분 동안 인큐베이션하고, PBS로 세척하고, 80 μl의 PBS로 오버레이한 후, 플레이트를 이미징을 위해 밀봉하였다.
Hoechst 33342용 UV 채널 및 Cell Mask Blue, 타입1 프로브용 488 채널, 및 타입6 프로브에 대한 647 채널을 사용하여 Opera Phenix High Content Screening System(PerkinElmer)에서 모든 플레이트를 이미지화하였다.
콜럼버스 소프트웨어를 사용하여 RNA FISH 데이터를 분석하고, Genedata Screener를 사용하여 이미지를 생성하였다. CHO 트랜스펙션된 PNPLA3 I148I에 대한 분석 결과는 표 3에 제시되어 있다. CHO 트랜스펙션된 PNPLA3 I148M에 대한 분석 결과는 표 4에 제시되어 있다. PNPLA3 녹다운은 대조군과 비교하여 녹다운의 백분율을 제공한다. 음수 값은 PNPLA3 수준의 감소를 나타낸다.
[표 3]
[표 4]
RNA FISH는 또한 이중 돌연변이 PNPLA3-rs738408-rs738409뿐만 아니라 대조군 야생형 세포주 Hep3B를 함유하는 간 세포주에서 실행하였다. Hep3B 및 HepG2 세포(ATCC에서 구입)를 10% 소 태아 혈청(FBS, Sigma) 및 1% 페니실린-스트렙토마이신(P-S, Corning)이 보충된 최소 필수 배지(Hep3B의 경우 Corning으로부터의 MEM 및 HepG2의 경우 ATCC로부터의 EMEM)에서 배양하였다. 하기에 따라 siRNA 트랜스펙션을 수행하였다: 세포주에 따라 1 μL의 시험 siRNAs 및 4 μL의 일반 MEM 또는 EMEM을 BioMek FX(Beckman Coulter)에 의해 PDL-코팅된 CellCarrier-384 Ultra 분석 플레이트(PerkinElmer)에 첨가하였다. 일반 MEM 또는 EMEM(구체적으로, Hep3B의 경우 5 μL MEM 중의 0.035 μL RNAiMAX 및 HepG2의 경우 5 μL EMEM 중의 0.06 μL의 RNAiMAX)에 사전-희석된, 5 μL의 리포펙타민 RNAiMAX(Thermo Fisher Scientific)을 Multidrop Combi 시약 분주기(Thermo Fisher Scientific)에 의해 분석 플레이트에 분주하였다. 실온(RT)에서 siRNA/RNAiMAX 혼합물을 20분 동안 인큐베이션한 후, 10% FBS 및 1% P-S가 보충된 MEM 또는 EMEM 중의 30 μL의 Hep3B 또는 HepG2 세포(웰당 2000개 세포)를 Multidrop Combi 시약 분주기를 사용하여 트랜스펙션 복합체에 첨가하였다. 그 후 분석 플레이트를 인큐베이터에 위치시키기 전에 실온에서 20분 동안 인큐베이션하였다. 이어서, 세포를 37℃ 및 5% CO2에서 72시간 동안 인큐베이션하였다. ViewRNA ISH 세포 분석은 액체 처리를 위해 자체조립된 자동 FISH 분석 플랫폼을 사용하여 제조사의 프로토콜(Thermo Fisher Scientific)에 따라 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 쌍(Thermo Fisher Scientific)의 배양을 3시간 동안 수행한 반면, 전치 증폭기, 증폭기 및 라벨 프로브(Thermo Fisher Scientific)의 경우 각각 1시간 동안 수행하였다. 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 다음, Opera Phenix (PerkinElmer)에서 영상화하였다. 콜럼버스 이미지 데이터 저장 및 분석 시스템 (PerkinElmer)을 사용하여 이미지를 분석하여 세포 당 평균 스팟 카운트를 얻었다. 스팟 카운트는 높은(인산 완충 식염수 함유, Corning) 및 낮은(표적 프로브 쌍없음) 대조군 웰을 사용하여 정규화되었다. 총 siRNA 농도에 대한 정규화된 값을 플롯팅하고 데이터를 Genedata Screener(Genedata)의 4-파라미터 시그모이드 모델에 맞추어 IC50 및 최대 활성을 얻었다. HepG2 세포에 대한 분석 결과는 표 5에, Hep3B 세포에 대한 분석 결과는 표 6에 나타낸다. PNPLA3 녹다운은 대조군과 비교하여 녹다운의 백분율을 제공한다. 음성 값은 PNPLA3 수준의 감소를 나타낸다. 이중체가 한 번 이상 실행된 경우, 표준 편차와 함께 평균 IC50이 표시된다.
[표 5]
[표 6]
실시예 3: PNPLA3-rs738409 및 PNPLA3-rs738409-rs738408에 대한 siRNA의 액적 디지털 PCR 분석
제조사 프로토콜에 따라, OptiThaw 배지(Xenotech cat#K8000)에서 인간 1차 간세포(Xenotech/Sekisui 공여자 로트#HC3-38)를 해동시킨 후, 세포를 원심분리하고 배지 흡인 후, OptiPlate 간세포 배지(Xenotech cat#K8200)에 재현탁시키고, 96 웰 콜라겐 코팅된 플레이트(Greiner cat#655950)에 플레이팅하였다. 2~4시간 인큐베이션 기간 후, 배지를 제거하고, OptiCulture 간세포 배지(Xenotech cat#K8300)로 교체하였다. OptiCulture 배지를 첨가한 후 2~4시간 후, 자유 흡수(트랜스펙션 시약 없음)를 통해 세포에 GalNAc 접합된 siRNA를 전달하였다. 세포를 37℃ 및 5% CO2에서 24~72시간 동안 인큐베이션하였다. 이어서, 세포를 Qiagen RLT 완충액(79216) +1% 2-머캅토에탄올(Sigma, M-3148)로 용해시키고, 용해물을 -20℃에서 저장하였다. Qiagen QIACube HT 기기(9001793) 및 Qiagen RNeasy 96 QIACube HT 키트(74171)를 사용하여 제조업체의 지침에 따라 RNA를 정제하였다. QIAxpert 시스템(9002340)을 사용하여 샘플을 분석하였다. cDNA는 Applied Biosystems 고용량 cDNA 역전사 키트(4368813)를 사용하여 RNA 샘플로부터 합성되었고, 반응은 제조사의 지시에 따라 취합하였으며, 입력 RNA 농도는 샘플에 따라 다양하였다. 역전사를 하기 조건 하에서 BioRad 4중 열 사이클러(모델# PTC-0240G)에서 수행하였다: 25℃ 10분, 37℃ 120분, 85℃ 5분 후(선택적) 4℃ 무한 유지.
액적 디지털 PCR(ddPCR)은 제조사의 지시에 따라 BioRad의 QX200 AutoDG 액적 디지털 PCR 시스템을 사용하여 수행되었다. 반응은 프로브(1863010)에 대한 BioRad ddPCR Supermix를 사용하여 에펜도르프 클리어 96 웰 PCR 플레이트(951020303)에 취합하고, PNPLA3(IDT Hs.PT.58.21464637, 프라이머 대 프로브 비율 3.6:1 및 TBP(IDT Hs.PT.53a.20105486, 프라이머 대 프로브 비율 3.6:1) 및 RNase 비함유 물(Ambion, Am9937)에 대한 qPCR 분석을 형광 표지하였다. 최종 프라이머/프로브 농도는 각각 900 nM/250 nM이며, 입력 cDNA 농도는 웰마다 다양하다. 제조업체 권장 소모품(BioRad DG32 카트리지 1864108, BioRad 팁 1864121, 에펜도르프 블루 96 웰 PCR 플레이트 951020362, 프로브 1864110용 BioRad 액적 생성 오일 및 BioRad 액적 플레이트 어셈블리)로 구성된 BioRad Auto DG 액적 생성기(1864101)를 사용하여 액적이 형성되었다. 하기 조건을 사용하여 BioRad C1000 터치 열 사이클러(1851197)에서 액적을 증폭시켰다: 효소 활성화 95℃ 10분, 변성 94℃ 30초에 이어, 1분 동안 어닐링/연장 60℃, 2℃/초 램프 속도를 사용하여 40 사이클, 효소 비활성화 98℃ 10분 후(선택적) 4℃ 무한 유지. 이어서 샘플을 PNPLA3 또는 TBP 농도와 상관되는 FAM/HEX 신호를 측정하는 BioRad QX200 액적 판독기에서 판독하였다. BioRad의 QuantaSoft 소프트웨어 패키지를 사용하여 데이터를 분석했다. 샘플을 채널(형광 라벨)로 게이팅하여, 샘플 당 농도를 측정하였다. 이어서, 각 샘플은 샘플 로딩의 차이를 제어하기 위해 관심 유전자의 농도(PNPLA3)/하우스키핑 유전자(TBP)의 농도의 비율로 표현된다. 그런 다음 데이터를 Genedata Screener로 가져오며, 여기서 각 테스트 siRNA는 중성 대조군 웰의 중앙값으로 정규화된다(완충액 단독). IC50 값은 표 7에 보고되어 있다.
[표 7]
실시예 4: 인간화된 마우스 모델에서 선택된 PNPLA3 siRNA 분자의 효능 스크리닝
인산 완충 식염수(Thermo Fisher Scientific,14190-136)에서 동물 당 4e11 내지 1e12 바이러스 입자로 희석된 관련 아데노바이러스(AAV; 혈청형 AAV8 또는 AAV7; 내독소-프리, Amgen에 의해 내부적으로 제조됨)를 C57BL/6NCrl 수컷 마우스(Charles River Laboratories Inc.)의 꼬리 정맥에 정맥내 주사하여, 간에서 인간 PNPLA3 WT (PNPLA3-WT), PNPLA3 rs738409 (PNPLA3-I148M), 또는 PNPLA3 rs738409-rs738408 (PNPLA3-I148M DM)의 발현을 유도하였다. 마우스는 일반적으로 10~12주령이었으며, 그룹 당 n=4~6마리의 동물이 포함되었다. 모든 라운드의 스크리닝은 적어도 2개의 비히클-처리된 대조군 그룹들을 포함하였다: AAV-비어있는 벡터 및 AAV-PNPLA3 WT 또는 PNPLA3 rs738409 및 비히클로 처리된 PNPLA3 rs738409-rs738408 . 모든 siRNA를 AAV-PNPLA3 WT , PNPLA3 rs738409 , 및/또는 PNPLA3 rs738409-rs738408 에 대해 시험하였다. AAV 주사 2주 후, 인산 완충 식염수로 희석된 동물 킬로그램 당 0.5, 1.0, 3.0 또는 5.0 밀리그램으로 피하 주사를 통해 단일 용량의 siRNA D-2324(0.5 mM)로 마우스를 처리하였다 (Thermo Fisher Scientific,14190-136). siRNA 주사 후 8, 15, 22, 28 또는 42일에, 간을 동물로부터 수집하고, 액체 질소에서 스냅 냉동하고, 제조업체의 지침에 따라 QIACube HT 기기(Qiagen, 9001793) 및 RNeasy 96 QIACube HT 키트(Qiagen, 74171)를 사용하여 정제된 RNA에 대해 처리하였다. QIAxpert 시스템(Qiagen, 9002340)을 사용하여 샘플을 분석하였다. RNA를 RQ1 RNase-Free DNase(Promega, M6101)로 처리하고, TaqManTM RNA-to-CTTM 1-단계 키트(Applied Biosystems, 4392653)를 사용하여 실시간 qPCR을 위해 제조하였다. 실시간 qPCR은 QuantStudio 실시간 PCR 기계에서 실행되었다. 결과는 마우스 Gapdh(각각 Invitrogen으로부터의 TaqManTM 분석, hs00228747_m1 및 4352932E)에 정규화된 인간 PNPLA3의 유전자 발현을 기초로 하며, 비히클-처리된 대조군 동물과 비교하여 인간 PNPLA3 mRNA 발현의 상대적인 녹다운으로 제시된다. 내인성 마우스 Pnpla3 발현을 비교를 위해 결정하였다(Invitrogen, Mm00504420_m1).
간 트리글리세리드 함량 분석을 위해, 동물로부터의 대략 0.05~0.1 밀리그램의 냉동 간을 1 밀리리터의 이소프로판올에서 균질화시켰다. 얼음에서 1시간 동안 인큐베이션한 후, 샘플을 마이크로퓨즈에서 10,000 rpm으로 회전시키고, 상청액을 깨끗한 딥-웰 96-웰 플레이트로 옮겼다. 트리글리세리드 함량은 제조업체의 지시에 따라 비색 무한대 트리글리세리드 시약(Thermo Fisher Scientific, TR22421) 및 트리글리세리드 스탠다드(Pointe Scientific, T7531-STD)를 사용하여 측정하였다. 결과는 조직의 밀리그램 당 트리글리세리드의 밀리그램으로서 제시된다.
본원에 기술된 모든 동물 실험은 Amgen의 동물실험윤리위원회(Institutional Animal Care and Use Committee, IACUC)에 의해 승인되었고, 실험 동물의 관리 및 사용을 위한 안내서(Guide for the Care and Use of Laboratory Animals), 8th Edition (National Research Council (U.S.)에 따라 관리되었다. 실험실 동물의 관리 및 사용을 위한 가이드 업데이트 위원회(Committee for the Update of the Guide for the Care and Use of Laboratory Animals), 실험실 동물 연구를 위한 연구소(US) 및 국립 아카데미 프레스(National Academies Press)(US)(2011), 실험실 동물의 관리 및 사용을 위한 안내서. 8th Ed., National Academies Press, Washington, D.C. 12시간의 조명과 12시간의 암흑주기(0600~1800 시간)를 가진 22±2℃의 에어컨이 있는 방에 마우스를 단독 수용하였다. 달리 지시하지 않는 한 동물들은 정기적인 차우 식이 (Envigo, 2920X) 및 자동 급수 시스템을 통한 물(역삼투-정제됨)에 자유롭게 접근할 수 있었다. 종료 후, 심부 마취하에 심장 천자에 의해 혈액을 수집한 다음, 실험동물 관리평가 인증협회(Association for Assessment and Accreditation of Laboratory Animal Care, AAALAC) 가이드라인에 따라, 2차 물리적 방법으로 안락사시켰다. 도 1a~1d. 용량-의존적 mRNA 녹다운 및 생체내 기능적 내구성 둘 다에 대해 스크리닝된 5개의 siRNA 분자의 예. 인간 PNPLA3 rs738409-rs738408 을 발현하는 마우스를 정맥 내 AAV 주사 2주 후에 siRNA로 처리하였다. 그룹 당 N=6 마우스; 데이터는 평균 및 평균의 표준 오차로 표시된다. (A) siRNA를 체중 1kg 당 0.5, 1.0, 3.0, 또는 5.0 밀리그램으로 마우스의 복부에 피하 주사하였다. siRNA 처리 4주 후, 마우스를 희생시키고 간을 수집하고 유전자 발현 분석을 위해 처리하였다. 데이터는 비히클-처리된 대조군 그룹으로 설정된 각 그룹에서 인간 PNPLA3 rs738409-rs738408 의 평균 상대 녹다운을 나타낸다. (B) 동일한 4주 처리 그룹의 간을 또한 트리글리세리드 함량에 대해 처리하여 기능적 효능에 접근하였다. 데이터는 처리된 조직 그램 당 트리글리세리드의 평균 밀리그램을 나타낸다. (C) siRNA를 체중의 kg 당 1.0 및 3.0 밀리그램으로 동물의 평행 코호트의 복부에 피하 주사하였다. siRNA 처리 6주 후에 마우스를 수확하여 생체내에서 siRNA 분자의 내구성을 비교하였다. 간은 유전자 발현 분석을 위해 수집되고 처리되었다. 데이터는 비히클-처리된 대조군 그룹으로 설정된 각 그룹에서 인간 PNPLA3 rs738409-rs738408 의 평균 상대 녹다운을 나타낸다. (D) 동일한 6주 처리 그룹의 간을 또한 트리글리세리드 함량에 대해 처리하여 시간 경과에 따른 기능적 효능에 접근하였다. 데이터는 처리된 조직 그램 당 트리글리세리드의 평균 밀리그램을 나타낸다.
상대 녹다운에 대한 데이터는 표 8~12에 제시되어 있으며, 8, 15, 22, 28, 및 42일 각각의 상대 녹다운 및 다양한 용량을 나타낸다. PNPLA3 녹다운은 백분율이며, 음수 값은 PNPLA3 수준의 감소를 나타낸다.
[표 8]
[표 9]
[표 10]
[표 11]
[표 12]
실시예 5: 인간화된
PNPLA3
rs738409-rs738408
마우스 모델에서 siRNA 분자에 의한 NAFLD의 예방 및 구제
'아메리칸 라이프스타일-유도 비만 증후군', 또는 NAFLD/NASH에 대한 ALIOS 마우스 모델은 트랜스-지방(총 지방량의 45%) 및 당이 많은 식이를 마우스에 공급함으로써 개발된다 (Tetri 2008). 이들 연구를 위해, 8 내지 10주령의 C57BL/6NCrl 수컷 마우스 (Charles River Laboratories Inc.)에 전술한 바와 같이 AAV-비어있는 벡터 또는 AAV8-PNPLA3 rs738409-rs738408 을 주사하였다. AAV 주사시, 마우스는 정상 차우식으로 유지되거나, 수확때까지, 식수와 함께 55% 프룩토스 및 45% 글루코스 (각각 Sigma, F0127 및 G7021)로 구성된 ALIOS 식이 (Envigo, TD.06303)에 두었다. 이전 실험에서, 이러한 맥락에서 PNPLA3rs738409-rs738408의 과발현은 NAFLD 표현형을 가속화하고 악화시킨다는 것이 밝혀졌다 (데이터는 나타내지 않음).
AAV 주사 및 식이 개시 2주 후, 인산 완충 식염수로 희석된 동물 킬로그램 당 5.0 밀리그램으로 피하 주사를 통해 단일 용량의 siRNA D-2324(0.5 mM)로 마우스를 처리하거나 (Thermo Fisher Scientific,14190-136), 비히클 대조군으로 처리하였다. 수확까지 2주마다 투여를 반복하였다. 수확 시점에, 체중을 수집한 후, 이소플루란 마취하에 심장 천자를 통한 혈청, 이어서 간 중량을 수집하였다. 중간엽은 10% 중성 완충 포르말린을 통해 고정된 후 파라핀 가공 및 임베딩(embedding)을 하였다. 전술한 바와 같이, 나머지 간을 내용물 및 유전자 발현 분석을 위해 스냅 냉동시켰다.
스냅 냉동된 간 조직을 전술한 바와 같이 RNA 및 유전자 발현 분석을 위해 처리하였다. 결과는 마우스 Gapdh에 대해 표준화된 지시된 유전자의 원시 Ct 값 및 상대 mRNA 발현 둘 모두로서 제시된다(Invitrogen으로부터의 TaqManTM 분석: 인간 PNPLA3, hs00228747_m1; 마우스 Pnpla3, Mm00504420_m1; 마우스 Gapdh, 4352932E).
포르말린-고정된 조직은 제조사의 지시에 따라 헤모톡실린 및 에오신 염색(각각 Dako, CS70030-2, CS70130-2)을 위해 처리되었다. 지방증 및 염증에 대한 점수는 협회-인증 병리학자에 의해 수행되었다.
혈청 분석은 NASH 및 NASH-관련 섬유증과 관련된 바이오마커인 TIMP1을 포함하였다(Youssani 2011). TIMP1 ELISA (R&D Systems, MTM100)는 제조업체의 지침에 따라 수행되었다.
도 2a~g. NAFLD와 관련된 표현형의 발달 및 PNPLA3 rs738409-rs738408 의 과발현을 예방하는 PNPLA3rs738409-rs738408 - 특이적 siRNA 분자 D-2324의 능력을 평가하기 위해, 마우스는 AAV8-비어있는 벡터(EV), 또는 AAV8-PNPLA3 rs738409-rs738408 , 또는 비히클을 제공받거나, 규칙적인 차우식으로 유지되거나, 또는 ALIOS 식이로 전환되었다. AAV 주사 2주 후, 마우스를 6주 동안 격주로 siRNA 또는 비히클로 처리하였다; 총 3회의 주사 라운드. 8주 시점에 마우스를 수확하였다. 결과는 그룹 평균 및 표준 오차, 그룹당 N=8로 표시된다. 별표는 Dunnett의 다중 비교 테스트를 사용하는 일원 분산 분석(One-way ANOVA)에 의해 생성된 AAV8-PNPLA3 rs738409-rs738408 코호트에 대한 통계적 유의성을 나타낸다. (A) 수확시 간 중량(그램) 대 체중(그램)의 비. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, **=0.0018, AAV- PNPLA3 rs738409-rs738408 + siRNA, ****<0.0001. (B) qPCR에 의한 간에서의 인간 PNPLA3 mRNA 발현 및 사일런싱의 확인. (왼쪽) 원시 Ct 값 및 (오른쪽) 마우스 Gapdh에 대해 정규화된 상대 폴드 mRNA 발현; ALIOS-공급된 PNPLA3 rs738409-rs738408 + 비히클 및 PNPLA3 rs738409-rs738408 + siRNA 그룹 비교. (C) qPCR에 의한 간에서의 마우스 Pnpla3 mRNA 발현의 분석은 내인성 Pnpla3이 AAV-매개된 과-발현 또는 siRNA 사일런싱에 의해 크게 변경되지 않음을 나타낸다. (왼쪽) 원시 Ct 값 및 (오른쪽) 마우스 Gapdh에 대해 정규화된 상대 폴드 mRNA 발현; 차우-공급된 무-AAV 그룹을 ALIOS-공급된 PNPLA3 rs738409-rs738408 + 비히클 및 PNPLA3 rs738409-rs738408 + siRNA 그룹과 비교. (D) 간 트리글리세리드 함량은 간 조직 1 g 당 트리글리세리드 밀리그램으로 제시되었다. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, *=0.0393, AAV- PNPLA3 rs738409-rs738408 + siRNA, **=0.0063. (E) 혈청 TIMP1은 혈청 1 밀리리터 당 피코그램으로 제시되었다. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, ****<0.0001, AAV- PNPLA3 rs738409-rs738408 + siRNA, ****<0.0001. (F) H&E 염색에 기초한 지방증의 조직학적 표시는 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, 유의미하지 않음, AAV- PNPLA3 rs738409-rs738408 + siRNA, **=0.0012. (G) H&E 염색에 기초한 염증의 조직학적 표시는 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, ****<0.0001, AAV- PNPLA3 rs738409-rs738408 + siRNA, ****<0.0001.
도 3a-g. 질환 발병 후 PNPLA3rs738409-rs738408-매개된 질환의 추가 진행을 예방하는 PNPLA3rs738409-rs738408 - 특이적 siRNA 분자의 능력을 평가하기 위해, 마우스는 AAV8-비어있는 벡터 (EV), 또는 AAV8-PNPLA3 rs738409-rs738408 , 또는 비히클을 제공았으며, 규칙적인 차우식으로 유지되거나, 또는 ALIOS 식이로 전환되었다. AAV 주사 및 식이 변화 8주 후, 마우스를 추가 8주 동안 격주로 siRNA 또는 비히클로 처리하였다; 총 4회의 주사 라운드. 16주 시점에 마우스를 수확하였다. 지방증에서 변화는 관찰되지 않았지만, 질환 유도 후 siRNA 치료가 시작되면, 다른 여러 질환-관련 종말점이 크게 감소했다. 결과는 평균 및 표준 오차, 그룹당 N=8로 표시된다. 별표는 Dunnett의 다중 비교 테스트를 사용하는 일원 분산 분석(One-way ANOVA)에 의해 생성된 AAV8-PNPLA3 rs738409-rs738408 코호트에 대한 통계적 유의성을 나타낸다. (A) 수확시 간 중량 (그램) 대 체중 (그램)의 비. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, 유의미하지 않음, AAV- PNPLA3 rs738409-rs738408 + siRNA, ***=0.0006. (B) qPCR에 의한 간에서의 인간 PNPLA3 mRNA 발현 및 사일런싱의 확인. (왼쪽) 원시 Ct 값 및 (오른쪽) 마우스 Gapdh에 대해 정규화된 상대 폴드 mRNA 발현; ALIOS-공급된 PNPLA3 rs738409-rs738408 + 비히클 및 PNPLA3 rs738409-rs738408 + siRNA 그룹 비교. (C) qPCR에 의한 간에서의 마우스 Pnpla3 mRNA 발현의 분석은 내인성 Pnpla3이 AAV-매개된 과-발현 또는 siRNA 사일런싱에 의해 크게 변경되지 않음을 나타낸다. (왼쪽) 원시 Ct 값 및 (오른쪽) 마우스 Gapdh에 대해 정규화된 상대 폴드 mRNA 발현; 차우-공급된 무-AAV 그룹을 ALIOS-공급된 PNPLA3 rs738409-rs738408 + 비히클 및 PNPLA3 rs738409-rs738408 + siRNA 그룹과 비교. (D) 간 트리글리세리드 함량은 간 조직 1g 당 트리글리세리드 밀리그램으로 제시되었다. 조정된 P 값: AAV-EV + 비히클, 유의미하지 않음, AAV- PNPLA3 rs738409-rs738408 + siRNA, *=0.0403. (E) 혈청 TIMP1은 혈청 1 밀리리터 당 피코그램으로 제시되었다. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, **=0.0027, AAV- PNPLA3 rs738409-rs738408 + siRNA, **=0.002. (F) H&E 염색에 기초한 지방증의 조직학적 표시는 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, 유의미하지 않음, AAV- PNPLA3 rs738409-rs738408 + siRNA, 유의미하지 않음. (G) H&E 염색에 기초한 염증의 조직학적 표시는 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, 유의미하지 않음, AAV- PNPLA3 rs738409-rs738408 + siRNA, **=0.0068.
도 4a~d. PNPLA3rs738409-rs738408의 과발현으로 인한 질환-관련 표현형을 구제하는 PNPLA3rs738409-rs738408 - 특이적 siRNA 분자의 능력을 평가하기 위해, ALIOS-공급된 8주 AAV8-PNPLA3 rs738409-rs738408 -비히클 처리된 마우스로부터의 간 및 혈청을 ALIOS-공급된 16주 비히클- 또는 siRNA-처리된 AAV8-PNPLA3 rs738409-rs738408 마우스로부터의 간 및 혈청과 비교하였다. siRNA 처리로 이 시점에서 지방증에서 변화가 관찰되지 않았지만, 간 트리글리세리드, 혈청 TIMP1 및 염증은 8주에서의 비히클 대조군과 비교하여 16주에서 통계적으로 모두 낮았다. 결과는 평균 및 표준 오차, 그룹당 N=8로 표시된다. 별표는 Dunnett의 다중 비교 테스트를 사용하는 일원 분산 분석(One-way ANOVA)에 의해 생성된 8주 AAV8-PNPLA3 rs738409-rs738408 비히클-처리된 코호트에 대한 통계적 유의성을 나타낸다. (A) 간 트리글리세리드 함량은 간 조직 1g 당 트리글리세리드 밀리그램으로 제시되었다. 조정된 P 값: 16주 AAV- PNPLA3 rs738409-rs738408 + 비히클, 유의미하지 않음; 16주 AAV- PNPLA3 rs738409-rs738408 + siRNA, **=0.0011. (B) 혈청 Timp1은 혈청 1 밀리리터 당 피코그램으로 제시되었다. 조정된 P 값: 16주 AAV- PNPLA3 rs738409-rs738408 + 비히클, 유의미하지 않음; 16주 AAV- PNPLA3 rs738409-rs738408 + siRNA, *=0.0134. (C) H&E 염색에 기초한 지방증의 조직학적 표시는 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: 16주 AAV- PNPLA3 rs738409-rs738408 + 비히클, 유의미하지 않음; 16주 AAV- PNPLA3 rs738409-rs738408 + siRNA, 유의미하지 않음. (D) H&E 염색에 기초한 염증의 조직학적 표시는 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: 16주 AAV- PNPLA3 rs738409-rs738408 + 비히클, 유의미하지 않음; 16WK AAV- PNPLA3 rs738409-rs738408 + siRNA, *=0.0112.
실시예 6: 인간화된
PNPLA3
rs738409-rs738408
마우스 모델에서 siRNA 분자에 의한 간 섬유증의 예방
Amylin Pharmaceuticals (Clapper 2013)에 의해 개발된 "AMLN" 식이는 ALIOS 식이의 변형된 버전이다. 사료에는 콜레스테롤이 10배 증가되고(2%), 추가 수크로스가 포함된다. "AMLN" 식이에 배치된 마우스는 20~30주 후에 경증 내지 중등도의 섬유증을 일으킨다(Clapper, Mells and Kristiansen papers). 이 연구를 위해, 8 내지 10주령의 C57BL/6NCrl 수컷 마우스(Charles River Laboratories Inc.)에 전술한 바와 같이 AAV-비어있는 벡터 또는 AAV- PNPLA3 rs738409-rs738408 을 주사하여 질환 발병을 가속화하였다. AAV 주사시, 마우스는 정상 차우식이로 계속하거나, 수확때까지, 식수와 함께 55% 프룩토스 및 45% 글루코스(각각 Sigma, F0127 및 G7021)로 구성된 Envigo 식이, TD.170748에 두었다.
AAV 주사 및 식이 개시 2주 후, 인산 완충 식염수로 희석된 동물 킬로그램 당 5.0 밀리그램으로 피하 주사를 통해 단일 용량의 siRNA D-2324(0.5 mM)로 마우스를 처리하거나(Thermo Fisher Scientific,14190-136), 비히클 대조군으로 처리하였다. 수확까지 2주마다 투여를 반복하였다. 수확 시점에, 체중을 수집한 후, 이소플루란 마취하에 심장 천자를 통한 혈청, 이어서 간 중량이 수집되었다. 중간엽은 10% 중성 완충 포르말린을 통해 고정된 후 파라핀 가공 및 임베딩(embedding)을 하였다. 나머지 간을 유전자 발현 분석을 위해 스냅 냉동시켰다.
스냅 냉동된 간 조직을 전술한 바와 같이 RNA 및 유전자 발현 분석을 위해 처리하였다. 결과는 마우스 Gapdh에 대해 표준화된 지시된 유전자의 원시 Ct 값 및 상대 mRNA 발현 둘 모두로서 제시된다(Invitrogen으로부터의 TaqManTM 분석: 인간 PNPLA3, hs00228747_m1; 마우스 Pnpla3, Mm00504420_m1; 마우스 Col1a1, Mm00801666_g1; 마우스 Col3a1, Mm01254471_g1; Col4a1, Mm01210125_m1; 마우스 Gapdh, 4352932E). Col1a1, Col3a1 및 Col4a1은 간 성상 세포 활성화 및 간 섬유증과 관련된 세포외 매트릭스 마커이다(Baiocchini 2016).
포르말린-고정된 조직은 제조사의 지시에 따라 헤모톡실린, 에오신 및 마손(Masson)의 트리크롬 염색(각각 Dako, CS70030-2, CS70130-2, AR17311-2)을 위해 처리되었다. 항-평활근 액틴 염색은 항원 회수없이 및 DAKO 오토테이너를 사용하여 수행하였다. 과산화된(Peroxidazed) 1 및 스나이퍼(각각 Biocare, PX968 및 BS966)를 사용하여 슬라이드를 처리하고, 모노클로날 항-액틴, 알파-평활근 항체(Sigma, F3777)로 염색한 다음, 토끼 항-FITC (Invitrogen, 711900), Envision-토끼 HRP 중합체 (Dako, K4003), DAB+ (Dako, K3468), 및 헤모톡실린으로 염색하였다. 지방증, 염증, 타원 세포/담관 과형성, 및 aSMA-양성 세포의 양에 대한 스코어링은 협회-인증된 병리학자에 의해 수행되었다.
제조업체의 지시에 따라 마우스 TIMP1(R&D Systems, MTM100) 및 마우스 시토케라틴 18-M30 (Cusabio, CSB-E14265m)에 대해 혈청을 분석하였다. TIMP1 외에도, 사이토카인 18-M30은 조기 섬유증을 포함한, NAFLD/NASH의 잠재적 바이오마커로 확인되었다(Neuman 2014 and Yang 2015). 도 5a-l. 조기 섬유증의 발병을 예방하는 PNPLA3rs738409-rs738408 - 특이적 siRNA 분자의 능력을 평가하기 위해, 마우스는 AAV8-비어있는 벡터 (EV), 또는 AAV8-PNPLA3 rs738409-rs738408 , 또는 비히클을 제공받았으며, 규칙적인 차우식으로 유지되거나, 또는 AMLN 식이로 전환되었다. AAV 주사 2주 후, 마우스를 추가 10주 동안 격주로 siRNA, D-2324, 또는 비히클로 처리하였다; 총 6회의 주사 라운드. 10주 시점에 마우스를 수확하였다. 결과는 평균 및 표준 오차, 차우-공급된 AAV + 비히클 없음 및 AMLN-공급된 AAV8-PNPLA3 rs738409-rs738408 + 비히클, 그룹 당 N=8; AMLN-공급된 AAV8-PNPLA3 rs738409-rs738408 + 비히클 및 AAV8-PNPLA3 rs738409-rs738408 + siRNA, 그룹 당 N=12로 나타낸다. 별표는 Dunnett의 다중 비교 테스트를 사용하는 일원 분산 분석(One-way ANOVA)에 의해 생성된 AAV8-PNPLA3 rs738409-rs738408 - 비히클-처리된 코호트에 대한 통계적 유의성을 나타낸다. (A) 수확시 간 중량 (그램) 대 체중 (그램)의 비. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, 유의미하지 않음, AAV- PNPLA3 rs738409-rs738408 + siRNA, ****<0.0001. (B) qPCR에 의한 간에서의 인간 PNPLA3 mRNA 발현 및 사일런싱의 확인. (왼쪽) 원시 Ct 값 및 (오른쪽) 마우스 Gapdh에 대해 정규화된 상대 폴드 mRNA 발현; PNPLA3 rs738409-rs738408 + 비히클 및 PNPLA3 rs738409-rs738408 + siRNA 그룹 비교. (C) qPCR에 의한 간에서의 마우스 Pnpla3 mRNA 발현의 분석은 내인성 Pnpla3이 AAV-매개된 과-발현 또는 siRNA 사일런싱에 의해 크게 변경되지 않음을 나타낸다. (왼쪽) 원시 Ct 값 및 (오른쪽) 마우스 Gapdh에 대해 정규화된 상대 폴드 mRNA 발현; 차우-공급된 무-AAV 그룹을 AMLN-공급된 PNPLA3 rs738409-rs738408 + 비히클 및 PNPLA3 rs738409-rs738408 + siRNA 그룹과 비교. (D) 혈청 Timp1은 혈청 1 밀리리터 당 피코그램으로 제시되었다. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, ****<0.0001, AAV- PNPLA3 rs738409-rs738408 + siRNA, ****<0.0001. (E) 혈청 CK18m30은 혈청 1 밀리리터 당 피코그램으로 제시되었다. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, ****<0.0001, AAV- PNPLA3 rs738409-rs738408 + siRNA, ****<0.0001. (F) H&E 염색에 기초한 염증의 조직학적 표시는 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, *=0.0108, AAV- PNPLA3 rs738409-rs738408 + siRNA, ****<0.0001. (G) H&E 염색에 기초한 타원형 세포/담관 과형성의 조직학적 표시는 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, 유의미하지 않음, AAV- PNPLA3 rs738409-rs738408 + siRNA, **=0.0081. (H) 항-평활근 액틴에 대한 면역조직화학적 염색은 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, *=0.0101, AAV- PNPLA3 rs738409-rs738408 + siRNA, ***=0.0002. (I) 섬유증에 대한 마손(Masson)의 트리크롬 염색은 다음과 같이 점수가 매겨진다: 정상 한계치 내 (0), 최소 (1), 미약 (2), 보통 (3), 및 중증 (4). 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, 유의미하지 않음, AAV- PNPLA3 rs738409-rs738408 + siRNA, 유의미하지 않음. (J) qPCR에 의한 간에서의 마우스 Col1a1 mRNA 발현. 마우스 Gapdh로 정규화된 상대 폴드 mRNA 발현. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, ****<0.0001, AAV- PNPLA3 rs738409-rs738408 + siRNA, ****<0.0001. (K) qPCR에 의한 간에서의 마우스 Col3a1 mRNA 발현. 마우스 Gapdh로 정규화된 상대 폴드 mRNA 발현. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, ****<0.0001, AAV- PNPLA3 rs738409-rs738408 + siRNA, ****<0.0001. (L) qPCR에 의한 간에서의 마우스 Col4a1 mRNA 발현. 마우스 Gapdh로 정규화된 상대 폴드 mRNA 발현. 조정된 P 값: AAV + 비히클 그룹 없음, ****<0.0001, AAV-EV + 비히클, ***<0.0005, AAV- PNPLA3 rs738409-rs738408 + siRNA, **<0.0041.
SEQUENCE LISTING
<110> RULIFSON, INGRID
MURRAY, JUSTIN K.
HOMANN, OLIVER
OLLMANN, MICHAEL
<120> RNAI CONSTRUCTS FOR INHIBITING PNPLA3 EXPRESSION
<130> IPA200643-US
<140>
<141>
<150> US 62/597,841
<151> 2017-12-12
<160> 2440
<170> PatentIn version 3.5
<210> 1
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1
gggcaauaaa guaccugcuu u 21
<210> 2
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2
agcagguacu uuauugcccu u 21
<210> 3
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 3
cggccaaugu ccaccagcuu u 21
<210> 4
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 4
agcuggugga cauuggccgu u 21
<210> 5
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 5
gguccagccu gaacuucuuu u 21
<210> 6
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 6
aagaaguuca ggcuggaccu u 21
<210> 7
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 7
gcuucauccc cuucuacagu u 21
<210> 8
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 8
cuguagaagg ggaugaagcu u 21
<210> 9
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 9
gcggcuuccu gggcuucuau u 21
<210> 10
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 10
uagaagccca ggaagccgcu u 21
<210> 11
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 11
gccucugagc ugaguugguu u 21
<210> 12
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 12
accaacucag cucagaggcu u 21
<210> 13
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 13
gugacaacgu acccuucauu u 21
<210> 14
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 14
augaagggua cguugucacu u 21
<210> 15
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 15
cccgccucca ggucccaaau u 21
<210> 16
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 16
uuugggaccu ggaggcgggu u 21
<210> 17
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 17
cuucaucccc uucuacaguu u 21
<210> 18
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 18
acuguagaag gggaugaagu u 21
<210> 19
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 19
gguauguucc ugcuucaugu u 21
<210> 20
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 20
caugaagcag gaacauaccu u 21
<210> 21
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 21
guauguuccu gcuucaugcu u 21
<210> 22
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 22
gcaugaagca ggaacauacu u 21
<210> 23
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 23
uauguuccug cuucaugccu u 21
<210> 24
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 24
ggcaugaagc aggaacauau u 21
<210> 25
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 25
auguuccugc uucaugcccu u 21
<210> 26
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 26
gggcaugaag caggaacauu u 21
<210> 27
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 27
uguuccugcu ucaugcccuu u 21
<210> 28
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 28
agggcaugaa gcaggaacau u 21
<210> 29
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 29
guuccugcuu caugcccuuu u 21
<210> 30
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 30
aagggcauga agcaggaacu u 21
<210> 31
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 31
uuccugcuuc augcccuucu u 21
<210> 32
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 32
gaagggcaug aagcaggaau u 21
<210> 33
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 33
uccugcuuca ugcccuucuu u 21
<210> 34
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 34
agaagggcau gaagcaggau u 21
<210> 35
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 35
ccugcuucau gcccuucuau u 21
<210> 36
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 36
uagaagggca ugaagcaggu u 21
<210> 37
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 37
cugcuucaug cccuucuacu u 21
<210> 38
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 38
guagaagggc augaagcagu u 21
<210> 39
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 39
ugcuucaugc ccuucuacau u 21
<210> 40
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 40
uguagaaggg caugaagcau u 21
<210> 41
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 41
gcuucaugcc cuucuacagu u 21
<210> 42
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 42
cuguagaagg gcaugaagcu u 21
<210> 43
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 43
cuucaugccc uucuacaguu u 21
<210> 44
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 44
acuguagaag ggcaugaagu u 21
<210> 45
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 45
uucaugcccu ucuacagugu u 21
<210> 46
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 46
cacuguagaa gggcaugaau u 21
<210> 47
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 47
ucaugcccuu cuacaguggu u 21
<210> 48
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 48
ccacuguaga agggcaugau u 21
<210> 49
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 49
caugcccuuc uacaguggcu u 21
<210> 50
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 50
gccacuguag aagggcaugu u 21
<210> 51
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 51
augcccuucu acaguggccu u 21
<210> 52
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 52
ggccacugua gaagggcauu u 21
<210> 53
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 53
ugcccuucua caguggccuu u 21
<210> 54
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 54
aggccacugu agaagggcau u 21
<210> 55
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 55
gcccuucuac aguggccuuu u 21
<210> 56
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 56
aaggccacug uagaagggcu u 21
<210> 57
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 57
gguauguucc ugcuucaucu u 21
<210> 58
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 58
gaugaagcag gaacauaccu u 21
<210> 59
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 59
guauguuccu gcuucauccu u 21
<210> 60
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 60
ggaugaagca ggaacauacu u 21
<210> 61
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 61
uauguuccug cuucaucccu u 21
<210> 62
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 62
gggaugaagc aggaacauau u 21
<210> 63
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 63
auguuccugc uucauccccu u 21
<210> 64
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 64
ggggaugaag caggaacauu u 21
<210> 65
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 65
uguuccugcu ucauccccuu u 21
<210> 66
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 66
aggggaugaa gcaggaacau u 21
<210> 67
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 67
guuccugcuu cauccccuuu u 21
<210> 68
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 68
aaggggauga agcaggaacu u 21
<210> 69
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 69
uuccugcuuc auccccuucu u 21
<210> 70
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 70
gaaggggaug aagcaggaau u 21
<210> 71
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 71
uccugcuuca uccccuucuu u 21
<210> 72
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 72
agaaggggau gaagcaggau u 21
<210> 73
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 73
ccugcuucau ccccuucuau u 21
<210> 74
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 74
uagaagggga ugaagcaggu u 21
<210> 75
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 75
cugcuucauc cccuucuacu u 21
<210> 76
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 76
guagaagggg augaagcagu u 21
<210> 77
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 77
ugcuucaucc ccuucuacau u 21
<210> 78
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 78
uguagaaggg gaugaagcau u 21
<210> 79
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 79
uucauccccu ucuacagugu u 21
<210> 80
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 80
cacuguagaa ggggaugaau u 21
<210> 81
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 81
ucauccccuu cuacaguggu u 21
<210> 82
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 82
ccacuguaga aggggaugau u 21
<210> 83
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 83
cauccccuuc uacaguggcu u 21
<210> 84
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 84
gccacuguag aaggggaugu u 21
<210> 85
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 85
uccccuucua caguggccuu u 21
<210> 86
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 86
aggccacugu agaaggggau u 21
<210> 87
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 87
gaucaggacc cgagccgauu u 21
<210> 88
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 88
aucggcucgg guccugaucu u 21
<210> 89
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 89
ugggcuucua ccacgucguu u 21
<210> 90
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 90
acgacguggu agaagcccau u 21
<210> 91
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 91
gagcgagcac gccccgcauu u 21
<210> 92
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 92
augcggggcg ugcucgcucu u 21
<210> 93
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 93
ugcacugcgu cggcguccuu u 21
<210> 94
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 94
aggacgccga cgcagugcau u 21
<210> 95
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 95
uggagcagac ucugcagguu u 21
<210> 96
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 96
accugcagag ucugcuccau u 21
<210> 97
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 97
ugcagguccu cucagaucuu u 21
<210> 98
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 98
agaucugaga ggaccugcau u 21
<210> 99
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 99
cccggccaau guccaccauu u 21
<210> 100
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 100
augguggaca uuggccgggu u 21
<210> 101
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 101
uucuacagug gccuuaucuu u 21
<210> 102
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 102
agauaaggcc acuguagaau u 21
<210> 103
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 103
ucuacagugg ccuuauccuu u 21
<210> 104
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 104
aggauaaggc cacuguagau u 21
<210> 105
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 105
cuuccuucag aggcgugcuu u 21
<210> 106
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 106
agcacgccuc ugaaggaagu u 21
<210> 107
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 107
uuccuucaga ggcgugcgau u 21
<210> 108
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 108
ucgcacgccu cugaaggaau u 21
<210> 109
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 109
gcgugcgaua uguggauguu u 21
<210> 110
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 110
acauccacau aucgcacgcu u 21
<210> 111
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 111
cgugcgauau guggauggau u 21
<210> 112
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 112
uccauccaca uaucgcacgu u 21
<210> 113
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 113
uggauggagg agugagugau u 21
<210> 114
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 114
ucacucacuc cuccauccau u 21
<210> 115
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 115
acguacccuu cauugauguu u 21
<210> 116
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 116
acaucaauga aggguacguu u 21
<210> 117
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 117
uggacaucac caagcucauu u 21
<210> 118
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 118
augagcuugg ugauguccau u 21
<210> 119
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 119
caccugcguc ucagcaucuu u 21
<210> 120
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 120
agaugcugag acgcaggugu u 21
<210> 121
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 121
accugcgucu cagcauccuu u 21
<210> 122
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 122
aggaugcuga gacgcagguu u 21
<210> 123
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 123
ccagagacug gugacauguu u 21
<210> 124
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 124
acaugucacc agucucuggu u 21
<210> 125
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 125
auggcuucca gauaugccuu u 21
<210> 126
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 126
aggcauaucu ggaagccauu u 21
<210> 127
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 127
ccgccuccag gucccaaauu u 21
<210> 128
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 128
auuugggacc uggaggcggu u 21
<210> 129
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 129
uaccugcugg ugcugagguu u 21
<210> 130
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 130
accucagcac cagcagguau u 21
<210> 131
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 131
accugcuggu gcugaggguu u 21
<210> 132
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 132
acccucagca ccagcagguu u 21
<210> 133
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 133
cucuccaccu uucccaguuu u 21
<210> 134
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 134
aacugggaaa gguggagagu u 21
<210> 135
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 135
uuuuucaccu aacuaaaauu u 21
<210> 136
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 136
auuuuaguua ggugaaaaau u 21
<210> 137
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 137
cggccaaugu ccaccagcuu u 21
<210> 138
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 138
agcuggugga cauuggccgu u 21
<210> 139
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 139
gguccagccu gaacuucuuu u 21
<210> 140
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 140
aagaaguuca ggcuggaccu u 21
<210> 141
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 141
gcggcuuccu gggcuucuau u 21
<210> 142
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 142
uagaagccca ggaagccgcu u 21
<210> 143
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 143
gugacaacgu acccuucauu u 21
<210> 144
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 144
augaagggua cguugucacu u 21
<210> 145
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 145
gguauguucc ugcuucaugu u 21
<210> 146
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 146
caugaagcag gaacauaccu u 21
<210> 147
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 147
guauguuccu gcuucaugcu u 21
<210> 148
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 148
gcaugaagca ggaacauacu u 21
<210> 149
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 149
uguuccugcu ucaugcccuu u 21
<210> 150
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 150
agggcaugaa gcaggaacau u 21
<210> 151
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 151
guuccugcuu caugcccuuu u 21
<210> 152
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 152
aagggcauga agcaggaacu u 21
<210> 153
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 153
ccugcuucau gcccuucuau u 21
<210> 154
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 154
uagaagggca ugaagcaggu u 21
<210> 155
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 155
gcuucaugcc cuucuacagu u 21
<210> 156
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 156
cuguagaagg gcaugaagcu u 21
<210> 157
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 157
cuucaugccc uucuacaguu u 21
<210> 158
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 158
acuguagaag ggcaugaagu u 21
<210> 159
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 159
uucaugcccu ucuacagugu u 21
<210> 160
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 160
cacuguagaa gggcaugaau u 21
<210> 161
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 161
auggcuucca gauaugccuu u 21
<210> 162
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 162
aggcauaucu ggaagccauu u 21
<210> 163
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 163
augcccuucu acaguggccu u 21
<210> 164
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 164
ggccacugua gaagggcauu u 21
<210> 165
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 165
gcuucaugcc cuucuacauu u 21
<210> 166
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 166
auguagaagg gcaugaagcu u 21
<210> 167
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 167
gggcaauaaa guaccugcuu u 21
<210> 168
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 168
agcagguacu uuauugcccu u 21
<210> 169
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 169
cggccaaugu ccaccagcuu u 21
<210> 170
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 170
agcuggugga cauuggccgu u 21
<210> 171
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 171
gguccagccu gaacuucuuu u 21
<210> 172
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 172
aagaaguuca ggcuggaccu u 21
<210> 173
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 173
gcuucauccc cuucuacagu u 21
<210> 174
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 174
cuguagaagg ggaugaagcu u 21
<210> 175
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 175
gcggcuuccu gggcuucuau u 21
<210> 176
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 176
uagaagccca ggaagccgcu u 21
<210> 177
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 177
gccucugagc ugaguugguu u 21
<210> 178
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 178
accaacucag cucagaggcu u 21
<210> 179
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 179
gugacaacgu acccuucauu u 21
<210> 180
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 180
augaagggua cguugucacu u 21
<210> 181
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 181
cccgccucca ggucccaaau u 21
<210> 182
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 182
uuugggaccu ggaggcgggu u 21
<210> 183
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 183
cuucaucccc uucuacaguu u 21
<210> 184
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 184
acuguagaag gggaugaagu u 21
<210> 185
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 185
gguauguucc ugcuucaugu u 21
<210> 186
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 186
caugaagcag gaacauaccu u 21
<210> 187
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 187
guauguuccu gcuucaugcu u 21
<210> 188
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 188
gcaugaagca ggaacauacu u 21
<210> 189
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 189
uauguuccug cuucaugccu u 21
<210> 190
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 190
ggcaugaagc aggaacauau u 21
<210> 191
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 191
auguuccugc uucaugcccu u 21
<210> 192
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 192
gggcaugaag caggaacauu u 21
<210> 193
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 193
uguuccugcu ucaugcccuu u 21
<210> 194
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 194
agggcaugaa gcaggaacau u 21
<210> 195
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 195
guuccugcuu caugcccuuu u 21
<210> 196
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 196
aagggcauga agcaggaacu u 21
<210> 197
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 197
uuccugcuuc augcccuucu u 21
<210> 198
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 198
gaagggcaug aagcaggaau u 21
<210> 199
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 199
uccugcuuca ugcccuucuu u 21
<210> 200
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 200
agaagggcau gaagcaggau u 21
<210> 201
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 201
ccugcuucau gcccuucuau u 21
<210> 202
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 202
uagaagggca ugaagcaggu u 21
<210> 203
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 203
cugcuucaug cccuucuacu u 21
<210> 204
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 204
guagaagggc augaagcagu u 21
<210> 205
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 205
ugcuucaugc ccuucuacau u 21
<210> 206
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 206
uguagaaggg caugaagcau u 21
<210> 207
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 207
gcuucaugcc cuucuacagu u 21
<210> 208
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 208
cuguagaagg gcaugaagcu u 21
<210> 209
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 209
cuucaugccc uucuacaguu u 21
<210> 210
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 210
acuguagaag ggcaugaagu u 21
<210> 211
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 211
uucaugcccu ucuacagugu u 21
<210> 212
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 212
cacuguagaa gggcaugaau u 21
<210> 213
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 213
ucaugcccuu cuacaguggu u 21
<210> 214
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 214
ccacuguaga agggcaugau u 21
<210> 215
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 215
caugcccuuc uacaguggcu u 21
<210> 216
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 216
gccacuguag aagggcaugu u 21
<210> 217
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 217
augcccuucu acaguggccu u 21
<210> 218
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 218
ggccacugua gaagggcauu u 21
<210> 219
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 219
ugcccuucua caguggccuu u 21
<210> 220
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 220
aggccacugu agaagggcau u 21
<210> 221
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 221
gcccuucuac aguggccuuu u 21
<210> 222
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 222
aaggccacug uagaagggcu u 21
<210> 223
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 223
gguauguucc ugcuucaucu u 21
<210> 224
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 224
gaugaagcag gaacauaccu u 21
<210> 225
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 225
guauguuccu gcuucauccu u 21
<210> 226
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 226
ggaugaagca ggaacauacu u 21
<210> 227
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 227
uauguuccug cuucaucccu u 21
<210> 228
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 228
gggaugaagc aggaacauau u 21
<210> 229
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 229
auguuccugc uucauccccu u 21
<210> 230
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 230
ggggaugaag caggaacauu u 21
<210> 231
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 231
uguuccugcu ucauccccuu u 21
<210> 232
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 232
aggggaugaa gcaggaacau u 21
<210> 233
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 233
guuccugcuu cauccccuuu u 21
<210> 234
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 234
aaggggauga agcaggaacu u 21
<210> 235
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 235
uuccugcuuc auccccuucu u 21
<210> 236
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 236
gaaggggaug aagcaggaau u 21
<210> 237
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 237
uccugcuuca uccccuucuu u 21
<210> 238
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 238
agaaggggau gaagcaggau u 21
<210> 239
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 239
ccugcuucau ccccuucuau u 21
<210> 240
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 240
uagaagggga ugaagcaggu u 21
<210> 241
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 241
cugcuucauc cccuucuacu u 21
<210> 242
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 242
guagaagggg augaagcagu u 21
<210> 243
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 243
ugcuucaucc ccuucuacau u 21
<210> 244
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 244
uguagaaggg gaugaagcau u 21
<210> 245
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 245
uucauccccu ucuacagugu u 21
<210> 246
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 246
cacuguagaa ggggaugaau u 21
<210> 247
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 247
ucauccccuu cuacaguggu u 21
<210> 248
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 248
ccacuguaga aggggaugau u 21
<210> 249
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 249
cauccccuuc uacaguggcu u 21
<210> 250
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 250
gccacuguag aaggggaugu u 21
<210> 251
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 251
uccccuucua caguggccuu u 21
<210> 252
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 252
aggccacugu agaaggggau u 21
<210> 253
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 253
gaucaggacc cgagccgauu u 21
<210> 254
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 254
aucggcucgg guccugaucu u 21
<210> 255
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 255
ugggcuucua ccacgucguu u 21
<210> 256
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 256
acgacguggu agaagcccau u 21
<210> 257
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 257
gagcgagcac gccccgcauu u 21
<210> 258
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 258
augcggggcg ugcucgcucu u 21
<210> 259
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 259
ugcacugcgu cggcguccuu u 21
<210> 260
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 260
aggacgccga cgcagugcau u 21
<210> 261
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 261
uggagcagac ucugcagguu u 21
<210> 262
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 262
accugcagag ucugcuccau u 21
<210> 263
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 263
ugcagguccu cucagaucuu u 21
<210> 264
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 264
agaucugaga ggaccugcau u 21
<210> 265
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 265
cccggccaau guccaccauu u 21
<210> 266
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 266
augguggaca uuggccgggu u 21
<210> 267
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 267
uucuacagug gccuuaucuu u 21
<210> 268
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 268
agauaaggcc acuguagaau u 21
<210> 269
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 269
ucuacagugg ccuuauccuu u 21
<210> 270
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 270
aggauaaggc cacuguagau u 21
<210> 271
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 271
cuuccuucag aggcgugcuu u 21
<210> 272
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 272
agcacgccuc ugaaggaagu u 21
<210> 273
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 273
uuccuucaga ggcgugcgau u 21
<210> 274
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 274
ucgcacgccu cugaaggaau u 21
<210> 275
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 275
gcgugcgaua uguggauguu u 21
<210> 276
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 276
acauccacau aucgcacgcu u 21
<210> 277
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 277
cgugcgauau guggauggau u 21
<210> 278
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 278
uccauccaca uaucgcacgu u 21
<210> 279
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 279
uggauggagg agugagugau u 21
<210> 280
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 280
ucacucacuc cuccauccau u 21
<210> 281
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 281
acguacccuu cauugauguu u 21
<210> 282
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 282
acaucaauga aggguacguu u 21
<210> 283
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 283
uggacaucac caagcucauu u 21
<210> 284
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 284
augagcuugg ugauguccau u 21
<210> 285
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 285
caccugcguc ucagcaucuu u 21
<210> 286
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 286
agaugcugag acgcaggugu u 21
<210> 287
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 287
accugcgucu cagcauccuu u 21
<210> 288
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 288
aggaugcuga gacgcagguu u 21
<210> 289
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 289
ccagagacug gugacauguu u 21
<210> 290
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 290
acaugucacc agucucuggu u 21
<210> 291
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 291
auggcuucca gauaugccuu u 21
<210> 292
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 292
aggcauaucu ggaagccauu u 21
<210> 293
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 293
ccgccuccag gucccaaauu u 21
<210> 294
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 294
auuugggacc uggaggcggu u 21
<210> 295
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 295
uaccugcugg ugcugagguu u 21
<210> 296
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 296
accucagcac cagcagguau u 21
<210> 297
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 297
accugcuggu gcugaggguu u 21
<210> 298
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 298
acccucagca ccagcagguu u 21
<210> 299
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 299
cucuccaccu uucccaguuu u 21
<210> 300
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 300
aacugggaaa gguggagagu u 21
<210> 301
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 301
uuuuucaccu aacuaaaauu u 21
<210> 302
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 302
auuuuaguua ggugaaaaau u 21
<210> 303
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 303
cggccaaugu ccaccagcuu u 21
<210> 304
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 304
agcuggugga cauuggccgu u 21
<210> 305
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 305
gguccagccu gaacuucuuu u 21
<210> 306
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 306
aagaaguuca ggcuggaccu u 21
<210> 307
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 307
gcggcuuccu gggcuucuau u 21
<210> 308
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 308
uagaagccca ggaagccgcu u 21
<210> 309
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 309
gugacaacgu acccuucauu u 21
<210> 310
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 310
augaagggua cguugucacu u 21
<210> 311
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 311
gguauguucc ugcuucaugu u 21
<210> 312
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 312
caugaagcag gaacauaccu u 21
<210> 313
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 313
guauguuccu gcuucaugcu u 21
<210> 314
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 314
gcaugaagca ggaacauacu u 21
<210> 315
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 315
uguuccugcu ucaugcccuu u 21
<210> 316
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 316
agggcaugaa gcaggaacau u 21
<210> 317
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 317
guuccugcuu caugcccuuu u 21
<210> 318
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 318
aagggcauga agcaggaacu u 21
<210> 319
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 319
ccugcuucau gcccuucuau u 21
<210> 320
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 320
uagaagggca ugaagcaggu u 21
<210> 321
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 321
gcuucaugcc cuucuacagu u 21
<210> 322
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 322
cuguagaagg gcaugaagcu u 21
<210> 323
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 323
cuucaugccc uucuacaguu u 21
<210> 324
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 324
acuguagaag ggcaugaagu u 21
<210> 325
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 325
uucaugcccu ucuacagugu u 21
<210> 326
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 326
cacuguagaa gggcaugaau u 21
<210> 327
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 327
auggcuucca gauaugccuu u 21
<210> 328
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 328
aggcauaucu ggaagccauu u 21
<210> 329
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 329
augcccuucu acaguggccu u 21
<210> 330
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 330
ggccacugua gaagggcauu u 21
<210> 331
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 331
gcuucaugcc cuucuacauu u 21
<210> 332
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 332
auguagaagg gcaugaagcu u 21
<210> 333
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 333
ggaaagacug uuccaaaaau u 21
<210> 334
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 334
uuuuuggaac agucuuuccu u 21
<210> 335
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 335
gguauguucc ugcuucaugu u 21
<210> 336
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 336
caugaagcag gaacauaccu u 21
<210> 337
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 337
guauguuccu gcuucaugcu u 21
<210> 338
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 338
gcaugaagca ggaacauacu u 21
<210> 339
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 339
uguuccugcu ucaugcccuu u 21
<210> 340
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 340
agggcaugaa gcaggaacau u 21
<210> 341
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 341
gcuucaugcc cuucuacagu u 21
<210> 342
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 342
cuguagaagg gcaugaagcu u 21
<210> 343
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 343
cuucaugccc uucuacaguu u 21
<210> 344
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 344
acuguagaag ggcaugaagu u 21
<210> 345
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 345
gcggcuuccu gggcuucuau u 21
<210> 346
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 346
uagaagccca ggaagccgcu u 21
<210> 347
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 347
guuccugcuu caugcccuuu u 21
<210> 348
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 348
aagggcauga agcaggaacu u 21
<210> 349
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 349
auggcuucca gauaugccuu u 21
<210> 350
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 350
aggcauaucu ggaagccauu u 21
<210> 351
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 351
ccugcuucau gcccuucuau u 21
<210> 352
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 352
uagaagggca ugaagcaggu u 21
<210> 353
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 353
uucaugcccu ucuacaguuu u 21
<210> 354
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 354
aacuguagaa gggcaugaau u 21
<210> 355
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 355
uucaugcccu ucuacagugu u 21
<210> 356
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 356
cacuguagaa gggcaugaau u 21
<210> 357
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 357
gcuucaugcc cuucuacauu u 21
<210> 358
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 358
auguagaagg gcaugaagcu u 21
<210> 359
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 359
gguccagccu gaacuucuuu u 21
<210> 360
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 360
aagaaguuca ggcuggaccu u 21
<210> 361
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 361
gcggcuuccu gggcuucuau u 21
<210> 362
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 362
uagaagccca ggaagccgcu u 21
<210> 363
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 363
gcggcuuccu gggcuucuau u 21
<210> 364
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 364
uagaagccca ggaagccgcu u 21
<210> 365
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 365
guuccugcuu caugcccuuu u 21
<210> 366
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 366
aagggcauga agcaggaacu u 21
<210> 367
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 367
guuccugcuu caugcccuuu u 21
<210> 368
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 368
aagggcauga agcaggaacu u 21
<210> 369
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 369
ccugcuucau gcccuucuau u 21
<210> 370
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 370
uagaagggca ugaagcaggu u 21
<210> 371
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 371
ccugcuucau gcccuucuau u 21
<210> 372
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 372
uagaagggca ugaagcaggu u 21
<210> 373
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 373
augcccuucu acaguggccu u 21
<210> 374
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 374
ggccacugua gaagggcauu u 21
<210> 375
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 375
auggcuucca gauaugccuu u 21
<210> 376
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 376
aggcauaucu ggaagccauu u 21
<210> 377
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 377
gugacaacgu acccuucauu u 21
<210> 378
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 378
augaagggua cguugucacu u 21
<210> 379
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 379
guauguuccu gcuucaugcu u 21
<210> 380
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 380
gcaugaagca ggaacauacu u 21
<210> 381
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 381
guauguuccu gcuucaugcu u 21
<210> 382
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 382
gcaugaagca ggaacauacu u 21
<210> 383
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 383
guauguuccu gcuucaugcu u 21
<210> 384
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 384
gcaugaagca ggaacauacu u 21
<210> 385
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 385
guauguuccu gcuucaugcc u 21
<210> 386
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 386
aggcaugaag caggaacaua cuu 23
<210> 387
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 387
ugguauguuc cugcuucaug u 21
<210> 388
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 388
gcaugaagca ggaacauacc auu 23
<210> 389
<211> 19
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 389
guauguuccu gcuucaugu 19
<210> 390
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 390
gcaugaagca ggaacauacu u 21
<210> 391
<211> 20
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (20)..(20)
<223> Inverted abasic nucleotide
<400> 391
guauguuccu gcuucaugcn 20
<210> 392
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 392
gcaugaagca ggaacauacu u 21
<210> 393
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 393
gcuucaugcc cuucuacauu u 21
<210> 394
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 394
auguagaagg gcaugaagcu u 21
<210> 395
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 395
gcuucaugcc cuucuacauu u 21
<210> 396
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 396
auguagaagg gcaugaagcu u 21
<210> 397
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 397
gcuucaugcc cuucuacauu u 21
<210> 398
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 398
auguagaagg gcaugaagcu u 21
<210> 399
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 399
gcuucaugcc cuucuacauu u 21
<210> 400
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 400
auguagaagg gcaugaagcu u 21
<210> 401
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 401
gcuucaugcc cuucuacauu u 21
<210> 402
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 402
auguagaagg gcaugaagcu u 21
<210> 403
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 403
gcuucaugcc cuucuacauu u 21
<210> 404
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 404
auguagaagg gcaugaagcu u 21
<210> 405
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 405
gcuucaugcc cuucuacauu u 21
<210> 406
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 406
auguagaagg gcaugaagcu u 21
<210> 407
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 407
gcuucaugcc cuucuacauu u 21
<210> 408
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 408
auguagaagg gcaugaagcu u 21
<210> 409
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 409
gcuucaugcc cuucuacauu u 21
<210> 410
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 410
auguagaagg gcaugaagcu u 21
<210> 411
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 411
gcuucaugcc cuucuacauu u 21
<210> 412
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 412
auguagaagg gcaugaagcu u 21
<210> 413
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 413
gcuucaugcc cuucuacauu u 21
<210> 414
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 414
auguagaagg gcaugaagcu u 21
<210> 415
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 415
gcuucaugcc cuucuacauu u 21
<210> 416
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 416
auguagaagg gcaugaagcu u 21
<210> 417
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 417
gcuucaugcc cuucuacauu u 21
<210> 418
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 418
auguagaagg gcaugaagcu u 21
<210> 419
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 419
gcuucaugcc cuucuacauu u 21
<210> 420
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 420
auguagaagg gcaugaagcu u 21
<210> 421
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 421
gcuucaugcc cuucuacauu u 21
<210> 422
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 422
auguagaagg gcaugaagcu u 21
<210> 423
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 423
gcuucaugcc cuucuacauu u 21
<210> 424
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 424
auguagaagg gcaugaagcu u 21
<210> 425
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 425
gcuucaugcc cuucuacauu u 21
<210> 426
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 426
auguagaagg gcaugaagcu u 21
<210> 427
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 427
gcuucaugcc cuucuacauu u 21
<210> 428
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 428
auguagaagg gcaugaagcu u 21
<210> 429
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 429
gcuucaugcc cuucuacauu u 21
<210> 430
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 430
auguagaagg gcaugaagcu u 21
<210> 431
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 431
gcuucaugcc cuucuacauu u 21
<210> 432
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 432
auguagaagg gcaugaagcu u 21
<210> 433
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 433
gcuucaugcc cuucuacauu u 21
<210> 434
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 434
auguagaagg gcaugaagcu u 21
<210> 435
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 435
gcuucaugcc cuucuacauu u 21
<210> 436
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 436
auguagaagg gcaugaagcu u 21
<210> 437
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 437
gcuucaugcc cuucuacauu u 21
<210> 438
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 438
auguagaagg gcaugaagcu u 21
<210> 439
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 439
gcuucaugcc cuucuacauu u 21
<210> 440
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 440
auguagaagg gcaugaagcu u 21
<210> 441
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 441
gcuucaugcc cuucuacagu u 21
<210> 442
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 442
aacuguagaa gggcaugaag cuu 23
<210> 443
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 443
cugcuucaug cccuucuaca u 21
<210> 444
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 444
auguagaagg gcaugaagca guu 23
<210> 445
<211> 19
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 445
gcuucaugcc cuucuacau 19
<210> 446
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 446
auguagaagg gcaugaagcu u 21
<210> 447
<211> 20
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (20)..(20)
<223> Inverted abasic nucleotide
<400> 447
gcuucaugcc cuucuacaun 20
<210> 448
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 448
auguagaagg gcaugaagcu u 21
<210> 449
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 449
gcuucaugcc cuucuacauu un 22
<210> 450
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 450
auguagaagg gcaugaagcu u 21
<210> 451
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 451
gcuucaugcc cuucuacauu u 21
<210> 452
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 452
auguagaagg gcaugaagcu u 21
<210> 453
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 453
gcuucaugcc cuucuacauu u 21
<210> 454
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 454
auguagaagg gcaugaagcu u 21
<210> 455
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 455
gcuucaugcc cuucuacauu u 21
<210> 456
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 456
auguagaagg gcaugaagcu u 21
<210> 457
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 457
gcuucaugcc cuucuacauu u 21
<210> 458
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 458
auguagaagg gcaugaagcu u 21
<210> 459
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 459
gcuucaugcc cuucuacauu u 21
<210> 460
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 460
auguagaagg gcaugaagcu u 21
<210> 461
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 461
gcuucaugcc cuucuacauu u 21
<210> 462
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 462
auguagaagg gcaugaagcu u 21
<210> 463
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 463
gcuucaugcc cuucuacauu u 21
<210> 464
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 464
auguagaagg gcaugaagcu u 21
<210> 465
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 465
gcuucaugcc cuucuacauu u 21
<210> 466
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 466
auguagaagg gcaugaagcu u 21
<210> 467
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 467
gcuucaugcc cuucuacauu u 21
<210> 468
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 468
auguagaagg gcaugaagcu u 21
<210> 469
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 469
guauguuccu gcuucaugcu un 22
<210> 470
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 470
gcaugaagca ggaacauacu u 21
<210> 471
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 471
gguauguucc ugcuucauuu u 21
<210> 472
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 472
aaugaagcag gaacauaccu u 21
<210> 473
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 473
guauguuccu gcuucauguu u 21
<210> 474
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 474
acaugaagca ggaacauacu u 21
<210> 475
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 475
cggccaaugu ccaccagcuu u 21
<210> 476
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 476
agcuggugga cauuggccgu u 21
<210> 477
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 477
uggagcagac ucugcagguu u 21
<210> 478
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 478
accugcagag ucugcuccau u 21
<210> 479
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 479
acguacccuu cauugauguu u 21
<210> 480
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 480
acaucaauga aggguacguu u 21
<210> 481
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 481
ccagagacug gugacauguu u 21
<210> 482
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 482
acaugucacc agucucuggu u 21
<210> 483
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 483
ngcuucaugc cuuucuacau uu 22
<210> 484
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 484
auguagaaag gcaugaagcu u 21
<210> 485
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 485
ngcuucaugc cuuucuacau uu 22
<210> 486
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 486
aaauguagaa aggcaugaag cuu 23
<210> 487
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 487
ngcuucaugc cuuucuacau uu 22
<210> 488
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 488
aaauguagaa aggcaugaag cuu 23
<210> 489
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 489
ugcuucaugc cuuucuacau u 21
<210> 490
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 490
uguagaaagg caugaagcau u 21
<210> 491
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 491
uauguuccug cuucaugcuu u 21
<210> 492
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 492
agcaugaagc aggaacauau u 21
<210> 493
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 493
uuccugcuuc augccuuuuu u 21
<210> 494
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 494
aaaaggcaug aagcaggaau u 21
<210> 495
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 495
ucaugccuuu cuacaguguu u 21
<210> 496
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 496
acacuguaga aaggcaugau u 21
<210> 497
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 497
caugccuuuc uacagugguu u 21
<210> 498
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 498
accacuguag aaaggcaugu u 21
<210> 499
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 499
augccuuucu acaguggcuu u 21
<210> 500
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 500
agccacugua gaaaggcauu u 21
<210> 501
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 501
gguauguucc ugcuucauau u 21
<210> 502
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 502
uaugaagcag gaacauaccu u 21
<210> 503
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 503
guauguuccu gcuucaugau u 21
<210> 504
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 504
ucaugaagca ggaacauacu u 21
<210> 505
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 505
uauguuccug cuucaugcau u 21
<210> 506
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 506
ugcaugaagc aggaacauau u 21
<210> 507
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 507
uuccugcuuc augccuuuau u 21
<210> 508
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 508
uaaaggcaug aagcaggaau u 21
<210> 509
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 509
cugcuucaug ccuuucuaau u 21
<210> 510
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 510
uuagaaaggc augaagcagu u 21
<210> 511
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 511
gcuucaugcc uuucuacaau u 21
<210> 512
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 512
uuguagaaag gcaugaagcu u 21
<210> 513
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 513
uucaugccuu ucuacaguau u 21
<210> 514
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 514
uacuguagaa aggcaugaau u 21
<210> 515
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 515
ucaugccuuu cuacagugau u 21
<210> 516
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 516
ucacuguaga aaggcaugau u 21
<210> 517
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 517
caugccuuuc uacaguggau u 21
<210> 518
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 518
uccacuguag aaaggcaugu u 21
<210> 519
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 519
augccuuucu acaguggcau u 21
<210> 520
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 520
ugccacugua gaaaggcauu u 21
<210> 521
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 521
acguacccuu cauugaugau u 21
<210> 522
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 522
ucaucaauga aggguacguu u 21
<210> 523
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 523
ccagagacug gugacaugau u 21
<210> 524
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 524
ucaugucacc agucucuggu u 21
<210> 525
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 525
auggcuucca gauaugccau u 21
<210> 526
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 526
uggcauaucu ggaagccauu u 21
<210> 527
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 527
guuccugcuu caugccuuuu u 21
<210> 528
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 528
aaaggcauga agcaggaacu u 21
<210> 529
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 529
ccugcuucau gccuuucuau u 21
<210> 530
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 530
uagaaaggca ugaagcaggu u 21
<210> 531
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 531
gcuucaugcc uuucuacauu u 21
<210> 532
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 532
auguagaaag gcaugaagcu u 21
<210> 533
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 533
cuucaugccu uucuacaguu u 21
<210> 534
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 534
acuguagaaa ggcaugaagu u 21
<210> 535
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 535
uucaugccuu ucuacaguuu u 21
<210> 536
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 536
aacuguagaa aggcaugaau u 21
<210> 537
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 537
gcuucauccc uuucuacauu u 21
<210> 538
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 538
auguagaaag ggaugaagcu u 21
<210> 539
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 539
ngcuucaugc ccuucuacau uu 22
<210> 540
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 540
auguagaagg gcaugaagcu u 21
<210> 541
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 541
ngcuucaugc ccuucuacau uu 22
<210> 542
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 542
aaauguagaa gggcaugaag cuu 23
<210> 543
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 543
ngcuucaugc ccuucuacau uu 22
<210> 544
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 544
aaauguagaa gggcaugaag cuu 23
<210> 545
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 545
ngcggcuucc ugggcuucua uu 22
<210> 546
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 546
uagaagccca ggaagccgcu u 21
<210> 547
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 547
ncugcggcuu ccugggcuuc ua 22
<210> 548
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 548
uagaagccca ggaagccgca guu 23
<210> 549
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 549
cugcggcuuc cugggcuucu n 21
<210> 550
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 550
uagaagccca ggaagccgca guu 23
<210> 551
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 551
ncugcggcuu ccugggcuuc ua 22
<210> 552
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 552
uagaagccca ggaagccgca guu 23
<210> 553
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 553
ngcggcuucc ugggcuucua uu 22
<210> 554
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 554
uagaagccca ggaagccgcu u 21
<210> 555
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 555
cugcggcuuc cugggcuucu n 21
<210> 556
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 556
uagaagccca ggaagccgca guu 23
<210> 557
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 557
ncugcggcuu ccugggcuuc ua 22
<210> 558
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 558
uagaagccca ggaagccgca guu 23
<210> 559
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 559
ngcggcuucc ugggcuucua uu 22
<210> 560
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 560
uagaagccca ggaagccgcu u 21
<210> 561
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 561
cugcggcuuc cugggcuucu n 21
<210> 562
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 562
uagaagccca ggaagccgca guu 23
<210> 563
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 563
ncugcggcuu ccugggcuuc ua 22
<210> 564
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 564
uagaagccca ggaagccgca guu 23
<210> 565
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 565
ngcggcuucc ugggcuucua uu 22
<210> 566
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 566
uagaagccca ggaagccgcu u 21
<210> 567
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 567
ncugcggcuu ccugggcuuc ua 22
<210> 568
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 568
uagaagccca ggaagccgca guu 23
<210> 569
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 569
ncugcggcuu ccugggcuuc ua 22
<210> 570
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 570
uagaagccca ggaagccgca guu 23
<210> 571
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 571
ncugcggcuu ccugggcuuc ua 22
<210> 572
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 572
uagaagccca ggaagccgca guu 23
<210> 573
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 573
nauggcuucc agauaugccu uu 22
<210> 574
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 574
aggcauaucu ggaagccauu u 21
<210> 575
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 575
nacauggcuu ccagauaugc cu 22
<210> 576
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 576
aggcauaucu ggaagccaug uuu 23
<210> 577
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 577
acauggcuuc cagauaugcc n 21
<210> 578
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 578
aggcauaucu ggaagccaug uuu 23
<210> 579
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 579
nacauggcuu ccagauaugc cu 22
<210> 580
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 580
aggcauaucu ggaagccaug uuu 23
<210> 581
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 581
nauggcuucc agauaugccu uu 22
<210> 582
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 582
aggcauaucu ggaagccauu u 21
<210> 583
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 583
acauggcuuc cagauaugcc n 21
<210> 584
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 584
aggcauaucu ggaagccaug uuu 23
<210> 585
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 585
nacauggcuu ccagauaugc cu 22
<210> 586
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 586
aggcauaucu ggaagccaug uuu 23
<210> 587
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 587
nauggcuucc agauaugccu uu 22
<210> 588
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 588
aggcauaucu ggaagccauu u 21
<210> 589
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 589
acauggcuuc cagauaugcc n 21
<210> 590
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 590
aggcauaucu ggaagccaug uuu 23
<210> 591
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 591
nacauggcuu ccagauaugc cu 22
<210> 592
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 592
aggcauaucu ggaagccaug uuu 23
<210> 593
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 593
nauggcuucc agauaugccu uu 22
<210> 594
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 594
aggcauaucu ggaagccauu u 21
<210> 595
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 595
acauggcuuc cagauaugcc n 21
<210> 596
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 596
aggcauaucu ggaagccaug uuu 23
<210> 597
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 597
nacauggcuu ccagauaugc cu 22
<210> 598
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 598
aggcauaucu ggaagccaug uuu 23
<210> 599
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 599
nacauggcuu ccagauaugc cu 22
<210> 600
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 600
aggcauaucu ggaagccaug uuu 23
<210> 601
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 601
nacauggcuu ccagauaugc cu 22
<210> 602
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 602
aggcauaucu ggaagccaug uuu 23
<210> 603
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 603
nacauggcuu ccagauaugc cu 22
<210> 604
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 604
aggcauaucu ggaagccaug uuu 23
<210> 605
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 605
nacguacccu ucauugaugu uu 22
<210> 606
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 606
acaucaauga aggguacguu u 21
<210> 607
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 607
ncaacguacc cuucauugau gu 22
<210> 608
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 608
acaucaauga aggguacguu guu 23
<210> 609
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 609
ncaacguacc cuucauugau gu 22
<210> 610
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 610
acaucaauga aggguacguu guu 23
<210> 611
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 611
nacguacccu ucauugaugu uu 22
<210> 612
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 612
acaucaauga aggguacguu u 21
<210> 613
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 613
caacguaccc uucauugaug n 21
<210> 614
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 614
acaucaauga aggguacguu guu 23
<210> 615
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 615
nacguacccu ucauugaugu uu 22
<210> 616
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 616
acaucaauga aggguacguu u 21
<210> 617
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 617
caacguaccc uucauugaug n 21
<210> 618
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 618
acaucaauga aggguacguu guu 23
<210> 619
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 619
ncaacguacc cuucauugau gu 22
<210> 620
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 620
acaucaauga aggguacguu guu 23
<210> 621
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 621
nacguacccu ucauugaugu uu 22
<210> 622
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 622
acaucaauga aggguacguu u 21
<210> 623
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 623
caacguaccc uucauugaug n 21
<210> 624
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 624
acaucaauga aggguacguu guu 23
<210> 625
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 625
ncaacguacc cuucauugau gu 22
<210> 626
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 626
acaucaauga aggguacguu guu 23
<210> 627
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 627
ncaacguacc cuucauugau gu 22
<210> 628
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 628
acaucaauga aggguacguu guu 23
<210> 629
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 629
ncaacguacc cuucauugau gu 22
<210> 630
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 630
acaucaauga aggguacguu guu 23
<210> 631
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 631
ncaacguacc cuucauugau gu 22
<210> 632
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 632
acaucaauga aggguacguu guu 23
<210> 633
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 633
cugcuucaug ccuuucuaca u 21
<210> 634
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 634
auguagaaag gcaugaagca guu 23
<210> 635
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 635
cugcuucaug ccuuucuaca u 21
<210> 636
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 636
auguagaaag gcaugaagca guu 23
<210> 637
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 637
ngcuucaugc cuuucuacau uu 22
<210> 638
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 638
auguagaaag gcaugaagcu u 21
<210> 639
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 639
ngcuucaugc cuuucuacau uu 22
<210> 640
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 640
auguagaaag gcaugaagcu u 21
<210> 641
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 641
cugcuucaug ccuuucuaca u 21
<210> 642
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 642
auguagaaag gcaugaagca guu 23
<210> 643
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 643
cugcuucaug ccuuucuaca u 21
<210> 644
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 644
auguagaaag gcaugaagca guu 23
<210> 645
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 645
ncugcuucau gccuuucuac au 22
<210> 646
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 646
auguagaaag gcaugaagca guu 23
<210> 647
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 647
cugcuucaug ccuuucuaca n 21
<210> 648
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 648
auguagaaag gcaugaagca guu 23
<210> 649
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 649
ncugcuucau gccuuucuac au 22
<210> 650
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 650
auguagaaag gcaugaagca guu 23
<210> 651
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 651
ncugcuucau gccuuucuac au 22
<210> 652
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 652
auguagaaag gcaugaagca guu 23
<210> 653
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 653
cugcuucaug ccuuucuaca u 21
<210> 654
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 654
auguagaaag gcaugaagca guu 23
<210> 655
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 655
ncugcuucau gccuuucuac au 22
<210> 656
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 656
auguagaaag gcaugaagca guu 23
<210> 657
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 657
cugcuucaug ccuuucuaca u 21
<210> 658
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 658
auguagaaag gcaugaagca guu 23
<210> 659
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 659
cugcuucaug ccuuucuaca n 21
<210> 660
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 660
auguagaaag gcaugaagca guu 23
<210> 661
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 661
ncugcuucau gccuuucuac au 22
<210> 662
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 662
auguagaaag gcaugaagca guu 23
<210> 663
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 663
cugcuucaug ccuuucuaca u 21
<210> 664
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 664
auguagaaag gcaugaagca guu 23
<210> 665
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 665
cugcuucaug ccuuucuaca n 21
<210> 666
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 666
auguagaaag gcaugaagca guu 23
<210> 667
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 667
ncugcuucau gccuuucuac au 22
<210> 668
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 668
auguagaaag gcaugaagca guu 23
<210> 669
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 669
cugcuucaug ccuuucuaca n 21
<210> 670
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 670
auguagaaag gcaugaagca guu 23
<210> 671
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 671
ncugcuucau gccuuucuac au 22
<210> 672
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 672
auguagaaag gcaugaagca guu 23
<210> 673
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 673
ngcuucaugc cuuucuacau uu 22
<210> 674
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 674
auguagaaag gcaugaagcu u 21
<210> 675
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 675
ngcuucaugc cuuucuacau uu 22
<210> 676
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 676
auguagaaag gcaugaagcu u 21
<210> 677
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 677
ngcuucaugc cuuucuacau uu 22
<210> 678
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 678
auguagaaag gcaugaagcu u 21
<210> 679
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 679
ngcuucaugc cuuucuacau uu 22
<210> 680
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 680
auguagaaag gcaugaagcu u 21
<210> 681
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 681
ngcuucaugc cuuucuacau uu 22
<210> 682
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 682
auguagaaag gcaugaagcu u 21
<210> 683
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 683
cugcuucaug cccuucuaca u 21
<210> 684
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 684
auguagaagg gcaugaagca guu 23
<210> 685
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 685
ngcuucaugc ccuucuacau uu 22
<210> 686
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 686
auguagaagg gcaugaagcu u 21
<210> 687
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 687
ngcuucaugc ccuucuacau uu 22
<210> 688
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 688
auguagaagg gcaugaagcu u 21
<210> 689
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 689
ngcuucaugc ccuucuacau uu 22
<210> 690
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 690
auguagaagg gcaugaagcu u 21
<210> 691
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 691
cugcuucaug cccuucuaca n 21
<210> 692
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 692
auguagaagg gcaugaagca guu 23
<210> 693
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 693
ncugcuucau gcccuucuac au 22
<210> 694
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 694
auguagaagg gcaugaagca guu 23
<210> 695
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 695
ngcuucaugc ccuucuacau uu 22
<210> 696
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 696
auguagaagg gcaugaagcu u 21
<210> 697
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 697
auguuccugc uucaugccuu u 21
<210> 698
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 698
aggcaugaag caggaacauu u 21
<210> 699
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 699
uguuccugcu ucaugccuuu u 21
<210> 700
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 700
aaggcaugaa gcaggaacau u 21
<210> 701
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 701
ugccuuucua caguggccuu u 21
<210> 702
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 702
aggccacugu agaaaggcau u 21
<210> 703
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 703
cguacuucgu ccuuguaugu u 21
<210> 704
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 704
cauacaagga cgaaguacgu u 21
<210> 705
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 705
ngcuucaugc ccuucuacau uu 22
<210> 706
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 706
auguagaagg gcaugaagcu u 21
<210> 707
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 707
ngcuucaugc ccuucuacau uu 22
<210> 708
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 708
auguagaagg gcaugaagcu u 21
<210> 709
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 709
ngcuucaugc ccuucuacau uu 22
<210> 710
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 710
auguagaagg gcaugaagcu u 21
<210> 711
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 711
ngcuucaugc ccuucuacau uu 22
<210> 712
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 712
auguagaagg gcaugaagcu u 21
<210> 713
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 713
ngcuucaugc ccuucuacau uu 22
<210> 714
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 714
auguagaagg gcaugaagcu u 21
<210> 715
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 715
ngcuucaugc ccuucuacau uu 22
<210> 716
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 716
auguagaagg gcaugaagcu u 21
<210> 717
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 717
nccugcuuca ugccuuucua uu 22
<210> 718
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 718
uagaaaggca ugaagcaggu u 21
<210> 719
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 719
nccugcuuca ugccuuucua uu 22
<210> 720
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 720
uagaaaggca ugaagcaggu u 21
<210> 721
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 721
uuccugcuuc augccuuucu n 21
<210> 722
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 722
uagaaaggca ugaagcagga auu 23
<210> 723
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 723
nccugcuuca ugccuuucua uu 22
<210> 724
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 724
uagaaaggca ugaagcaggu u 21
<210> 725
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 725
uuccugcuuc augccuuucu n 21
<210> 726
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 726
uagaaaggca ugaagcagga auu 23
<210> 727
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 727
naugccuuuc uacaguggcu uu 22
<210> 728
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 728
agccacugua gaaaggcauu u 21
<210> 729
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 729
naugccuuuc uacaguggcu uu 22
<210> 730
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 730
agccacugua gaaaggcauu u 21
<210> 731
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 731
naugccuuuc uacaguggcu uu 22
<210> 732
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 732
agccacugua gaaaggcauu u 21
<210> 733
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 733
ucaugccuuu cuacaguggc n 21
<210> 734
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 734
agccacugua gaaaggcaug auu 23
<210> 735
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 735
naugccuuuc uacaguggcu uu 22
<210> 736
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 736
agccacugua gaaaggcauu u 21
<210> 737
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 737
nucaugccuu ucuacagugg cu 22
<210> 738
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 738
agccacugua gaaaggcaug auu 23
<210> 739
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 739
nugcuucaug ccuuucuaca gu 22
<210> 740
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 740
acuguagaaa ggcaugaagc auu 23
<210> 741
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 741
ncuucaugcc uuucuacagu uu 22
<210> 742
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 742
acuguagaaa ggcaugaagu u 21
<210> 743
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 743
ugcuucaugc cuuucuacag n 21
<210> 744
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 744
acuguagaaa ggcaugaagc auu 23
<210> 745
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 745
ncuucaugcc uuucuacagu uu 22
<210> 746
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 746
acuguagaaa ggcaugaagu u 21
<210> 747
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 747
ugcuucaugc cuuucuacag n 21
<210> 748
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 748
acuguagaaa ggcaugaagc auu 23
<210> 749
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 749
nugcuucaug ccuuucuaca gu 22
<210> 750
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 750
acuguagaaa ggcaugaagc auu 23
<210> 751
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 751
nugcuucaug ccuuucuaca gu 22
<210> 752
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 752
acuguagaaa ggcaugaagc auu 23
<210> 753
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 753
nugcuucaug ccuuucuaca gu 22
<210> 754
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 754
acuguagaaa ggcaugaagc auu 23
<210> 755
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 755
nugcuucaug ccuuucuaca gu 22
<210> 756
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 756
acuguagaaa ggcaugaagc auu 23
<210> 757
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 757
nguuccugcu ucaugccuuu uu 22
<210> 758
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 758
aaaggcauga agcaggaacu u 21
<210> 759
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 759
nccugcuuca ugccuuucua uu 22
<210> 760
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 760
uagaaaggca ugaagcaggu u 21
<210> 761
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 761
ncuucaugcc uuucuacagu uu 22
<210> 762
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 762
acuguagaaa ggcaugaagu u 21
<210> 763
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 763
nuuccugcuu caugccuuuc ua 22
<210> 764
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 764
uagaaaggca ugaagcagga auu 23
<210> 765
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 765
uuccugcuuc augccuuucu n 21
<210> 766
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 766
uagaaaggca ugaagcagga auu 23
<210> 767
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 767
nuuccugcuu caugccuuuc ua 22
<210> 768
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 768
uagaaaggca ugaagcagga auu 23
<210> 769
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 769
uuccugcuuc augccuuucu n 21
<210> 770
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 770
uagaaaggca ugaagcagga auu 23
<210> 771
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 771
nuuccugcuu caugccuuuc ua 22
<210> 772
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 772
uagaaaggca ugaagcagga auu 23
<210> 773
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 773
nuuccugcuu caugccuuuc ua 22
<210> 774
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 774
uagaaaggca ugaagcagga auu 23
<210> 775
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 775
nuuccugcuu caugccuuuc ua 22
<210> 776
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 776
uagaaaggca ugaagcagga auu 23
<210> 777
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 777
nuuccugcuu caugccuuuc ua 22
<210> 778
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 778
uagaaaggca ugaagcagga auu 23
<210> 779
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 779
nuuccugcuu caugccuuuc ua 22
<210> 780
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 780
uagaaaggca ugaagcagga auu 23
<210> 781
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 781
nuuccugcuu caugccuuuc ua 22
<210> 782
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 782
uagaaaggca ugaagcagga auu 23
<210> 783
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 783
nucaugccuu ucuacagugg cu 22
<210> 784
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 784
agccacugua gaaaggcaug auu 23
<210> 785
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 785
ucaugccuuu cuacaguggc n 21
<210> 786
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 786
agccacugua gaaaggcaug auu 23
<210> 787
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 787
nucaugccuu ucuacagugg cu 22
<210> 788
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 788
agccacugua gaaaggcaug auu 23
<210> 789
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 789
ucaugccuuu cuacaguggc n 21
<210> 790
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 790
agccacugua gaaaggcaug auu 23
<210> 791
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 791
nucaugccuu ucuacagugg cu 22
<210> 792
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 792
agccacugua gaaaggcaug auu 23
<210> 793
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 793
nucaugccuu ucuacagugg cu 22
<210> 794
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 794
agccacugua gaaaggcaug auu 23
<210> 795
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 795
ucaugccuuu cuacaguggc n 21
<210> 796
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 796
agccacugua gaaaggcaug auu 23
<210> 797
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 797
nucaugccuu ucuacagugg cu 22
<210> 798
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 798
agccacugua gaaaggcaug auu 23
<210> 799
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 799
nucaugccuu ucuacagugg cu 22
<210> 800
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 800
agccacugua gaaaggcaug auu 23
<210> 801
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 801
nucaugccuu ucuacagugg cu 22
<210> 802
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 802
agccacugua gaaaggcaug auu 23
<210> 803
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 803
nugcuucaug ccuuucuaca gu 22
<210> 804
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 804
acuguagaaa ggcaugaagc auu 23
<210> 805
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 805
ugcuucaugc cuuucuacag n 21
<210> 806
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 806
acuguagaaa ggcaugaagc auu 23
<210> 807
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 807
ugcuucaugc cuuucuacag n 21
<210> 808
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 808
acuguagaaa ggcaugaagc auu 23
<210> 809
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 809
nugcuucaug ccuuucuaca gu 22
<210> 810
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 810
acuguagaaa ggcaugaagc auu 23
<210> 811
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 811
ncuucaugcc uuucuacagu uu 22
<210> 812
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 812
acuguagaaa ggcaugaagu u 21
<210> 813
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 813
nugcuucaug ccuuucuaca gu 22
<210> 814
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 814
acuguagaaa ggcaugaagc auu 23
<210> 815
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 815
ngcuucaugc cuuucuacau uu 22
<210> 816
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 816
auguagaaag gcaugaagcu u 21
<210> 817
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 817
ncaugccuuu cuacaguggu uu 22
<210> 818
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 818
accacuguag aaaggcaugu u 21
<210> 819
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 819
ncugcuucau gccuuucuaa uu 22
<210> 820
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 820
uuagaaaggc augaagcagu u 21
<210> 821
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 821
ngcuucaugc cuuucuacaa uu 22
<210> 822
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 822
uuguagaaag gcaugaagcu u 21
<210> 823
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 823
nuucaugccu uucuacagua uu 22
<210> 824
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 824
uacuguagaa aggcaugaau u 21
<210> 825
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 825
nguuccugcu ucaugccuuu uu 22
<210> 826
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 826
aaaggcauga agcaggaacu u 21
<210> 827
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 827
auguuccugc uucaugccuu n 21
<210> 828
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 828
aaaggcauga agcaggaaca uuu 23
<210> 829
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 829
nauguuccug cuucaugccu uu 22
<210> 830
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 830
aaaggcauga agcaggaaca uuu 23
<210> 831
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 831
nguuccugcu ucaugccuuu uu 22
<210> 832
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 832
aaaggcauga agcaggaacu u 21
<210> 833
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 833
auguuccugc uucaugccuu n 21
<210> 834
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 834
aaaggcauga agcaggaaca uuu 23
<210> 835
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 835
nauguuccug cuucaugccu uu 22
<210> 836
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 836
aaaggcauga agcaggaaca uuu 23
<210> 837
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 837
nguuccugcu ucaugccuuu uu 22
<210> 838
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 838
aaaggcauga agcaggaacu u 21
<210> 839
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 839
auguuccugc uucaugccuu n 21
<210> 840
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 840
aaaggcauga agcaggaaca uuu 23
<210> 841
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 841
nauguuccug cuucaugccu uu 22
<210> 842
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 842
aaaggcauga agcaggaaca uuu 23
<210> 843
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 843
nauguuccug cuucaugccu uu 22
<210> 844
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 844
aaaggcauga agcaggaaca uuu 23
<210> 845
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 845
nauguuccug cuucaugccu uu 22
<210> 846
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 846
aaaggcauga agcaggaaca uuu 23
<210> 847
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 847
ngcuucaugc cuuucuacag ua 22
<210> 848
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 848
uacuguagaa aggcaugaag cuu 23
<210> 849
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 849
ngcuucaugc cuuucuacag ua 22
<210> 850
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 850
uacuguagaa aggcaugaag cuu 23
<210> 851
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 851
nuucaugccu uucuacagua uu 22
<210> 852
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 852
uacuguagaa aggcaugaau u 21
<210> 853
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 853
ngcuucaugc cuuucuacag ua 22
<210> 854
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 854
uacuguagaa aggcaugaag cuu 23
<210> 855
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 855
gcuucaugcc uuucuacagu n 21
<210> 856
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 856
uacuguagaa aggcaugaag cuu 23
<210> 857
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 857
ngcggcuucc ugggcuucua uu 22
<210> 858
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 858
uagaagccca ggaagccgcu u 21
<210> 859
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 859
nauggcuucc agauaugccu uu 22
<210> 860
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 860
aggcauaucu ggaagccauu u 21
<210> 861
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 861
nacauggcuu ccagauaugc cu 22
<210> 862
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 862
aggcauaucu ggaagccaug uuu 23
<210> 863
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 863
nacauggcuu ccagauaugc cu 22
<210> 864
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 864
aggcauaucu ggaagccaug uuu 23
<210> 865
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 865
ncaacguacc cuucauugau gu 22
<210> 866
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 866
acaucaauga aggguacguu guu 23
<210> 867
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 867
ncaacguacc cuucauugau gu 22
<210> 868
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 868
acaucaauga aggguacguu guu 23
<210> 869
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 869
nacguacccu ucauugaugu uu 22
<210> 870
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 870
acaucaauga aggguacguu u 21
<210> 871
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 871
cugcuucaug ccuuucuaca n 21
<210> 872
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 872
auguagaaag gcaugaagca guu 23
<210> 873
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 873
ncugcuucau gccuuucuac au 22
<210> 874
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 874
auguagaaag gcaugaagca guu 23
<210> 875
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 875
ngcuucaugc cuuucuacau uu 22
<210> 876
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 876
auguagaaag gcaugaagcu u 21
<210> 877
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 877
cugcuucaug ccuuucuaca n 21
<210> 878
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 878
auguagaaag gcaugaagca guu 23
<210> 879
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 879
ncugcuucau gccuuucuac au 22
<210> 880
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 880
auguagaaag gcaugaagca guu 23
<210> 881
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 881
cugcuucaug ccuuucuaca n 21
<210> 882
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 882
auguagaaag gcaugaagca guu 23
<210> 883
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 883
ncugcuucau gccuuucuac an 22
<210> 884
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 884
auguagaaag gcaugaagca guu 23
<210> 885
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 885
ngcuucaugc cuuucuacau uu 22
<210> 886
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 886
auguagaaag gcaugaagcu u 21
<210> 887
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 887
ncuucaugcc uuucuacagu uu 22
<210> 888
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 888
acuguagaaa ggcaugaagu u 21
<210> 889
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 889
ugcuucaugc cuuucuacag n 21
<210> 890
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 890
acuguagaaa ggcaugaagc auu 23
<210> 891
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 891
ncugcuucau gccuuucuac au 22
<210> 892
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 892
auguagaaag gcaugaagca guu 23
<210> 893
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 893
cugcuucaug ccuuucuaca n 21
<210> 894
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 894
auguagaaag gcaugaagca guu 23
<210> 895
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 895
cugcuucaug ccuuucuaca n 21
<210> 896
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 896
auguagaaag gcaugaagca guu 23
<210> 897
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 897
ncuucauccc uuucuacagu uu 22
<210> 898
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 898
acuguagaaa gggaugaagu u 21
<210> 899
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 899
ngcuucaucc cuuucuacau uu 22
<210> 900
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 900
auguagaaag ggaugaagcu u 21
<210> 901
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 901
ugcuucaucc cuuucuacag n 21
<210> 902
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 902
acuguagaaa gggaugaagc auu 23
<210> 903
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 903
cugcuucauc ccuuucuaca n 21
<210> 904
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 904
auguagaaag ggaugaagca guu 23
<210> 905
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 905
nacauugcuc uuucaccuga uu 22
<210> 906
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 906
ucaggugaaa gagcaauguu u 21
<210> 907
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 907
cugcuucaug ccuuucuaca n 21
<210> 908
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 908
auguagaaag gcaugaagca guu 23
<210> 909
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 909
cugcuucaug ccuuucuaca n 21
<210> 910
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 910
auguagaaag gcaugaagca guu 23
<210> 911
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 911
cugcuucaug ccuuucuaca n 21
<210> 912
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 912
auguagaaag gcaugaagca guu 23
<210> 913
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 913
cugcuucaug ccuuucuaca n 21
<210> 914
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 914
auguagaaag gcaugaagca guu 23
<210> 915
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 915
cugcuucaug ccuuucuaca n 21
<210> 916
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 916
auguagaaag gcaugaagca guu 23
<210> 917
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 917
cugcuucaug ccuuucuaca n 21
<210> 918
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 918
auguagaaag gcaugaagca guu 23
<210> 919
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 919
cugcuucaug ccuuucuaca n 21
<210> 920
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 920
auguagaaag gcaugaagca guu 23
<210> 921
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 921
cugcuucaug ccuuucuaca n 21
<210> 922
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 922
auguagaaag gcaugaagca guu 23
<210> 923
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 923
cugcuucaug ccuuucuaca n 21
<210> 924
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 924
auguagaaag gcaugaagca guu 23
<210> 925
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 925
cugcuucaug ccuuucuaca n 21
<210> 926
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 926
auguagaaag gcaugaagca guu 23
<210> 927
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 927
cugcuucaug ccuuucuaca n 21
<210> 928
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 928
auguagaaag gcaugaagca guu 23
<210> 929
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 929
ncuucaugcc tuucuacagu uu 22
<210> 930
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 930
acuguagaaa ggcaugaagu u 21
<210> 931
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 931
ncuucaugcc uuucuacagu uu 22
<210> 932
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 932
acuguagaaa ggcaugaagu u 21
<210> 933
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 933
ncuucaugcc uuucuacagu uu 22
<210> 934
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 934
acuguagaaa ggcaugaagu u 21
<210> 935
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 935
ncuucaugcc uuucuacagu uu 22
<210> 936
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 936
acuguagaaa ggcaugaagu u 21
<210> 937
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 937
ncuucaugcc uuucuacagu uu 22
<210> 938
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 938
acuguagaaa ggcaugaagu u 21
<210> 939
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 939
ncuucaugcc uuucuacagu uu 22
<210> 940
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 940
acuguagaaa ggcaugaagu u 21
<210> 941
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 941
ncuucaugcc utucuacagu uu 22
<210> 942
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 942
acuguagaaa ggcaugaagu u 21
<210> 943
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 943
ngcuucaugg gauucuacau uu 22
<210> 944
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 944
auguagaauc ccaugaagcu u 21
<210> 945
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 945
ncuucaugcg aaucuacagu uu 22
<210> 946
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 946
acuguagauu cgcaugaagu u 21
<210> 947
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 947
cugcuucaug ccuuucuaca n 21
<210> 948
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 948
uuguagaaag gcaugaagca guu 23
<210> 949
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 949
ncugcuucau gccuuucuac aa 22
<210> 950
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 950
uuguagaaag gcaugaagca guu 23
<210> 951
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 951
cugcuucaug ccuuucuaca a 21
<210> 952
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 952
uuguagaaag gcaugaagca guu 23
<210> 953
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 953
cugcuucaug ggauucuaca n 21
<210> 954
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 954
auguagaauc ccaugaagca guu 23
<210> 955
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 955
ncugcuucau gggauucuac au 22
<210> 956
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 956
auguagaauc ccaugaagca guu 23
<210> 957
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 957
ncuucaugcc uuucuacagu uu 22
<210> 958
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 958
acuguagaaa ggcaugaagu u 21
<210> 959
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 959
ncuucaugcc uuucuacagu uu 22
<210> 960
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 960
acuguagaaa ggcaugaagu u 21
<210> 961
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 961
ngcuucaugc cuuucuacau uu 22
<210> 962
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 962
auguagaaag gcaugaagcu u 21
<210> 963
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 963
nugcuucaug ccuuucuaca gn 22
<210> 964
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 964
acuguagaaa ggcaugaagc auu 23
<210> 965
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 965
ncuucaugcc uuucuacagu uu 22
<210> 966
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 966
acuguagaaa ggcaugaagu u 21
<210> 967
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 967
ugcuucaugc cuuucuacag n 21
<210> 968
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 968
acuguagaaa ggcaugaagc auu 23
<210> 969
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 969
ugcuucaugc cuuucuacag n 21
<210> 970
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 970
acuguagaaa ggcaugaagc auu 23
<210> 971
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 971
ugcuucaugc cuuucuacag n 21
<210> 972
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 972
acuguagaaa ggcaugaagc auu 23
<210> 973
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 973
ncuucaugcc uuucuacagu uu 22
<210> 974
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 974
acuguagaaa ggcaugaagu u 21
<210> 975
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 975
ugcuucaugc cuuucuacag n 21
<210> 976
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 976
acuguagaaa ggcaugaagc auu 23
<210> 977
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 977
augccuuucu acaguggcuu n 21
<210> 978
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 978
agccacugua gaaaggcaug auu 23
<210> 979
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 979
ucaugccuuu cuacaguggc n 21
<210> 980
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 980
agccacugua gaaaggcaug auu 23
<210> 981
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 981
naugccuuuc uacaguggcu uu 22
<210> 982
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 982
agccacugua gaaaggcauu u 21
<210> 983
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 983
naugccuuuc uacaguggcu uu 22
<210> 984
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 984
agccacugua gaaaggcauu u 21
<210> 985
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 985
nucaugccuu ucuacagugg cu 22
<210> 986
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 986
agccacugua gaaaggcaug auu 23
<210> 987
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 987
ucaugccuuu cuacaguggc n 21
<210> 988
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 988
agccacugua gaaaggcaug auu 23
<210> 989
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 989
naugccuuuc uacaguggcu uu 22
<210> 990
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 990
agccacugua gaaaggcauu u 21
<210> 991
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 991
ucaugccuuu cuacaguggc n 21
<210> 992
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 992
agccacugua gaaaggcaug auu 23
<210> 993
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 993
ucaugccuuu cuacaguggc n 21
<210> 994
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 994
agccacugua gaaaggcaug auu 23
<210> 995
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 995
nucaugccuu ucuacagugg cn 22
<210> 996
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 996
agccacugua gaaaggcaug auu 23
<210> 997
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 997
naugccuuuc uacaguggca uu 22
<210> 998
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 998
ugccacugua gaaaggcauu u 21
<210> 999
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 999
ucaugccuuu cuacaguggc n 21
<210> 1000
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1000
ugccacugua gaaaggcaug auu 23
<210> 1001
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1001
nucaugccuu ucuacagugg ca 22
<210> 1002
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1002
ugccacugua gaaaggcaug auu 23
<210> 1003
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1003
ucaugccuuu cuacaguggc a 21
<210> 1004
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1004
ugccacugua gaaaggcaug auu 23
<210> 1005
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1005
cugcuucaug ccuuucuaca n 21
<210> 1006
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1006
auguagaaag gcaugaagca guu 23
<210> 1007
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1007
cugcuucaug ccuuucuaca n 21
<210> 1008
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1008
uuguagaaag gcaugaagca guu 23
<210> 1009
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1009
cugcuucaug ccuuucuaca a 21
<210> 1010
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1010
uuguagaaag gcaugaagca guu 23
<210> 1011
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1011
ucaugccuuu cuacaguggc n 21
<210> 1012
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1012
ugccacugua gaaaggcaug auu 23
<210> 1013
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1013
ucaugccuuu cuacaguggc a 21
<210> 1014
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1014
ugccacugua gaaaggcaug auu 23
<210> 1015
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1015
ncuucaugcc uuucuacagu uu 22
<210> 1016
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1016
acuguagaaa ggcaugaagu u 21
<210> 1017
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1017
cugcuucaug ccuuucuaca n 21
<210> 1018
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1018
auguanaaag gcaugaagca guu 23
<210> 1019
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1019
cugcuucaug ccuuucuaca n 21
<210> 1020
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1020
auguanaaag gcaugaagca guu 23
<210> 1021
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1021
ugcuucaugc cuuucuacag n 21
<210> 1022
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1022
acugungaaa ggcaugaagc auu 23
<210> 1023
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1023
ugcuucaugc cuuucuacag n 21
<210> 1024
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1024
acugungaaa ggcaugaagc auu 23
<210> 1025
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1025
ucaugccuuu cuacaguggc n 21
<210> 1026
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1026
agccanugua gaaaggcaug auu 23
<210> 1027
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1027
ucaugccuuu cuacaguggc n 21
<210> 1028
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1028
agccanugua gaaaggcaug auu 23
<210> 1029
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1029
cugcuucaug ccuuucuaca n 21
<210> 1030
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1030
auguagaaag gcaugaagca guu 23
<210> 1031
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1031
cugcuucaug ccuuucuaca n 21
<210> 1032
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1032
auguagaaag gcaugaagca guu 23
<210> 1033
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1033
cugcuucaug ccuuucuaca n 21
<210> 1034
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1034
auguagaaag gcaugaagca guu 23
<210> 1035
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1035
cugcuucaug ccuuucuaca n 21
<210> 1036
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1036
auguagaaag gcaugaagca guu 23
<210> 1037
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1037
cugcuucaug ccuuucuaca n 21
<210> 1038
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1038
auguagaaag gcaugaagca guu 23
<210> 1039
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1039
cugcuucaug ccuuucuaca n 21
<210> 1040
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1040
auguagaaag gcaugaagca guu 23
<210> 1041
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1041
cugcuucaug ccuuucuaca n 21
<210> 1042
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1042
auguagaaag gcaugaagca guu 23
<210> 1043
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1043
ncugcuucau gccuuucuac au 22
<210> 1044
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1044
auguagaaag gcaugaagca guu 23
<210> 1045
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 1045
ncugcuucau gccuuucuac an 22
<210> 1046
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1046
auguagaaag gcaugaagca guu 23
<210> 1047
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1047
cugcuucaug ccuuucuaca n 21
<210> 1048
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1048
auguagaaag gcaugaagca guu 23
<210> 1049
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1049
cugcuucaug ccuuucuaca n 21
<210> 1050
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1050
auguagaaag gcaugaagca guu 23
<210> 1051
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1051
ncugcuucau gccuuucuac au 22
<210> 1052
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1052
auguagaaag gcaugaagca guu 23
<210> 1053
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1053
cugcuucaug ccuuucuaca n 21
<210> 1054
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1054
auguagaaag gcaugaagca guu 23
<210> 1055
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1055
cugcuucaug ccuuucuaca n 21
<210> 1056
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1056
auguagaaag gcaugaagca guu 23
<210> 1057
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1057
ncugcuucau gccuuucuac au 22
<210> 1058
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1058
auguagaaag gcaugaagca guu 23
<210> 1059
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 1059
ncugcuucau gccuuucuac an 22
<210> 1060
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1060
auguagaaag gcaugaagca guu 23
<210> 1061
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1061
cugcuucaug ccuuucuaca n 21
<210> 1062
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (2)..(2)
<223> Abasic nucleotide
<400> 1062
anguagaaag gcaugaagca guu 23
<210> 1063
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1063
cugcuucaug ccuuucuaca n 21
<210> 1064
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (3)..(3)
<223> Abasic nucleotide
<400> 1064
aunuagaaag gcaugaagca guu 23
<210> 1065
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1065
cugcuucaug ccuuucuaca n 21
<210> 1066
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (4)..(4)
<223> Abasic nucleotide
<400> 1066
augnagaaag gcaugaagca guu 23
<210> 1067
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1067
cugcuucaug ccuuucuaca n 21
<210> 1068
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (5)..(5)
<223> Abasic nucleotide
<400> 1068
augungaaag gcaugaagca guu 23
<210> 1069
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1069
cugcuucaug ccuuucuaca n 21
<210> 1070
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (7)..(7)
<223> Abasic nucleotide
<400> 1070
auguagnaag gcaugaagca guu 23
<210> 1071
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1071
cugcuucaug ccuuucuaca n 21
<210> 1072
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (8)..(8)
<223> Abasic nucleotide
<400> 1072
auguaganag gcaugaagca guu 23
<210> 1073
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1073
caacguaccc uucauugaug n 21
<210> 1074
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1074
acaucaauga aggguacguu guu 23
<210> 1075
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1075
caacguaccc uucauugaug n 21
<210> 1076
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1076
acaucaauga aggguacguu guu 23
<210> 1077
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1077
acauggcuuc cagauaugcc n 21
<210> 1078
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1078
aggcauaucu ggaagccaug uuu 23
<210> 1079
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1079
acauggcuuc cagauaugcc n 21
<210> 1080
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1080
aggcauaucu ggaagccaug uuu 23
<210> 1081
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1081
cugcuucaug ccuuucuaca n 21
<210> 1082
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1082
auguagaaag gcaugaagca guu 23
<210> 1083
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1083
cugcuucaug ccuuucuaca n 21
<210> 1084
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1084
auguagaaag gcaugaagca guu 23
<210> 1085
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1085
cugcuucaug ccuuucuaca n 21
<210> 1086
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1086
auguagaaag gcaugaagca guu 23
<210> 1087
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1087
cugcggcuuc cugggcuucu n 21
<210> 1088
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1088
uagaagccca ggaagccgca guu 23
<210> 1089
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1089
cugcggcuuc cugggcuucu n 21
<210> 1090
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1090
uagaagccca ggaagccgca guu 23
<210> 1091
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1091
ugcuucaugc cuuucuacag n 21
<210> 1092
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1092
acuguagaaa ggcaugaagc auu 23
<210> 1093
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1093
nugcuucaug ccuuucuaca gu 22
<210> 1094
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1094
acuguagaaa ggcaugaagc auu 23
<210> 1095
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 1095
nugcuucaug ccuuucuaca gn 22
<210> 1096
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1096
acuguagaaa ggcaugaagc auu 23
<210> 1097
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1097
ugcuucaugc cuuucuacag n 21
<210> 1098
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1098
acuguagaaa ggcaugaagc auu 23
<210> 1099
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1099
ugcuucaugc cuuucuacag n 21
<210> 1100
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1100
acuguagaaa ggcaugaagc auu 23
<210> 1101
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1101
ugcuucaugc cuuucuacag n 21
<210> 1102
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1102
acuguagaaa ggcaugaagc auu 23
<210> 1103
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1103
cugcuucaug ccuuucuaca u 21
<210> 1104
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1104
auguagaaag gcaugaagca guu 23
<210> 1105
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1105
cugcuucaug ccuuucuaca u 21
<210> 1106
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1106
auguagaaag gcaugaagca guu 23
<210> 1107
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1107
cugcuucaug ccuuucuaca u 21
<210> 1108
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1108
auguagaaag gcaugaagca guu 23
<210> 1109
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1109
ugcuucaugc cuuucuacag n 21
<210> 1110
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1110
ucuguagaaa ggcaugaagc auu 23
<210> 1111
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1111
ugcuucaugc cuuucuacag a 21
<210> 1112
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1112
ucuguagaaa ggcaugaagc auu 23
<210> 1113
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1113
cugcuucaug ccuuucuaca t 21
<210> 1114
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1114
auguagaaag gcaugaagca guu 23
<210> 1115
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1115
cugcuucaug ccuuucuaca n 21
<210> 1116
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1116
auguagaaag gcaugaagca guu 23
<210> 1117
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1117
cugcuucaug ccuuucuaca n 21
<210> 1118
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1118
auguagaaag gcaugaagca guu 23
<210> 1119
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1119
cugcuucaug ccuuucuaca n 21
<210> 1120
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1120
auguagaaag gcaugaagca guu 23
<210> 1121
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1121
cugcuucaug ccuuucuaca n 21
<210> 1122
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1122
auguagaaag gcaugaagca guu 23
<210> 1123
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1123
cugcuucaug ccuuucuaca n 21
<210> 1124
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1124
auguagaaag gcaugaagca guu 23
<210> 1125
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1125
cugcuucaug ccuuucuaca n 21
<210> 1126
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1126
auguagaaag gcaugaagca guu 23
<210> 1127
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1127
cugcuucaug ccuuucuaca n 21
<210> 1128
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1128
auguagaaag gcaugaagca guu 23
<210> 1129
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1129
cugcuucaug ccuuucuaca n 21
<210> 1130
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1130
auguagaaag gcaugaagca guu 23
<210> 1131
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1131
cugcuucaug ccuuucuaca n 21
<210> 1132
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1132
auguagaaag gcaugaagca guu 23
<210> 1133
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1133
cugcuucaug ccuuucuaca n 21
<210> 1134
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1134
auguagaaag gcaugaagca guu 23
<210> 1135
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1135
cugcuucaug ccuuucuaca n 21
<210> 1136
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1136
auguagaaag gcaugaagca guu 23
<210> 1137
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1137
cugcuucaug ccuuucuaca n 21
<210> 1138
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1138
auguagaaag gcaugaagca guu 23
<210> 1139
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1139
cugcuucaug ccuuucuaca n 21
<210> 1140
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1140
auguagaaag gcaugaagca guu 23
<210> 1141
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1141
cugcuucaug ccuuucuaca n 21
<210> 1142
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1142
auguagaaag gcaugaagca guu 23
<210> 1143
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1143
cugcuucaug ccuuucuaca n 21
<210> 1144
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1144
auguagaaag gcaugaagca guu 23
<210> 1145
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1145
cugcuucaug ccuuucuaca n 21
<210> 1146
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1146
auguagaaag gcaugaagca guu 23
<210> 1147
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1147
cugcuucaug ccuuucuaca n 21
<210> 1148
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1148
auguagaaag gcaugaagca guu 23
<210> 1149
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1149
cugcuucaug ccuuucuaca n 21
<210> 1150
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1150
auguagaaag gcaugaagca guu 23
<210> 1151
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1151
cugcuucaug ccuuucuaca n 21
<210> 1152
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1152
auguagaaag gcaugaagca guu 23
<210> 1153
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1153
cugcuucaug ccuuucuaca n 21
<210> 1154
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1154
auguagaaag gcaugaagca guu 23
<210> 1155
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1155
cugcuucaug ccuuucuaca n 21
<210> 1156
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1156
auguagaaag gcaugaagca guu 23
<210> 1157
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1157
cugcuucaug ccuuucuaca n 21
<210> 1158
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1158
auguagaaag gcaugaagca guu 23
<210> 1159
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1159
cugcuucaug ccuuucuaca n 21
<210> 1160
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1160
auguagaaag gcaugaagca guu 23
<210> 1161
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1161
cugcuucaug ccuuucuaca n 21
<210> 1162
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1162
auguagaaag gcaugaagca guu 23
<210> 1163
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1163
cugcuucaug ccuuucuaca n 21
<210> 1164
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1164
auguagaaag gcaugaagca guu 23
<210> 1165
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1165
cugcuucaug ccuuucuaca n 21
<210> 1166
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1166
auguagaaag gcaugaagca guu 23
<210> 1167
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1167
cugcuucaug ccuuucuaca n 21
<210> 1168
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1168
auguagaaag gcaugaagca guu 23
<210> 1169
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1169
ugcuucaugc cuuucuacag a 21
<210> 1170
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1170
ucuguagaaa ggcaugaagc auu 23
<210> 1171
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1171
ugcuucaugc cuuucuacag a 21
<210> 1172
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1172
ucuguagaaa ggcaugaagc auu 23
<210> 1173
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1173
ugcuucaugc cuuucuacag a 21
<210> 1174
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1174
ucuguagaaa ggcaugaagc auu 23
<210> 1175
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1175
ugcuucaugc cuuucuacag a 21
<210> 1176
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1176
ucuguagaaa ggcaugaagc auu 23
<210> 1177
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1177
ugcuucaugc cuuucuacag a 21
<210> 1178
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1178
ucuguagaaa ggcaugaagc auu 23
<210> 1179
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1179
ugcuucaugc cuuucuacag a 21
<210> 1180
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (2)..(2)
<223> Abasic nucleotide
<400> 1180
unuguagaaa ggcaugaagc auu 23
<210> 1181
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1181
ugcuucaugc cuuucuacag a 21
<210> 1182
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (3)..(3)
<223> Abasic nucleotide
<400> 1182
ucnguagaaa ggcaugaagc auu 23
<210> 1183
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1183
ugcuucaugc cuuucuacag a 21
<210> 1184
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (4)..(4)
<223> Abasic nucleotide
<400> 1184
ucunuagaaa ggcaugaagc auu 23
<210> 1185
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1185
ugcuucaugc cuuucuacag a 21
<210> 1186
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (5)..(5)
<223> Abasic nucleotide
<400> 1186
ucugnagaaa ggcaugaagc auu 23
<210> 1187
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1187
ugcuucaugc cuuucuacag a 21
<210> 1188
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1188
ucugungaaa ggcaugaagc auu 23
<210> 1189
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1189
ugcuucaugc cuuucuacag a 21
<210> 1190
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (7)..(7)
<223> Abasic nucleotide
<400> 1190
ucuguanaaa ggcaugaagc auu 23
<210> 1191
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1191
ugcuucaugc cuuucuacag a 21
<210> 1192
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (8)..(8)
<223> Abasic nucleotide
<400> 1192
ucuguagnaa ggcaugaagc auu 23
<210> 1193
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1193
ucaugccuuu cuacaguggc t 21
<210> 1194
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1194
agccacugua gaaaggcaug auu 23
<210> 1195
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1195
ucaugccuuu cuacaguggc n 21
<210> 1196
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1196
ugccacugua gaaaggcaug auu 23
<210> 1197
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1197
ucaugccuuu cuacaguggc a 21
<210> 1198
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1198
ugccacugua gaaaggcaug auu 23
<210> 1199
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1199
uccugcuuca ugccuuucua t 21
<210> 1200
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1200
auagaaaggc augaagcagg auu 23
<210> 1201
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1201
uccugcuuca ugccuuucua n 21
<210> 1202
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1202
uuagaaaggc augaagcagg auu 23
<210> 1203
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1203
uccugcuuca ugccuuucua a 21
<210> 1204
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1204
uuagaaaggc augaagcagg auu 23
<210> 1205
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1205
uauguuccug cuucaugccu t 21
<210> 1206
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1206
aaggcaugaa gcaggaacau auu 23
<210> 1207
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1207
uauguuccug cuucaugccu n 21
<210> 1208
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1208
uaggcaugaa gcaggaacau auu 23
<210> 1209
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1209
uauguuccug cuucaugccu a 21
<210> 1210
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1210
uaggcaugaa gcaggaacau auu 23
<210> 1211
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1211
uccugcuuca ugccuuucua n 21
<210> 1212
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1212
auagaaaggc augaagcagg auu 23
<210> 1213
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1213
uauguuccug cuucaugccu n 21
<210> 1214
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1214
aaggcaugaa gcaggaacau auu 23
<210> 1215
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1215
ucaugccuuu cuacaguggc t 21
<210> 1216
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1216
agccacugua gaaaggcaug auu 23
<210> 1217
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1217
uccugcuuca ugccuuucua t 21
<210> 1218
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1218
auagaaaggc augaagcagg auu 23
<210> 1219
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1219
uccugcuuca ugccuuucua a 21
<210> 1220
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1220
uuagaaaggc augaagcagg auu 23
<210> 1221
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1221
uauguuccug cuucaugccu a 21
<210> 1222
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1222
uaggcaugaa gcaggaacau auu 23
<210> 1223
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1223
ugcuucaugc cuuucuacag a 21
<210> 1224
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1224
ucuguagaaa ggcaugaagc auu 23
<210> 1225
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1225
cugcuucaug ccuuucuaca n 21
<210> 1226
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1226
auguagaaag gcaugaagca guu 23
<210> 1227
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1227
cugcuucaug ccuuucuaca n 21
<210> 1228
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1228
auguagaaag gcaugaagca guu 23
<210> 1229
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1229
cugcuucaug ccuuucuaca n 21
<210> 1230
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1230
auguagaaag gcaugaagca guu 23
<210> 1231
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1231
cugcuucaug ccuuucuaca n 21
<210> 1232
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1232
auguagaaag gcaugaagca guu 23
<210> 1233
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1233
cugcuucaug ccuuucuaca n 21
<210> 1234
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1234
auguagaaag gcaugaagca guu 23
<210> 1235
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1235
cugcuucaug ccuuucuaca n 21
<210> 1236
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1236
auguagaaag gcaugaagca guu 23
<210> 1237
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1237
cugcuucaug ccuuucuaca n 21
<210> 1238
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1238
auguagaaag gcaugaagca guu 23
<210> 1239
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1239
cugcuucaug ccuuucuaca n 21
<210> 1240
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1240
auguagaaag gcaugaagca guu 23
<210> 1241
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1241
cugcuucaug ccuuucuaca n 21
<210> 1242
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1242
auguagaaag gcaugaagca guu 23
<210> 1243
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1243
cugcuucaug ccutucuaca n 21
<210> 1244
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1244
auguagaaag gcaugaagca guu 23
<210> 1245
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1245
cugcuucaug cctuucuaca n 21
<210> 1246
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1246
auguagaaag gcaugaagca guu 23
<210> 1247
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1247
cugcuucaug ccuutcuaca n 21
<210> 1248
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1248
auguagaaag gcaugaagca guu 23
<210> 1249
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1249
cugcuucaug ccuuuctaca n 21
<210> 1250
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1250
auguagaaag gcaugaagca guu 23
<210> 1251
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1251
cugcuucaug ccuuucuaca n 21
<210> 1252
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1252
auguagaaag gcaugaagca guu 23
<210> 1253
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1253
cugcuucaug ccuuucuaca n 21
<210> 1254
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1254
auguagaaag gcaugaagca guu 23
<210> 1255
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1255
cugcuucaug ccuutcuaca n 21
<210> 1256
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (7)..(7)
<223> Abasic nucleotide
<400> 1256
auguagnaag gcaugaagca guu 23
<210> 1257
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1257
cugcuucaug ccuuuctaca n 21
<210> 1258
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (5)..(5)
<223> Abasic nucleotide
<400> 1258
augungaaag gcaugaagca guu 23
<210> 1259
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1259
cugcuucaug ccuuucuaca n 21
<210> 1260
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (4)..(4)
<223> Abasic nucleotide
<400> 1260
augnagaaag gcaugaagca guu 23
<210> 1261
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1261
cugcuucaug ccuuucuaca n 21
<210> 1262
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1262
auguagaaag gcaugaagca guu 23
<210> 1263
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1263
cugcuucaug ccuuucuaca n 21
<210> 1264
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1264
auguagaaag gcaugaagca guu 23
<210> 1265
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1265
cugcuucaug ccutucuaca n 21
<210> 1266
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1266
auguagaaag gcaugaagca guu 23
<210> 1267
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1267
cugcuucaug ccutucuaca n 21
<210> 1268
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1268
auguagaaag gcaugaagca guu 23
<210> 1269
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1269
cugcuucaug ccutucuaca n 21
<210> 1270
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1270
auguagaaag gcaugaagca guu 23
<210> 1271
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1271
cugcuucaug ccutucuaca n 21
<210> 1272
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1272
auguagaaag gcaugaagca guu 23
<210> 1273
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1273
ugcuucaugc cuuucuacag a 21
<210> 1274
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (5)..(5)
<223> Abasic nucleotide
<400> 1274
ucugnagaaa ggcaugaagc auu 23
<210> 1275
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1275
ugcuucaugc cuuuctacag a 21
<210> 1276
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1276
ucugungaaa ggcaugaagc auu 23
<210> 1277
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1277
ugcuucaugc cuutcuacag a 21
<210> 1278
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (8)..(8)
<223> Abasic nucleotide
<400> 1278
ucuguagnaa ggcaugaagc auu 23
<210> 1279
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1279
ugcuucaugc cuuucuacag a 21
<210> 1280
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1280
ucuguagaaa ggcaugaagc auu 23
<210> 1281
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1281
ugcuucaugc cuuucuacag a 21
<210> 1282
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1282
ucuguagaaa ggcaugaagc auu 23
<210> 1283
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1283
ugcuucaugc cuuuctacag a 21
<210> 1284
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1284
ucuguagaaa ggcaugaagc auu 23
<210> 1285
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1285
ugcuucaugc cuuucuacag a 21
<210> 1286
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (2)..(2)
<223> Abasic nucleotide
<400> 1286
unuguagaaa ggcaugaagc auu 23
<210> 1287
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1287
ugcuucaugc cuuucuacag a 21
<210> 1288
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (3)..(3)
<223> Abasic nucleotide
<400> 1288
ucnguagaaa ggcaugaagc auu 23
<210> 1289
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1289
ucaugccuuu cuacaguggc n 21
<210> 1290
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1290
agccanugua gaaaggcaug auu 23
<210> 1291
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1291
ucaugccuuu cuacagtggc n 21
<210> 1292
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1292
agccanugua gaaaggcaug auu 23
<210> 1293
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1293
ucaugccuuu cuacaguggc n 21
<210> 1294
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1294
agccanugua gaaaggcaug auu 23
<210> 1295
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1295
ggaaagacug uuccaaaaau u 21
<210> 1296
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1296
uuuuuggaac agucuuuccu u 21
<210> 1297
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1297
gguauguucc ugcuucaugu u 21
<210> 1298
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1298
caugaagcag gaacauaccu u 21
<210> 1299
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1299
guauguuccu gcuucaugcu u 21
<210> 1300
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1300
gcaugaagca ggaacauacu u 21
<210> 1301
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1301
uguuccugcu ucaugcccuu u 21
<210> 1302
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1302
agggcaugaa gcaggaacau u 21
<210> 1303
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1303
gcuucaugcc cuucuacagu u 21
<210> 1304
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1304
cuguagaagg gcaugaagcu u 21
<210> 1305
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1305
cuucaugccc uucuacaguu u 21
<210> 1306
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1306
acuguagaag ggcaugaagu u 21
<210> 1307
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1307
gcggcuuccu gggcuucuau u 21
<210> 1308
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1308
uagaagccca ggaagccgcu u 21
<210> 1309
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1309
guuccugcuu caugcccuuu u 21
<210> 1310
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1310
aagggcauga agcaggaacu u 21
<210> 1311
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1311
auggcuucca gauaugccuu u 21
<210> 1312
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1312
aggcauaucu ggaagccauu u 21
<210> 1313
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1313
ccugcuucau gcccuucuau u 21
<210> 1314
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1314
uagaagggca ugaagcaggu u 21
<210> 1315
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1315
uucaugcccu ucuacaguuu u 21
<210> 1316
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1316
aacuguagaa gggcaugaau u 21
<210> 1317
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1317
uucaugcccu ucuacagugu u 21
<210> 1318
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1318
cacuguagaa gggcaugaau u 21
<210> 1319
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1319
gcuucaugcc cuucuacauu u 21
<210> 1320
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1320
auguagaagg gcaugaagcu u 21
<210> 1321
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1321
gguccagccu gaacuucuuu u 21
<210> 1322
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1322
aagaaguuca ggcuggaccu u 21
<210> 1323
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1323
gcggcuuccu gggcuucuau u 21
<210> 1324
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1324
uagaagccca ggaagccgcu u 21
<210> 1325
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1325
gcggcuuccu gggcuucuau u 21
<210> 1326
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1326
uagaagccca ggaagccgcu u 21
<210> 1327
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1327
guuccugcuu caugcccuuu u 21
<210> 1328
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1328
aagggcauga agcaggaacu u 21
<210> 1329
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1329
guuccugcuu caugcccuuu u 21
<210> 1330
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1330
aagggcauga agcaggaacu u 21
<210> 1331
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1331
ccugcuucau gcccuucuau u 21
<210> 1332
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1332
uagaagggca ugaagcaggu u 21
<210> 1333
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1333
ccugcuucau gcccuucuau u 21
<210> 1334
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1334
uagaagggca ugaagcaggu u 21
<210> 1335
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1335
augcccuucu acaguggccu u 21
<210> 1336
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1336
ggccacugua gaagggcauu u 21
<210> 1337
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1337
auggcuucca gauaugccuu u 21
<210> 1338
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1338
aggcauaucu ggaagccauu u 21
<210> 1339
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1339
gugacaacgu acccuucauu u 21
<210> 1340
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1340
augaagggua cguugucacu u 21
<210> 1341
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1341
guauguuccu gcuucaugcu u 21
<210> 1342
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1342
gcaugaagca ggaacauacu u 21
<210> 1343
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1343
guauguuccu gcuucaugcu u 21
<210> 1344
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1344
gcaugaagca ggaacauacu u 21
<210> 1345
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1345
guauguuccu gcuucaugcu u 21
<210> 1346
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1346
gcaugaagca ggaacauacu u 21
<210> 1347
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1347
guauguuccu gcuucaugcc u 21
<210> 1348
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1348
aggcaugaag caggaacaua cuu 23
<210> 1349
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1349
ugguauguuc cugcuucaug u 21
<210> 1350
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1350
gcaugaagca ggaacauacc auu 23
<210> 1351
<211> 19
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1351
guauguuccu gcuucaugu 19
<210> 1352
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1352
gcaugaagca ggaacauacu u 21
<210> 1353
<211> 20
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (20)..(20)
<223> Inverted abasic nucleotide
<400> 1353
guauguuccu gcuucaugcn 20
<210> 1354
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1354
gcaugaagca ggaacauacu u 21
<210> 1355
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1355
gcuucaugcc cuucuacauu u 21
<210> 1356
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1356
auguagaagg gcaugaagcu u 21
<210> 1357
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1357
gcuucaugcc cuucuacauu u 21
<210> 1358
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1358
auguagaagg gcaugaagcu u 21
<210> 1359
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1359
gcuucaugcc cuucuacauu u 21
<210> 1360
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1360
auguagaagg gcaugaagcu u 21
<210> 1361
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1361
gcuucaugcc cuucuacauu u 21
<210> 1362
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1362
auguagaagg gcaugaagcu u 21
<210> 1363
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1363
gcuucaugcc cuucuacauu u 21
<210> 1364
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1364
auguagaagg gcaugaagcu u 21
<210> 1365
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1365
gcuucaugcc cuucuacauu u 21
<210> 1366
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1366
auguagaagg gcaugaagcu u 21
<210> 1367
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1367
gcuucaugcc cuucuacauu u 21
<210> 1368
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1368
auguagaagg gcaugaagcu u 21
<210> 1369
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1369
gcuucaugcc cuucuacauu u 21
<210> 1370
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1370
auguagaagg gcaugaagcu u 21
<210> 1371
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1371
gcuucaugcc cuucuacauu u 21
<210> 1372
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1372
auguagaagg gcaugaagcu u 21
<210> 1373
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1373
gcuucaugcc cuucuacauu u 21
<210> 1374
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1374
auguagaagg gcaugaagcu u 21
<210> 1375
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1375
gcuucaugcc cuucuacauu u 21
<210> 1376
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1376
auguagaagg gcaugaagcu u 21
<210> 1377
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1377
gcuucaugcc cuucuacauu u 21
<210> 1378
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1378
auguagaagg gcaugaagcu u 21
<210> 1379
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1379
gcuucaugcc cuucuacauu u 21
<210> 1380
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1380
auguagaagg gcaugaagcu u 21
<210> 1381
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1381
gcuucaugcc cuucuacauu u 21
<210> 1382
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1382
auguagaagg gcaugaagcu u 21
<210> 1383
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1383
gcuucaugcc cuucuacauu u 21
<210> 1384
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1384
auguagaagg gcaugaagcu u 21
<210> 1385
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1385
gcuucaugcc cuucuacauu u 21
<210> 1386
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1386
auguagaagg gcaugaagcu u 21
<210> 1387
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1387
gcuucaugcc cuucuacauu u 21
<210> 1388
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1388
auguagaagg gcaugaagcu u 21
<210> 1389
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1389
gcuucaugcc cuucuacauu u 21
<210> 1390
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1390
auguagaagg gcaugaagcu u 21
<210> 1391
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1391
gcuucaugcc cuucuacauu u 21
<210> 1392
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1392
auguagaagg gcaugaagcu u 21
<210> 1393
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1393
gcuucaugcc cuucuacauu u 21
<210> 1394
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1394
auguagaagg gcaugaagcu u 21
<210> 1395
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1395
gcuucaugcc cuucuacauu u 21
<210> 1396
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1396
auguagaagg gcaugaagcu u 21
<210> 1397
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1397
gcuucaugcc cuucuacauu u 21
<210> 1398
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1398
auguagaagg gcaugaagcu u 21
<210> 1399
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1399
gcuucaugcc cuucuacauu u 21
<210> 1400
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1400
auguagaagg gcaugaagcu u 21
<210> 1401
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1401
gcuucaugcc cuucuacauu u 21
<210> 1402
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1402
auguagaagg gcaugaagcu u 21
<210> 1403
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1403
gcuucaugcc cuucuacagu u 21
<210> 1404
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1404
aacuguagaa gggcaugaag cuu 23
<210> 1405
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1405
cugcuucaug cccuucuaca u 21
<210> 1406
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1406
auguagaagg gcaugaagca guu 23
<210> 1407
<211> 19
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1407
gcuucaugcc cuucuacau 19
<210> 1408
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1408
auguagaagg gcaugaagcu u 21
<210> 1409
<211> 20
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (20)..(20)
<223> Inverted abasic nucleotide
<400> 1409
gcuucaugcc cuucuacaun 20
<210> 1410
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1410
auguagaagg gcaugaagcu u 21
<210> 1411
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 1411
gcuucaugcc cuucuacauu un 22
<210> 1412
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1412
auguagaagg gcaugaagcu u 21
<210> 1413
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1413
gcuucaugcc cuucuacauu u 21
<210> 1414
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1414
auguagaagg gcaugaagcu u 21
<210> 1415
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1415
gcuucaugcc cuucuacauu u 21
<210> 1416
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1416
auguagaagg gcaugaagcu u 21
<210> 1417
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1417
gcuucaugcc cuucuacauu u 21
<210> 1418
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1418
auguagaagg gcaugaagcu u 21
<210> 1419
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1419
gcuucaugcc cuucuacauu u 21
<210> 1420
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1420
auguagaagg gcaugaagcu u 21
<210> 1421
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1421
gcuucaugcc cuucuacauu u 21
<210> 1422
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1422
auguagaagg gcaugaagcu u 21
<210> 1423
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1423
gcuucaugcc cuucuacauu u 21
<210> 1424
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1424
auguagaagg gcaugaagcu u 21
<210> 1425
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1425
gcuucaugcc cuucuacauu u 21
<210> 1426
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1426
auguagaagg gcaugaagcu u 21
<210> 1427
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1427
gcuucaugcc cuucuacauu u 21
<210> 1428
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1428
auguagaagg gcaugaagcu u 21
<210> 1429
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1429
gcuucaugcc cuucuacauu u 21
<210> 1430
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1430
auguagaagg gcaugaagcu u 21
<210> 1431
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 1431
guauguuccu gcuucaugcu un 22
<210> 1432
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1432
gcaugaagca ggaacauacu u 21
<210> 1433
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1433
gguauguucc ugcuucauuu u 21
<210> 1434
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1434
aaugaagcag gaacauaccu u 21
<210> 1435
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1435
guauguuccu gcuucauguu u 21
<210> 1436
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1436
acaugaagca ggaacauacu u 21
<210> 1437
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1437
cggccaaugu ccaccagcuu u 21
<210> 1438
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1438
agcuggugga cauuggccgu u 21
<210> 1439
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1439
uggagcagac ucugcagguu u 21
<210> 1440
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1440
accugcagag ucugcuccau u 21
<210> 1441
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1441
acguacccuu cauugauguu u 21
<210> 1442
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1442
acaucaauga aggguacguu u 21
<210> 1443
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1443
ccagagacug gugacauguu u 21
<210> 1444
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1444
acaugucacc agucucuggu u 21
<210> 1445
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1445
ngcuucaugc cuuucuacau uu 22
<210> 1446
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1446
auguagaaag gcaugaagcu u 21
<210> 1447
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1447
ngcuucaugc cuuucuacau uu 22
<210> 1448
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1448
aaauguagaa aggcaugaag cuu 23
<210> 1449
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1449
ngcuucaugc cuuucuacau uu 22
<210> 1450
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1450
aaauguagaa aggcaugaag cuu 23
<210> 1451
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1451
ugcuucaugc cuuucuacau u 21
<210> 1452
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1452
uguagaaagg caugaagcau u 21
<210> 1453
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1453
uauguuccug cuucaugcuu u 21
<210> 1454
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1454
agcaugaagc aggaacauau u 21
<210> 1455
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1455
uuccugcuuc augccuuuuu u 21
<210> 1456
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1456
aaaaggcaug aagcaggaau u 21
<210> 1457
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1457
ucaugccuuu cuacaguguu u 21
<210> 1458
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1458
acacuguaga aaggcaugau u 21
<210> 1459
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1459
caugccuuuc uacagugguu u 21
<210> 1460
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1460
accacuguag aaaggcaugu u 21
<210> 1461
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1461
augccuuucu acaguggcuu u 21
<210> 1462
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1462
agccacugua gaaaggcauu u 21
<210> 1463
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1463
gguauguucc ugcuucauau u 21
<210> 1464
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1464
uaugaagcag gaacauaccu u 21
<210> 1465
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1465
guauguuccu gcuucaugau u 21
<210> 1466
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1466
ucaugaagca ggaacauacu u 21
<210> 1467
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1467
uauguuccug cuucaugcau u 21
<210> 1468
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1468
ugcaugaagc aggaacauau u 21
<210> 1469
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1469
uuccugcuuc augccuuuau u 21
<210> 1470
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1470
uaaaggcaug aagcaggaau u 21
<210> 1471
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1471
cugcuucaug ccuuucuaau u 21
<210> 1472
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1472
uuagaaaggc augaagcagu u 21
<210> 1473
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1473
gcuucaugcc uuucuacaau u 21
<210> 1474
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1474
uuguagaaag gcaugaagcu u 21
<210> 1475
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1475
uucaugccuu ucuacaguau u 21
<210> 1476
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1476
uacuguagaa aggcaugaau u 21
<210> 1477
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1477
ucaugccuuu cuacagugau u 21
<210> 1478
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1478
ucacuguaga aaggcaugau u 21
<210> 1479
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1479
caugccuuuc uacaguggau u 21
<210> 1480
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1480
uccacuguag aaaggcaugu u 21
<210> 1481
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1481
augccuuucu acaguggcau u 21
<210> 1482
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1482
ugccacugua gaaaggcauu u 21
<210> 1483
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1483
acguacccuu cauugaugau u 21
<210> 1484
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1484
ucaucaauga aggguacguu u 21
<210> 1485
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1485
ccagagacug gugacaugau u 21
<210> 1486
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1486
ucaugucacc agucucuggu u 21
<210> 1487
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1487
auggcuucca gauaugccau u 21
<210> 1488
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1488
uggcauaucu ggaagccauu u 21
<210> 1489
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1489
guuccugcuu caugccuuuu u 21
<210> 1490
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1490
aaaggcauga agcaggaacu u 21
<210> 1491
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1491
ccugcuucau gccuuucuau u 21
<210> 1492
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1492
uagaaaggca ugaagcaggu u 21
<210> 1493
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1493
gcuucaugcc uuucuacauu u 21
<210> 1494
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1494
auguagaaag gcaugaagcu u 21
<210> 1495
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1495
cuucaugccu uucuacaguu u 21
<210> 1496
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1496
acuguagaaa ggcaugaagu u 21
<210> 1497
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1497
uucaugccuu ucuacaguuu u 21
<210> 1498
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1498
aacuguagaa aggcaugaau u 21
<210> 1499
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1499
gcuucauccc uuucuacauu u 21
<210> 1500
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1500
auguagaaag ggaugaagcu u 21
<210> 1501
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1501
ngcuucaugc ccuucuacau uu 22
<210> 1502
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1502
auguagaagg gcaugaagcu u 21
<210> 1503
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1503
ngcuucaugc ccuucuacau uu 22
<210> 1504
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1504
aaauguagaa gggcaugaag cuu 23
<210> 1505
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1505
ngcuucaugc ccuucuacau uu 22
<210> 1506
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1506
aaauguagaa gggcaugaag cuu 23
<210> 1507
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1507
ngcggcuucc ugggcuucua uu 22
<210> 1508
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1508
uagaagccca ggaagccgcu u 21
<210> 1509
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1509
ncugcggcuu ccugggcuuc ua 22
<210> 1510
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1510
uagaagccca ggaagccgca guu 23
<210> 1511
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1511
cugcggcuuc cugggcuucu n 21
<210> 1512
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1512
uagaagccca ggaagccgca guu 23
<210> 1513
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1513
ncugcggcuu ccugggcuuc ua 22
<210> 1514
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1514
uagaagccca ggaagccgca guu 23
<210> 1515
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1515
ngcggcuucc ugggcuucua uu 22
<210> 1516
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1516
uagaagccca ggaagccgcu u 21
<210> 1517
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1517
cugcggcuuc cugggcuucu n 21
<210> 1518
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1518
uagaagccca ggaagccgca guu 23
<210> 1519
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1519
ncugcggcuu ccugggcuuc ua 22
<210> 1520
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1520
uagaagccca ggaagccgca guu 23
<210> 1521
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1521
ngcggcuucc ugggcuucua uu 22
<210> 1522
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1522
uagaagccca ggaagccgcu u 21
<210> 1523
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1523
cugcggcuuc cugggcuucu n 21
<210> 1524
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1524
uagaagccca ggaagccgca guu 23
<210> 1525
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1525
ncugcggcuu ccugggcuuc ua 22
<210> 1526
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1526
uagaagccca ggaagccgca guu 23
<210> 1527
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1527
ngcggcuucc ugggcuucua uu 22
<210> 1528
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1528
uagaagccca ggaagccgcu u 21
<210> 1529
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1529
ncugcggcuu ccugggcuuc ua 22
<210> 1530
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1530
uagaagccca ggaagccgca guu 23
<210> 1531
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1531
ncugcggcuu ccugggcuuc ua 22
<210> 1532
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1532
uagaagccca ggaagccgca guu 23
<210> 1533
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1533
ncugcggcuu ccugggcuuc ua 22
<210> 1534
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1534
uagaagccca ggaagccgca guu 23
<210> 1535
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1535
nauggcuucc agauaugccu uu 22
<210> 1536
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1536
aggcauaucu ggaagccauu u 21
<210> 1537
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1537
nacauggcuu ccagauaugc cu 22
<210> 1538
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1538
aggcauaucu ggaagccaug uuu 23
<210> 1539
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1539
acauggcuuc cagauaugcc n 21
<210> 1540
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1540
aggcauaucu ggaagccaug uuu 23
<210> 1541
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1541
nacauggcuu ccagauaugc cu 22
<210> 1542
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1542
aggcauaucu ggaagccaug uuu 23
<210> 1543
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1543
nauggcuucc agauaugccu uu 22
<210> 1544
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1544
aggcauaucu ggaagccauu u 21
<210> 1545
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1545
acauggcuuc cagauaugcc n 21
<210> 1546
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1546
aggcauaucu ggaagccaug uuu 23
<210> 1547
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1547
nacauggcuu ccagauaugc cu 22
<210> 1548
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1548
aggcauaucu ggaagccaug uuu 23
<210> 1549
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1549
nauggcuucc agauaugccu uu 22
<210> 1550
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1550
aggcauaucu ggaagccauu u 21
<210> 1551
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1551
acauggcuuc cagauaugcc n 21
<210> 1552
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1552
aggcauaucu ggaagccaug uuu 23
<210> 1553
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1553
nacauggcuu ccagauaugc cu 22
<210> 1554
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1554
aggcauaucu ggaagccaug uuu 23
<210> 1555
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1555
nauggcuucc agauaugccu uu 22
<210> 1556
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1556
aggcauaucu ggaagccauu u 21
<210> 1557
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1557
acauggcuuc cagauaugcc n 21
<210> 1558
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1558
aggcauaucu ggaagccaug uuu 23
<210> 1559
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1559
nacauggcuu ccagauaugc cu 22
<210> 1560
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1560
aggcauaucu ggaagccaug uuu 23
<210> 1561
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1561
nacauggcuu ccagauaugc cu 22
<210> 1562
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1562
aggcauaucu ggaagccaug uuu 23
<210> 1563
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1563
nacauggcuu ccagauaugc cu 22
<210> 1564
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1564
aggcauaucu ggaagccaug uuu 23
<210> 1565
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1565
nacauggcuu ccagauaugc cu 22
<210> 1566
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1566
aggcauaucu ggaagccaug uuu 23
<210> 1567
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1567
nacguacccu ucauugaugu uu 22
<210> 1568
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1568
acaucaauga aggguacguu u 21
<210> 1569
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1569
ncaacguacc cuucauugau gu 22
<210> 1570
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1570
acaucaauga aggguacguu guu 23
<210> 1571
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1571
ncaacguacc cuucauugau gu 22
<210> 1572
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1572
acaucaauga aggguacguu guu 23
<210> 1573
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1573
nacguacccu ucauugaugu uu 22
<210> 1574
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1574
acaucaauga aggguacguu u 21
<210> 1575
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1575
caacguaccc uucauugaug n 21
<210> 1576
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1576
acaucaauga aggguacguu guu 23
<210> 1577
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1577
nacguacccu ucauugaugu uu 22
<210> 1578
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1578
acaucaauga aggguacguu u 21
<210> 1579
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1579
caacguaccc uucauugaug n 21
<210> 1580
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1580
acaucaauga aggguacguu guu 23
<210> 1581
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1581
ncaacguacc cuucauugau gu 22
<210> 1582
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1582
acaucaauga aggguacguu guu 23
<210> 1583
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1583
nacguacccu ucauugaugu uu 22
<210> 1584
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1584
acaucaauga aggguacguu u 21
<210> 1585
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1585
caacguaccc uucauugaug n 21
<210> 1586
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1586
acaucaauga aggguacguu guu 23
<210> 1587
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1587
ncaacguacc cuucauugau gu 22
<210> 1588
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1588
acaucaauga aggguacguu guu 23
<210> 1589
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1589
ncaacguacc cuucauugau gu 22
<210> 1590
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1590
acaucaauga aggguacguu guu 23
<210> 1591
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1591
ncaacguacc cuucauugau gu 22
<210> 1592
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1592
acaucaauga aggguacguu guu 23
<210> 1593
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1593
ncaacguacc cuucauugau gu 22
<210> 1594
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1594
acaucaauga aggguacguu guu 23
<210> 1595
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1595
cugcuucaug ccuuucuaca u 21
<210> 1596
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1596
auguagaaag gcaugaagca guu 23
<210> 1597
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1597
cugcuucaug ccuuucuaca u 21
<210> 1598
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1598
auguagaaag gcaugaagca guu 23
<210> 1599
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1599
ngcuucaugc cuuucuacau uu 22
<210> 1600
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1600
auguagaaag gcaugaagcu u 21
<210> 1601
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1601
ngcuucaugc cuuucuacau uu 22
<210> 1602
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1602
auguagaaag gcaugaagcu u 21
<210> 1603
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1603
cugcuucaug ccuuucuaca u 21
<210> 1604
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1604
auguagaaag gcaugaagca guu 23
<210> 1605
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1605
cugcuucaug ccuuucuaca u 21
<210> 1606
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1606
auguagaaag gcaugaagca guu 23
<210> 1607
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1607
ncugcuucau gccuuucuac au 22
<210> 1608
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1608
auguagaaag gcaugaagca guu 23
<210> 1609
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1609
cugcuucaug ccuuucuaca n 21
<210> 1610
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1610
auguagaaag gcaugaagca guu 23
<210> 1611
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1611
ncugcuucau gccuuucuac au 22
<210> 1612
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1612
auguagaaag gcaugaagca guu 23
<210> 1613
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1613
ncugcuucau gccuuucuac au 22
<210> 1614
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1614
auguagaaag gcaugaagca guu 23
<210> 1615
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1615
cugcuucaug ccuuucuaca u 21
<210> 1616
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1616
auguagaaag gcaugaagca guu 23
<210> 1617
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1617
ncugcuucau gccuuucuac au 22
<210> 1618
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1618
auguagaaag gcaugaagca guu 23
<210> 1619
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1619
cugcuucaug ccuuucuaca u 21
<210> 1620
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1620
auguagaaag gcaugaagca guu 23
<210> 1621
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1621
cugcuucaug ccuuucuaca n 21
<210> 1622
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1622
auguagaaag gcaugaagca guu 23
<210> 1623
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1623
ncugcuucau gccuuucuac au 22
<210> 1624
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1624
auguagaaag gcaugaagca guu 23
<210> 1625
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1625
cugcuucaug ccuuucuaca u 21
<210> 1626
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1626
auguagaaag gcaugaagca guu 23
<210> 1627
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1627
cugcuucaug ccuuucuaca n 21
<210> 1628
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1628
auguagaaag gcaugaagca guu 23
<210> 1629
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1629
ncugcuucau gccuuucuac au 22
<210> 1630
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1630
auguagaaag gcaugaagca guu 23
<210> 1631
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1631
cugcuucaug ccuuucuaca n 21
<210> 1632
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1632
auguagaaag gcaugaagca guu 23
<210> 1633
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1633
ncugcuucau gccuuucuac au 22
<210> 1634
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1634
auguagaaag gcaugaagca guu 23
<210> 1635
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1635
ngcuucaugc cuuucuacau uu 22
<210> 1636
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1636
auguagaaag gcaugaagcu u 21
<210> 1637
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1637
ngcuucaugc cuuucuacau uu 22
<210> 1638
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1638
auguagaaag gcaugaagcu u 21
<210> 1639
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1639
ngcuucaugc cuuucuacau uu 22
<210> 1640
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1640
auguagaaag gcaugaagcu u 21
<210> 1641
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1641
ngcuucaugc cuuucuacau uu 22
<210> 1642
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1642
auguagaaag gcaugaagcu u 21
<210> 1643
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1643
ngcuucaugc cuuucuacau uu 22
<210> 1644
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1644
auguagaaag gcaugaagcu u 21
<210> 1645
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1645
cugcuucaug cccuucuaca u 21
<210> 1646
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1646
auguagaagg gcaugaagca guu 23
<210> 1647
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1647
ngcuucaugc ccuucuacau uu 22
<210> 1648
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1648
auguagaagg gcaugaagcu u 21
<210> 1649
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1649
ngcuucaugc ccuucuacau uu 22
<210> 1650
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1650
auguagaagg gcaugaagcu u 21
<210> 1651
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1651
ngcuucaugc ccuucuacau uu 22
<210> 1652
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1652
auguagaagg gcaugaagcu u 21
<210> 1653
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1653
cugcuucaug cccuucuaca n 21
<210> 1654
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1654
auguagaagg gcaugaagca guu 23
<210> 1655
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1655
ncugcuucau gcccuucuac au 22
<210> 1656
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1656
auguagaagg gcaugaagca guu 23
<210> 1657
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1657
ngcuucaugc ccuucuacau uu 22
<210> 1658
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1658
auguagaagg gcaugaagcu u 21
<210> 1659
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1659
auguuccugc uucaugccuu u 21
<210> 1660
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1660
aggcaugaag caggaacauu u 21
<210> 1661
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1661
uguuccugcu ucaugccuuu u 21
<210> 1662
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1662
aaggcaugaa gcaggaacau u 21
<210> 1663
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1663
ugccuuucua caguggccuu u 21
<210> 1664
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1664
aggccacugu agaaaggcau u 21
<210> 1665
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1665
cguacuucgu ccuuguaugu u 21
<210> 1666
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1666
cauacaagga cgaaguacgu u 21
<210> 1667
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1667
ngcuucaugc ccuucuacau uu 22
<210> 1668
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1668
auguagaagg gcaugaagcu u 21
<210> 1669
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1669
ngcuucaugc ccuucuacau uu 22
<210> 1670
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1670
auguagaagg gcaugaagcu u 21
<210> 1671
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1671
ngcuucaugc ccuucuacau uu 22
<210> 1672
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1672
auguagaagg gcaugaagcu u 21
<210> 1673
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1673
ngcuucaugc ccuucuacau uu 22
<210> 1674
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1674
auguagaagg gcaugaagcu u 21
<210> 1675
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1675
ngcuucaugc ccuucuacau uu 22
<210> 1676
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1676
auguagaagg gcaugaagcu u 21
<210> 1677
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1677
ngcuucaugc ccuucuacau uu 22
<210> 1678
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1678
auguagaagg gcaugaagcu u 21
<210> 1679
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1679
nccugcuuca ugccuuucua uu 22
<210> 1680
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1680
uagaaaggca ugaagcaggu u 21
<210> 1681
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1681
nccugcuuca ugccuuucua uu 22
<210> 1682
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1682
uagaaaggca ugaagcaggu u 21
<210> 1683
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1683
uuccugcuuc augccuuucu n 21
<210> 1684
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1684
uagaaaggca ugaagcagga auu 23
<210> 1685
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1685
nccugcuuca ugccuuucua uu 22
<210> 1686
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1686
uagaaaggca ugaagcaggu u 21
<210> 1687
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1687
uuccugcuuc augccuuucu n 21
<210> 1688
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1688
uagaaaggca ugaagcagga auu 23
<210> 1689
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1689
naugccuuuc uacaguggcu uu 22
<210> 1690
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1690
agccacugua gaaaggcauu u 21
<210> 1691
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1691
naugccuuuc uacaguggcu uu 22
<210> 1692
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1692
agccacugua gaaaggcauu u 21
<210> 1693
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1693
naugccuuuc uacaguggcu uu 22
<210> 1694
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1694
agccacugua gaaaggcauu u 21
<210> 1695
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1695
ucaugccuuu cuacaguggc n 21
<210> 1696
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1696
agccacugua gaaaggcaug auu 23
<210> 1697
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1697
naugccuuuc uacaguggcu uu 22
<210> 1698
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1698
agccacugua gaaaggcauu u 21
<210> 1699
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1699
nucaugccuu ucuacagugg cu 22
<210> 1700
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1700
agccacugua gaaaggcaug auu 23
<210> 1701
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1701
nugcuucaug ccuuucuaca gu 22
<210> 1702
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1702
acuguagaaa ggcaugaagc auu 23
<210> 1703
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1703
ncuucaugcc uuucuacagu uu 22
<210> 1704
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1704
acuguagaaa ggcaugaagu u 21
<210> 1705
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1705
ugcuucaugc cuuucuacag n 21
<210> 1706
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1706
acuguagaaa ggcaugaagc auu 23
<210> 1707
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1707
ncuucaugcc uuucuacagu uu 22
<210> 1708
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1708
acuguagaaa ggcaugaagu u 21
<210> 1709
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1709
ugcuucaugc cuuucuacag n 21
<210> 1710
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1710
acuguagaaa ggcaugaagc auu 23
<210> 1711
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1711
nugcuucaug ccuuucuaca gu 22
<210> 1712
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1712
acuguagaaa ggcaugaagc auu 23
<210> 1713
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1713
nugcuucaug ccuuucuaca gu 22
<210> 1714
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1714
acuguagaaa ggcaugaagc auu 23
<210> 1715
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1715
nugcuucaug ccuuucuaca gu 22
<210> 1716
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1716
acuguagaaa ggcaugaagc auu 23
<210> 1717
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1717
nugcuucaug ccuuucuaca gu 22
<210> 1718
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1718
acuguagaaa ggcaugaagc auu 23
<210> 1719
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1719
nguuccugcu ucaugccuuu uu 22
<210> 1720
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1720
aaaggcauga agcaggaacu u 21
<210> 1721
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1721
nccugcuuca ugccuuucua uu 22
<210> 1722
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1722
uagaaaggca ugaagcaggu u 21
<210> 1723
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1723
ncuucaugcc uuucuacagu uu 22
<210> 1724
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1724
acuguagaaa ggcaugaagu u 21
<210> 1725
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1725
nuuccugcuu caugccuuuc ua 22
<210> 1726
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1726
uagaaaggca ugaagcagga auu 23
<210> 1727
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1727
uuccugcuuc augccuuucu n 21
<210> 1728
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1728
uagaaaggca ugaagcagga auu 23
<210> 1729
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1729
nuuccugcuu caugccuuuc ua 22
<210> 1730
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1730
uagaaaggca ugaagcagga auu 23
<210> 1731
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1731
uuccugcuuc augccuuucu n 21
<210> 1732
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1732
uagaaaggca ugaagcagga auu 23
<210> 1733
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1733
nuuccugcuu caugccuuuc ua 22
<210> 1734
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1734
uagaaaggca ugaagcagga auu 23
<210> 1735
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1735
nuuccugcuu caugccuuuc ua 22
<210> 1736
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1736
uagaaaggca ugaagcagga auu 23
<210> 1737
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1737
nuuccugcuu caugccuuuc ua 22
<210> 1738
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1738
uagaaaggca ugaagcagga auu 23
<210> 1739
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1739
nuuccugcuu caugccuuuc ua 22
<210> 1740
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1740
uagaaaggca ugaagcagga auu 23
<210> 1741
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1741
nuuccugcuu caugccuuuc ua 22
<210> 1742
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1742
uagaaaggca ugaagcagga auu 23
<210> 1743
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1743
nuuccugcuu caugccuuuc ua 22
<210> 1744
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1744
uagaaaggca ugaagcagga auu 23
<210> 1745
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1745
nucaugccuu ucuacagugg cu 22
<210> 1746
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1746
agccacugua gaaaggcaug auu 23
<210> 1747
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1747
ucaugccuuu cuacaguggc n 21
<210> 1748
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1748
agccacugua gaaaggcaug auu 23
<210> 1749
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1749
nucaugccuu ucuacagugg cu 22
<210> 1750
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1750
agccacugua gaaaggcaug auu 23
<210> 1751
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1751
ucaugccuuu cuacaguggc n 21
<210> 1752
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1752
agccacugua gaaaggcaug auu 23
<210> 1753
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1753
nucaugccuu ucuacagugg cu 22
<210> 1754
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1754
agccacugua gaaaggcaug auu 23
<210> 1755
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1755
nucaugccuu ucuacagugg cu 22
<210> 1756
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1756
agccacugua gaaaggcaug auu 23
<210> 1757
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1757
ucaugccuuu cuacaguggc n 21
<210> 1758
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1758
agccacugua gaaaggcaug auu 23
<210> 1759
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1759
nucaugccuu ucuacagugg cu 22
<210> 1760
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1760
agccacugua gaaaggcaug auu 23
<210> 1761
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1761
nucaugccuu ucuacagugg cu 22
<210> 1762
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1762
agccacugua gaaaggcaug auu 23
<210> 1763
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1763
nucaugccuu ucuacagugg cu 22
<210> 1764
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1764
agccacugua gaaaggcaug auu 23
<210> 1765
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1765
nugcuucaug ccuuucuaca gu 22
<210> 1766
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1766
acuguagaaa ggcaugaagc auu 23
<210> 1767
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1767
ugcuucaugc cuuucuacag n 21
<210> 1768
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1768
acuguagaaa ggcaugaagc auu 23
<210> 1769
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1769
ugcuucaugc cuuucuacag n 21
<210> 1770
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1770
acuguagaaa ggcaugaagc auu 23
<210> 1771
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1771
nugcuucaug ccuuucuaca gu 22
<210> 1772
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1772
acuguagaaa ggcaugaagc auu 23
<210> 1773
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1773
ncuucaugcc uuucuacagu uu 22
<210> 1774
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1774
acuguagaaa ggcaugaagu u 21
<210> 1775
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1775
nugcuucaug ccuuucuaca gu 22
<210> 1776
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1776
acuguagaaa ggcaugaagc auu 23
<210> 1777
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1777
ngcuucaugc cuuucuacau uu 22
<210> 1778
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1778
auguagaaag gcaugaagcu u 21
<210> 1779
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1779
ncaugccuuu cuacaguggu uu 22
<210> 1780
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1780
accacuguag aaaggcaugu u 21
<210> 1781
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1781
ncugcuucau gccuuucuaa uu 22
<210> 1782
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1782
uuagaaaggc augaagcagu u 21
<210> 1783
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1783
ngcuucaugc cuuucuacaa uu 22
<210> 1784
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1784
uuguagaaag gcaugaagcu u 21
<210> 1785
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1785
nuucaugccu uucuacagua uu 22
<210> 1786
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1786
uacuguagaa aggcaugaau u 21
<210> 1787
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1787
nguuccugcu ucaugccuuu uu 22
<210> 1788
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1788
aaaggcauga agcaggaacu u 21
<210> 1789
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1789
auguuccugc uucaugccuu n 21
<210> 1790
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1790
aaaggcauga agcaggaaca uuu 23
<210> 1791
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1791
nauguuccug cuucaugccu uu 22
<210> 1792
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1792
aaaggcauga agcaggaaca uuu 23
<210> 1793
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1793
nguuccugcu ucaugccuuu uu 22
<210> 1794
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1794
aaaggcauga agcaggaacu u 21
<210> 1795
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1795
auguuccugc uucaugccuu n 21
<210> 1796
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1796
aaaggcauga agcaggaaca uuu 23
<210> 1797
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1797
nauguuccug cuucaugccu uu 22
<210> 1798
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1798
aaaggcauga agcaggaaca uuu 23
<210> 1799
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1799
nguuccugcu ucaugccuuu uu 22
<210> 1800
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1800
aaaggcauga agcaggaacu u 21
<210> 1801
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1801
auguuccugc uucaugccuu n 21
<210> 1802
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1802
aaaggcauga agcaggaaca uuu 23
<210> 1803
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1803
nauguuccug cuucaugccu uu 22
<210> 1804
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1804
aaaggcauga agcaggaaca uuu 23
<210> 1805
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1805
nauguuccug cuucaugccu uu 22
<210> 1806
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1806
aaaggcauga agcaggaaca uuu 23
<210> 1807
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1807
nauguuccug cuucaugccu uu 22
<210> 1808
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1808
aaaggcauga agcaggaaca uuu 23
<210> 1809
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1809
ngcuucaugc cuuucuacag ua 22
<210> 1810
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1810
uacuguagaa aggcaugaag cuu 23
<210> 1811
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1811
ngcuucaugc cuuucuacag ua 22
<210> 1812
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1812
uacuguagaa aggcaugaag cuu 23
<210> 1813
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1813
nuucaugccu uucuacagua uu 22
<210> 1814
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1814
uacuguagaa aggcaugaau u 21
<210> 1815
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1815
ngcuucaugc cuuucuacag ua 22
<210> 1816
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1816
uacuguagaa aggcaugaag cuu 23
<210> 1817
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1817
gcuucaugcc uuucuacagu n 21
<210> 1818
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1818
uacuguagaa aggcaugaag cuu 23
<210> 1819
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1819
ngcggcuucc ugggcuucua uu 22
<210> 1820
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1820
uagaagccca ggaagccgcu u 21
<210> 1821
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1821
nauggcuucc agauaugccu uu 22
<210> 1822
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1822
aggcauaucu ggaagccauu u 21
<210> 1823
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1823
nacauggcuu ccagauaugc cu 22
<210> 1824
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1824
aggcauaucu ggaagccaug uuu 23
<210> 1825
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1825
nacauggcuu ccagauaugc cu 22
<210> 1826
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1826
aggcauaucu ggaagccaug uuu 23
<210> 1827
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1827
ncaacguacc cuucauugau gu 22
<210> 1828
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1828
acaucaauga aggguacguu guu 23
<210> 1829
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1829
ncaacguacc cuucauugau gu 22
<210> 1830
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1830
acaucaauga aggguacguu guu 23
<210> 1831
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1831
nacguacccu ucauugaugu uu 22
<210> 1832
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1832
acaucaauga aggguacguu u 21
<210> 1833
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1833
cugcuucaug ccuuucuaca n 21
<210> 1834
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1834
auguagaaag gcaugaagca guu 23
<210> 1835
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1835
ncugcuucau gccuuucuac au 22
<210> 1836
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1836
auguagaaag gcaugaagca guu 23
<210> 1837
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1837
ngcuucaugc cuuucuacau uu 22
<210> 1838
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1838
auguagaaag gcaugaagcu u 21
<210> 1839
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1839
cugcuucaug ccuuucuaca n 21
<210> 1840
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1840
auguagaaag gcaugaagca guu 23
<210> 1841
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1841
ncugcuucau gccuuucuac au 22
<210> 1842
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1842
auguagaaag gcaugaagca guu 23
<210> 1843
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1843
cugcuucaug ccuuucuaca n 21
<210> 1844
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1844
auguagaaag gcaugaagca guu 23
<210> 1845
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 1845
ncugcuucau gccuuucuac an 22
<210> 1846
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1846
auguagaaag gcaugaagca guu 23
<210> 1847
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1847
ngcuucaugc cuuucuacau uu 22
<210> 1848
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1848
auguagaaag gcaugaagcu u 21
<210> 1849
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1849
ncuucaugcc uuucuacagu uu 22
<210> 1850
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1850
acuguagaaa ggcaugaagu u 21
<210> 1851
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1851
ugcuucaugc cuuucuacag n 21
<210> 1852
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1852
acuguagaaa ggcaugaagc auu 23
<210> 1853
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1853
ncugcuucau gccuuucuac au 22
<210> 1854
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1854
auguagaaag gcaugaagca guu 23
<210> 1855
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1855
cugcuucaug ccuuucuaca n 21
<210> 1856
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1856
auguagaaag gcaugaagca guu 23
<210> 1857
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1857
cugcuucaug ccuuucuaca n 21
<210> 1858
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1858
auguagaaag gcaugaagca guu 23
<210> 1859
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1859
ncuucauccc uuucuacagu uu 22
<210> 1860
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1860
acuguagaaa gggaugaagu u 21
<210> 1861
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1861
ngcuucaucc cuuucuacau uu 22
<210> 1862
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1862
auguagaaag ggaugaagcu u 21
<210> 1863
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1863
ugcuucaucc cuuucuacag n 21
<210> 1864
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1864
acuguagaaa gggaugaagc auu 23
<210> 1865
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1865
cugcuucauc ccuuucuaca n 21
<210> 1866
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1866
auguagaaag ggaugaagca guu 23
<210> 1867
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1867
nacauugcuc uuucaccuga uu 22
<210> 1868
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1868
ucaggugaaa gagcaauguu u 21
<210> 1869
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1869
cugcuucaug ccuuucuaca n 21
<210> 1870
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1870
auguagaaag gcaugaagca guu 23
<210> 1871
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1871
cugcuucaug ccuuucuaca n 21
<210> 1872
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1872
auguagaaag gcaugaagca guu 23
<210> 1873
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1873
cugcuucaug ccuuucuaca n 21
<210> 1874
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1874
auguagaaag gcaugaagca guu 23
<210> 1875
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1875
cugcuucaug ccuuucuaca n 21
<210> 1876
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1876
auguagaaag gcaugaagca guu 23
<210> 1877
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1877
cugcuucaug ccuuucuaca n 21
<210> 1878
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1878
auguagaaag gcaugaagca guu 23
<210> 1879
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1879
cugcuucaug ccuuucuaca n 21
<210> 1880
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1880
auguagaaag gcaugaagca guu 23
<210> 1881
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1881
cugcuucaug ccuuucuaca n 21
<210> 1882
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1882
auguagaaag gcaugaagca guu 23
<210> 1883
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1883
cugcuucaug ccuuucuaca n 21
<210> 1884
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1884
auguagaaag gcaugaagca guu 23
<210> 1885
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1885
cugcuucaug ccuuucuaca n 21
<210> 1886
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1886
auguagaaag gcaugaagca guu 23
<210> 1887
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1887
cugcuucaug ccuuucuaca n 21
<210> 1888
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1888
auguagaaag gcaugaagca guu 23
<210> 1889
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1889
cugcuucaug ccuuucuaca n 21
<210> 1890
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1890
auguagaaag gcaugaagca guu 23
<210> 1891
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1891
ncuucaugcc tuucuacagu uu 22
<210> 1892
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1892
acuguagaaa ggcaugaagu u 21
<210> 1893
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1893
ncuucaugcc uuucuacagu uu 22
<210> 1894
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1894
acuguagaaa ggcaugaagu u 21
<210> 1895
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1895
ncuucaugcc uuucuacagu uu 22
<210> 1896
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1896
acuguagaaa ggcaugaagu u 21
<210> 1897
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1897
ncuucaugcc uuucuacagu uu 22
<210> 1898
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1898
acuguagaaa ggcaugaagu u 21
<210> 1899
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1899
ncuucaugcc uuucuacagu uu 22
<210> 1900
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1900
acuguagaaa ggcaugaagu u 21
<210> 1901
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1901
ncuucaugcc uuucuacagu uu 22
<210> 1902
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1902
acuguagaaa ggcaugaagu u 21
<210> 1903
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1903
ncuucaugcc utucuacagu uu 22
<210> 1904
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1904
acuguagaaa ggcaugaagu u 21
<210> 1905
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1905
ngcuucaugg gauucuacau uu 22
<210> 1906
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1906
auguagaauc ccaugaagcu u 21
<210> 1907
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1907
ncuucaugcg aaucuacagu uu 22
<210> 1908
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1908
acuguagauu cgcaugaagu u 21
<210> 1909
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1909
cugcuucaug ccuuucuaca n 21
<210> 1910
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1910
uuguagaaag gcaugaagca guu 23
<210> 1911
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1911
ncugcuucau gccuuucuac aa 22
<210> 1912
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1912
uuguagaaag gcaugaagca guu 23
<210> 1913
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1913
cugcuucaug ccuuucuaca a 21
<210> 1914
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1914
uuguagaaag gcaugaagca guu 23
<210> 1915
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1915
cugcuucaug ggauucuaca n 21
<210> 1916
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1916
auguagaauc ccaugaagca guu 23
<210> 1917
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1917
ncugcuucau gggauucuac au 22
<210> 1918
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1918
auguagaauc ccaugaagca guu 23
<210> 1919
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1919
ncuucaugcc uuucuacagu uu 22
<210> 1920
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1920
acuguagaaa ggcaugaagu u 21
<210> 1921
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1921
ncuucaugcc uuucuacagu uu 22
<210> 1922
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1922
acuguagaaa ggcaugaagu u 21
<210> 1923
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1923
ngcuucaugc cuuucuacau uu 22
<210> 1924
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1924
auguagaaag gcaugaagcu u 21
<210> 1925
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 1925
nugcuucaug ccuuucuaca gn 22
<210> 1926
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1926
acuguagaaa ggcaugaagc auu 23
<210> 1927
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1927
ncuucaugcc uuucuacagu uu 22
<210> 1928
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1928
acuguagaaa ggcaugaagu u 21
<210> 1929
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1929
ugcuucaugc cuuucuacag n 21
<210> 1930
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1930
acuguagaaa ggcaugaagc auu 23
<210> 1931
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1931
ugcuucaugc cuuucuacag n 21
<210> 1932
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1932
acuguagaaa ggcaugaagc auu 23
<210> 1933
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1933
ugcuucaugc cuuucuacag n 21
<210> 1934
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1934
acuguagaaa ggcaugaagc auu 23
<210> 1935
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1935
ncuucaugcc uuucuacagu uu 22
<210> 1936
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1936
acuguagaaa ggcaugaagu u 21
<210> 1937
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1937
ugcuucaugc cuuucuacag n 21
<210> 1938
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1938
acuguagaaa ggcaugaagc auu 23
<210> 1939
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1939
augccuuucu acaguggcuu n 21
<210> 1940
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1940
agccacugua gaaaggcaug auu 23
<210> 1941
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1941
ucaugccuuu cuacaguggc n 21
<210> 1942
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1942
agccacugua gaaaggcaug auu 23
<210> 1943
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1943
naugccuuuc uacaguggcu uu 22
<210> 1944
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1944
agccacugua gaaaggcauu u 21
<210> 1945
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1945
naugccuuuc uacaguggcu uu 22
<210> 1946
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1946
agccacugua gaaaggcauu u 21
<210> 1947
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1947
nucaugccuu ucuacagugg cu 22
<210> 1948
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1948
agccacugua gaaaggcaug auu 23
<210> 1949
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1949
ucaugccuuu cuacaguggc n 21
<210> 1950
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1950
agccacugua gaaaggcaug auu 23
<210> 1951
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1951
naugccuuuc uacaguggcu uu 22
<210> 1952
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1952
agccacugua gaaaggcauu u 21
<210> 1953
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1953
ucaugccuuu cuacaguggc n 21
<210> 1954
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1954
agccacugua gaaaggcaug auu 23
<210> 1955
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1955
ucaugccuuu cuacaguggc n 21
<210> 1956
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1956
agccacugua gaaaggcaug auu 23
<210> 1957
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 1957
nucaugccuu ucuacagugg cn 22
<210> 1958
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1958
agccacugua gaaaggcaug auu 23
<210> 1959
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1959
naugccuuuc uacaguggca uu 22
<210> 1960
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1960
ugccacugua gaaaggcauu u 21
<210> 1961
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1961
ucaugccuuu cuacaguggc n 21
<210> 1962
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1962
ugccacugua gaaaggcaug auu 23
<210> 1963
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1963
nucaugccuu ucuacagugg ca 22
<210> 1964
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1964
ugccacugua gaaaggcaug auu 23
<210> 1965
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1965
ucaugccuuu cuacaguggc a 21
<210> 1966
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1966
ugccacugua gaaaggcaug auu 23
<210> 1967
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1967
cugcuucaug ccuuucuaca n 21
<210> 1968
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1968
auguagaaag gcaugaagca guu 23
<210> 1969
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1969
cugcuucaug ccuuucuaca n 21
<210> 1970
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1970
uuguagaaag gcaugaagca guu 23
<210> 1971
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1971
cugcuucaug ccuuucuaca a 21
<210> 1972
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1972
uuguagaaag gcaugaagca guu 23
<210> 1973
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1973
ucaugccuuu cuacaguggc n 21
<210> 1974
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1974
ugccacugua gaaaggcaug auu 23
<210> 1975
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 1975
ucaugccuuu cuacaguggc a 21
<210> 1976
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1976
ugccacugua gaaaggcaug auu 23
<210> 1977
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 1977
ncuucaugcc uuucuacagu uu 22
<210> 1978
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1978
acuguagaaa ggcaugaagu u 21
<210> 1979
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1979
cugcuucaug ccuuucuaca n 21
<210> 1980
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1980
auguanaaag gcaugaagca guu 23
<210> 1981
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1981
cugcuucaug ccuuucuaca n 21
<210> 1982
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1982
auguanaaag gcaugaagca guu 23
<210> 1983
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1983
ugcuucaugc cuuucuacag n 21
<210> 1984
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1984
acugungaaa ggcaugaagc auu 23
<210> 1985
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1985
ugcuucaugc cuuucuacag n 21
<210> 1986
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1986
acugungaaa ggcaugaagc auu 23
<210> 1987
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1987
ucaugccuuu cuacaguggc n 21
<210> 1988
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1988
agccanugua gaaaggcaug auu 23
<210> 1989
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1989
ucaugccuuu cuacaguggc n 21
<210> 1990
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 1990
agccanugua gaaaggcaug auu 23
<210> 1991
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1991
cugcuucaug ccuuucuaca n 21
<210> 1992
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1992
auguagaaag gcaugaagca guu 23
<210> 1993
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1993
cugcuucaug ccuuucuaca n 21
<210> 1994
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1994
auguagaaag gcaugaagca guu 23
<210> 1995
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1995
cugcuucaug ccuuucuaca n 21
<210> 1996
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1996
auguagaaag gcaugaagca guu 23
<210> 1997
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1997
cugcuucaug ccuuucuaca n 21
<210> 1998
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 1998
auguagaaag gcaugaagca guu 23
<210> 1999
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 1999
cugcuucaug ccuuucuaca n 21
<210> 2000
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2000
auguagaaag gcaugaagca guu 23
<210> 2001
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2001
cugcuucaug ccuuucuaca n 21
<210> 2002
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2002
auguagaaag gcaugaagca guu 23
<210> 2003
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2003
cugcuucaug ccuuucuaca n 21
<210> 2004
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2004
auguagaaag gcaugaagca guu 23
<210> 2005
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 2005
ncugcuucau gccuuucuac au 22
<210> 2006
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2006
auguagaaag gcaugaagca guu 23
<210> 2007
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 2007
ncugcuucau gccuuucuac an 22
<210> 2008
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2008
auguagaaag gcaugaagca guu 23
<210> 2009
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2009
cugcuucaug ccuuucuaca n 21
<210> 2010
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2010
auguagaaag gcaugaagca guu 23
<210> 2011
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2011
cugcuucaug ccuuucuaca n 21
<210> 2012
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2012
auguagaaag gcaugaagca guu 23
<210> 2013
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 2013
ncugcuucau gccuuucuac au 22
<210> 2014
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2014
auguagaaag gcaugaagca guu 23
<210> 2015
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2015
cugcuucaug ccuuucuaca n 21
<210> 2016
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2016
auguagaaag gcaugaagca guu 23
<210> 2017
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2017
cugcuucaug ccuuucuaca n 21
<210> 2018
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2018
auguagaaag gcaugaagca guu 23
<210> 2019
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 2019
ncugcuucau gccuuucuac au 22
<210> 2020
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2020
auguagaaag gcaugaagca guu 23
<210> 2021
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 2021
ncugcuucau gccuuucuac an 22
<210> 2022
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2022
auguagaaag gcaugaagca guu 23
<210> 2023
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2023
cugcuucaug ccuuucuaca n 21
<210> 2024
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (2)..(2)
<223> Abasic nucleotide
<400> 2024
anguagaaag gcaugaagca guu 23
<210> 2025
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2025
cugcuucaug ccuuucuaca n 21
<210> 2026
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (3)..(3)
<223> Abasic nucleotide
<400> 2026
aunuagaaag gcaugaagca guu 23
<210> 2027
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2027
cugcuucaug ccuuucuaca n 21
<210> 2028
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (4)..(4)
<223> Abasic nucleotide
<400> 2028
augnagaaag gcaugaagca guu 23
<210> 2029
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2029
cugcuucaug ccuuucuaca n 21
<210> 2030
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (5)..(5)
<223> Abasic nucleotide
<400> 2030
augungaaag gcaugaagca guu 23
<210> 2031
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2031
cugcuucaug ccuuucuaca n 21
<210> 2032
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (7)..(7)
<223> Abasic nucleotide
<400> 2032
auguagnaag gcaugaagca guu 23
<210> 2033
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2033
cugcuucaug ccuuucuaca n 21
<210> 2034
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (8)..(8)
<223> Abasic nucleotide
<400> 2034
auguaganag gcaugaagca guu 23
<210> 2035
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2035
caacguaccc uucauugaug n 21
<210> 2036
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2036
acaucaauga aggguacguu guu 23
<210> 2037
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2037
caacguaccc uucauugaug n 21
<210> 2038
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2038
acaucaauga aggguacguu guu 23
<210> 2039
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2039
acauggcuuc cagauaugcc n 21
<210> 2040
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2040
aggcauaucu ggaagccaug uuu 23
<210> 2041
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2041
acauggcuuc cagauaugcc n 21
<210> 2042
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2042
aggcauaucu ggaagccaug uuu 23
<210> 2043
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2043
cugcuucaug ccuuucuaca n 21
<210> 2044
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2044
auguagaaag gcaugaagca guu 23
<210> 2045
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2045
cugcuucaug ccuuucuaca n 21
<210> 2046
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2046
auguagaaag gcaugaagca guu 23
<210> 2047
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2047
cugcuucaug ccuuucuaca n 21
<210> 2048
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2048
auguagaaag gcaugaagca guu 23
<210> 2049
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2049
cugcggcuuc cugggcuucu n 21
<210> 2050
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2050
uagaagccca ggaagccgca guu 23
<210> 2051
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2051
cugcggcuuc cugggcuucu n 21
<210> 2052
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2052
uagaagccca ggaagccgca guu 23
<210> 2053
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2053
ugcuucaugc cuuucuacag n 21
<210> 2054
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2054
acuguagaaa ggcaugaagc auu 23
<210> 2055
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<400> 2055
nugcuucaug ccuuucuaca gu 22
<210> 2056
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2056
acuguagaaa ggcaugaagc auu 23
<210> 2057
<211> 22
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (1)..(1)
<223> Inverted abasic nucleotide
<220>
<221> modified_base
<222> (22)..(22)
<223> Inverted abasic nucleotide
<400> 2057
nugcuucaug ccuuucuaca gn 22
<210> 2058
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2058
acuguagaaa ggcaugaagc auu 23
<210> 2059
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2059
ugcuucaugc cuuucuacag n 21
<210> 2060
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2060
acuguagaaa ggcaugaagc auu 23
<210> 2061
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2061
ugcuucaugc cuuucuacag n 21
<210> 2062
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2062
acuguagaaa ggcaugaagc auu 23
<210> 2063
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2063
ugcuucaugc cuuucuacag n 21
<210> 2064
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2064
acuguagaaa ggcaugaagc auu 23
<210> 2065
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2065
cugcuucaug ccuuucuaca u 21
<210> 2066
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2066
auguagaaag gcaugaagca guu 23
<210> 2067
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2067
cugcuucaug ccuuucuaca u 21
<210> 2068
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2068
auguagaaag gcaugaagca guu 23
<210> 2069
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2069
cugcuucaug ccuuucuaca u 21
<210> 2070
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2070
auguagaaag gcaugaagca guu 23
<210> 2071
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2071
ugcuucaugc cuuucuacag n 21
<210> 2072
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2072
ucuguagaaa ggcaugaagc auu 23
<210> 2073
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2073
ugcuucaugc cuuucuacag a 21
<210> 2074
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2074
ucuguagaaa ggcaugaagc auu 23
<210> 2075
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2075
cugcuucaug ccuuucuaca t 21
<210> 2076
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2076
auguagaaag gcaugaagca guu 23
<210> 2077
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2077
cugcuucaug ccuuucuaca n 21
<210> 2078
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2078
auguagaaag gcaugaagca guu 23
<210> 2079
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2079
cugcuucaug ccuuucuaca n 21
<210> 2080
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2080
auguagaaag gcaugaagca guu 23
<210> 2081
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2081
cugcuucaug ccuuucuaca n 21
<210> 2082
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2082
auguagaaag gcaugaagca guu 23
<210> 2083
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2083
cugcuucaug ccuuucuaca n 21
<210> 2084
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2084
auguagaaag gcaugaagca guu 23
<210> 2085
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2085
cugcuucaug ccuuucuaca n 21
<210> 2086
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2086
auguagaaag gcaugaagca guu 23
<210> 2087
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2087
cugcuucaug ccuuucuaca n 21
<210> 2088
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2088
auguagaaag gcaugaagca guu 23
<210> 2089
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2089
cugcuucaug ccuuucuaca n 21
<210> 2090
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2090
auguagaaag gcaugaagca guu 23
<210> 2091
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2091
cugcuucaug ccuuucuaca n 21
<210> 2092
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2092
auguagaaag gcaugaagca guu 23
<210> 2093
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2093
cugcuucaug ccuuucuaca n 21
<210> 2094
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2094
auguagaaag gcaugaagca guu 23
<210> 2095
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2095
cugcuucaug ccuuucuaca n 21
<210> 2096
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2096
auguagaaag gcaugaagca guu 23
<210> 2097
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2097
cugcuucaug ccuuucuaca n 21
<210> 2098
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2098
auguagaaag gcaugaagca guu 23
<210> 2099
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2099
cugcuucaug ccuuucuaca n 21
<210> 2100
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2100
auguagaaag gcaugaagca guu 23
<210> 2101
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2101
cugcuucaug ccuuucuaca n 21
<210> 2102
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2102
auguagaaag gcaugaagca guu 23
<210> 2103
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2103
cugcuucaug ccuuucuaca n 21
<210> 2104
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2104
auguagaaag gcaugaagca guu 23
<210> 2105
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2105
cugcuucaug ccuuucuaca n 21
<210> 2106
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2106
auguagaaag gcaugaagca guu 23
<210> 2107
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2107
cugcuucaug ccuuucuaca n 21
<210> 2108
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2108
auguagaaag gcaugaagca guu 23
<210> 2109
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2109
cugcuucaug ccuuucuaca n 21
<210> 2110
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2110
auguagaaag gcaugaagca guu 23
<210> 2111
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2111
cugcuucaug ccuuucuaca n 21
<210> 2112
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2112
auguagaaag gcaugaagca guu 23
<210> 2113
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2113
cugcuucaug ccuuucuaca n 21
<210> 2114
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2114
auguagaaag gcaugaagca guu 23
<210> 2115
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2115
cugcuucaug ccuuucuaca n 21
<210> 2116
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2116
auguagaaag gcaugaagca guu 23
<210> 2117
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2117
cugcuucaug ccuuucuaca n 21
<210> 2118
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2118
auguagaaag gcaugaagca guu 23
<210> 2119
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2119
cugcuucaug ccuuucuaca n 21
<210> 2120
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2120
auguagaaag gcaugaagca guu 23
<210> 2121
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2121
cugcuucaug ccuuucuaca n 21
<210> 2122
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2122
auguagaaag gcaugaagca guu 23
<210> 2123
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2123
cugcuucaug ccuuucuaca n 21
<210> 2124
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2124
auguagaaag gcaugaagca guu 23
<210> 2125
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2125
cugcuucaug ccuuucuaca n 21
<210> 2126
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2126
auguagaaag gcaugaagca guu 23
<210> 2127
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2127
cugcuucaug ccuuucuaca n 21
<210> 2128
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2128
auguagaaag gcaugaagca guu 23
<210> 2129
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2129
cugcuucaug ccuuucuaca n 21
<210> 2130
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2130
auguagaaag gcaugaagca guu 23
<210> 2131
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2131
ugcuucaugc cuuucuacag a 21
<210> 2132
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2132
ucuguagaaa ggcaugaagc auu 23
<210> 2133
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2133
ugcuucaugc cuuucuacag a 21
<210> 2134
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2134
ucuguagaaa ggcaugaagc auu 23
<210> 2135
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2135
ugcuucaugc cuuucuacag a 21
<210> 2136
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2136
ucuguagaaa ggcaugaagc auu 23
<210> 2137
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2137
ugcuucaugc cuuucuacag a 21
<210> 2138
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2138
ucuguagaaa ggcaugaagc auu 23
<210> 2139
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2139
ugcuucaugc cuuucuacag a 21
<210> 2140
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2140
ucuguagaaa ggcaugaagc auu 23
<210> 2141
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2141
ugcuucaugc cuuucuacag a 21
<210> 2142
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (2)..(2)
<223> Abasic nucleotide
<400> 2142
unuguagaaa ggcaugaagc auu 23
<210> 2143
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2143
ugcuucaugc cuuucuacag a 21
<210> 2144
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (3)..(3)
<223> Abasic nucleotide
<400> 2144
ucnguagaaa ggcaugaagc auu 23
<210> 2145
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2145
ugcuucaugc cuuucuacag a 21
<210> 2146
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (4)..(4)
<223> Abasic nucleotide
<400> 2146
ucunuagaaa ggcaugaagc auu 23
<210> 2147
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2147
ugcuucaugc cuuucuacag a 21
<210> 2148
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (5)..(5)
<223> Abasic nucleotide
<400> 2148
ucugnagaaa ggcaugaagc auu 23
<210> 2149
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2149
ugcuucaugc cuuucuacag a 21
<210> 2150
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 2150
ucugungaaa ggcaugaagc auu 23
<210> 2151
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2151
ugcuucaugc cuuucuacag a 21
<210> 2152
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (7)..(7)
<223> Abasic nucleotide
<400> 2152
ucuguanaaa ggcaugaagc auu 23
<210> 2153
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2153
ugcuucaugc cuuucuacag a 21
<210> 2154
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (8)..(8)
<223> Abasic nucleotide
<400> 2154
ucuguagnaa ggcaugaagc auu 23
<210> 2155
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2155
ucaugccuuu cuacaguggc t 21
<210> 2156
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2156
agccacugua gaaaggcaug auu 23
<210> 2157
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2157
ucaugccuuu cuacaguggc n 21
<210> 2158
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2158
ugccacugua gaaaggcaug auu 23
<210> 2159
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2159
ucaugccuuu cuacaguggc a 21
<210> 2160
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2160
ugccacugua gaaaggcaug auu 23
<210> 2161
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2161
uccugcuuca ugccuuucua t 21
<210> 2162
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2162
auagaaaggc augaagcagg auu 23
<210> 2163
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2163
uccugcuuca ugccuuucua n 21
<210> 2164
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2164
uuagaaaggc augaagcagg auu 23
<210> 2165
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2165
uccugcuuca ugccuuucua a 21
<210> 2166
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2166
uuagaaaggc augaagcagg auu 23
<210> 2167
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2167
uauguuccug cuucaugccu t 21
<210> 2168
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2168
aaggcaugaa gcaggaacau auu 23
<210> 2169
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2169
uauguuccug cuucaugccu n 21
<210> 2170
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2170
uaggcaugaa gcaggaacau auu 23
<210> 2171
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2171
uauguuccug cuucaugccu a 21
<210> 2172
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2172
uaggcaugaa gcaggaacau auu 23
<210> 2173
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2173
uccugcuuca ugccuuucua n 21
<210> 2174
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2174
auagaaaggc augaagcagg auu 23
<210> 2175
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2175
uauguuccug cuucaugccu n 21
<210> 2176
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2176
aaggcaugaa gcaggaacau auu 23
<210> 2177
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2177
ucaugccuuu cuacaguggc t 21
<210> 2178
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2178
agccacugua gaaaggcaug auu 23
<210> 2179
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2179
uccugcuuca ugccuuucua t 21
<210> 2180
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2180
auagaaaggc augaagcagg auu 23
<210> 2181
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2181
uccugcuuca ugccuuucua a 21
<210> 2182
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2182
uuagaaaggc augaagcagg auu 23
<210> 2183
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2183
uauguuccug cuucaugccu a 21
<210> 2184
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2184
uaggcaugaa gcaggaacau auu 23
<210> 2185
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2185
ugcuucaugc cuuucuacag a 21
<210> 2186
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2186
ucuguagaaa ggcaugaagc auu 23
<210> 2187
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2187
cugcuucaug ccuuucuaca n 21
<210> 2188
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2188
auguagaaag gcaugaagca guu 23
<210> 2189
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2189
cugcuucaug ccuuucuaca n 21
<210> 2190
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2190
auguagaaag gcaugaagca guu 23
<210> 2191
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2191
cugcuucaug ccuuucuaca n 21
<210> 2192
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2192
auguagaaag gcaugaagca guu 23
<210> 2193
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2193
cugcuucaug ccuuucuaca n 21
<210> 2194
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2194
auguagaaag gcaugaagca guu 23
<210> 2195
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2195
cugcuucaug ccuuucuaca n 21
<210> 2196
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2196
auguagaaag gcaugaagca guu 23
<210> 2197
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2197
cugcuucaug ccuuucuaca n 21
<210> 2198
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2198
auguagaaag gcaugaagca guu 23
<210> 2199
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2199
cugcuucaug ccuuucuaca n 21
<210> 2200
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2200
auguagaaag gcaugaagca guu 23
<210> 2201
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2201
cugcuucaug ccuuucuaca n 21
<210> 2202
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2202
auguagaaag gcaugaagca guu 23
<210> 2203
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2203
cugcuucaug ccuuucuaca n 21
<210> 2204
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2204
auguagaaag gcaugaagca guu 23
<210> 2205
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2205
cugcuucaug ccutucuaca n 21
<210> 2206
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2206
auguagaaag gcaugaagca guu 23
<210> 2207
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2207
cugcuucaug cctuucuaca n 21
<210> 2208
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2208
auguagaaag gcaugaagca guu 23
<210> 2209
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2209
cugcuucaug ccuutcuaca n 21
<210> 2210
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2210
auguagaaag gcaugaagca guu 23
<210> 2211
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2211
cugcuucaug ccuuuctaca n 21
<210> 2212
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2212
auguagaaag gcaugaagca guu 23
<210> 2213
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2213
cugcuucaug ccuuucuaca n 21
<210> 2214
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2214
auguagaaag gcaugaagca guu 23
<210> 2215
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2215
cugcuucaug ccuuucuaca n 21
<210> 2216
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2216
auguagaaag gcaugaagca guu 23
<210> 2217
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2217
cugcuucaug ccuutcuaca n 21
<210> 2218
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (7)..(7)
<223> Abasic nucleotide
<400> 2218
auguagnaag gcaugaagca guu 23
<210> 2219
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2219
cugcuucaug ccuuuctaca n 21
<210> 2220
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (5)..(5)
<223> Abasic nucleotide
<400> 2220
augungaaag gcaugaagca guu 23
<210> 2221
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2221
cugcuucaug ccuuucuaca n 21
<210> 2222
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (4)..(4)
<223> Abasic nucleotide
<400> 2222
augnagaaag gcaugaagca guu 23
<210> 2223
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2223
cugcuucaug ccuuucuaca n 21
<210> 2224
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2224
auguagaaag gcaugaagca guu 23
<210> 2225
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2225
cugcuucaug ccuuucuaca n 21
<210> 2226
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2226
auguagaaag gcaugaagca guu 23
<210> 2227
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2227
cugcuucaug ccutucuaca n 21
<210> 2228
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2228
auguagaaag gcaugaagca guu 23
<210> 2229
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2229
cugcuucaug ccutucuaca n 21
<210> 2230
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2230
auguagaaag gcaugaagca guu 23
<210> 2231
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2231
cugcuucaug ccutucuaca n 21
<210> 2232
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2232
auguagaaag gcaugaagca guu 23
<210> 2233
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2233
cugcuucaug ccutucuaca n 21
<210> 2234
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2234
auguagaaag gcaugaagca guu 23
<210> 2235
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2235
ugcuucaugc cuuucuacag a 21
<210> 2236
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (5)..(5)
<223> Abasic nucleotide
<400> 2236
ucugnagaaa ggcaugaagc auu 23
<210> 2237
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2237
ugcuucaugc cuuuctacag a 21
<210> 2238
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 2238
ucugungaaa ggcaugaagc auu 23
<210> 2239
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2239
ugcuucaugc cuutcuacag a 21
<210> 2240
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (8)..(8)
<223> Abasic nucleotide
<400> 2240
ucuguagnaa ggcaugaagc auu 23
<210> 2241
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2241
ugcuucaugc cuuucuacag a 21
<210> 2242
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2242
ucuguagaaa ggcaugaagc auu 23
<210> 2243
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2243
ugcuucaugc cuuucuacag a 21
<210> 2244
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2244
ucuguagaaa ggcaugaagc auu 23
<210> 2245
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2245
ugcuucaugc cuuuctacag a 21
<210> 2246
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2246
ucuguagaaa ggcaugaagc auu 23
<210> 2247
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2247
ugcuucaugc cuuucuacag a 21
<210> 2248
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (2)..(2)
<223> Abasic nucleotide
<400> 2248
unuguagaaa ggcaugaagc auu 23
<210> 2249
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<400> 2249
ugcuucaugc cuuucuacag a 21
<210> 2250
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (3)..(3)
<223> Abasic nucleotide
<400> 2250
ucnguagaaa ggcaugaagc auu 23
<210> 2251
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2251
ucaugccuuu cuacaguggc n 21
<210> 2252
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 2252
agccanugua gaaaggcaug auu 23
<210> 2253
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2253
ucaugccuuu cuacagtggc n 21
<210> 2254
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 2254
agccanugua gaaaggcaug auu 23
<210> 2255
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (21)..(21)
<223> Inverted abasic nucleotide
<400> 2255
ucaugccuuu cuacaguggc n 21
<210> 2256
<211> 23
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<220>
<221> modified_base
<222> (6)..(6)
<223> Abasic nucleotide
<400> 2256
agccanugua gaaaggcaug auu 23
<210> 2257
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2257
gguauguucc ugcuucauuu u 21
<210> 2258
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2258
aaugaagcag gaacauaccu u 21
<210> 2259
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2259
gguauguucc ugcuucauau u 21
<210> 2260
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2260
uaugaagcag gaacauaccu u 21
<210> 2261
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2261
guauguuccu gcuucauguu u 21
<210> 2262
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2262
acaugaagca ggaacauacu u 21
<210> 2263
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2263
uauguuccug cuucaugcau u 21
<210> 2264
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2264
ugcaugaagc aggaacauau u 21
<210> 2265
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2265
auguuccugc uucaugccuu u 21
<210> 2266
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2266
aggcaugaag caggaacauu u 21
<210> 2267
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2267
uguuccugcu ucaugccuuu u 21
<210> 2268
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2268
aaggcaugaa gcaggaacau u 21
<210> 2269
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2269
guuccugcuu caugccuuuu u 21
<210> 2270
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2270
aaaggcauga agcaggaacu u 21
<210> 2271
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2271
uuccugcuuc augccuuuuu u 21
<210> 2272
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2272
aaaaggcaug aagcaggaau u 21
<210> 2273
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2273
uuccugcuuc augccuuuau u 21
<210> 2274
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2274
uaaaggcaug aagcaggaau u 21
<210> 2275
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2275
uccugcuuca ugccuuucuu u 21
<210> 2276
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2276
agaaaggcau gaagcaggau u 21
<210> 2277
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2277
ccugcuucau gccuuucuau u 21
<210> 2278
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2278
uagaaaggca ugaagcaggu u 21
<210> 2279
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2279
cugcuucaug ccuuucuauu u 21
<210> 2280
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2280
auagaaaggc augaagcagu u 21
<210> 2281
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2281
cugcuucaug ccuuucuaau u 21
<210> 2282
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2282
uuagaaaggc augaagcagu u 21
<210> 2283
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2283
ugcuucaugc cuuucuacau u 21
<210> 2284
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2284
uguagaaagg caugaagcau u 21
<210> 2285
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2285
gcuucaugcc uuucuacauu u 21
<210> 2286
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2286
auguagaaag gcaugaagcu u 21
<210> 2287
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2287
gcuucaugcc uuucuacaau u 21
<210> 2288
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2288
uuguagaaag gcaugaagcu u 21
<210> 2289
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2289
cuucaugccu uucuacaguu u 21
<210> 2290
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2290
acuguagaaa ggcaugaagu u 21
<210> 2291
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2291
uucaugccuu ucuacaguuu u 21
<210> 2292
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2292
aacuguagaa aggcaugaau u 21
<210> 2293
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2293
uucaugccuu ucuacaguau u 21
<210> 2294
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2294
uacuguagaa aggcaugaau u 21
<210> 2295
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2295
ucaugccuuu cuacaguguu u 21
<210> 2296
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2296
acacuguaga aaggcaugau u 21
<210> 2297
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2297
ucaugccuuu cuacagugau u 21
<210> 2298
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2298
ucacuguaga aaggcaugau u 21
<210> 2299
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2299
caugccuuuc uacagugguu u 21
<210> 2300
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2300
accacuguag aaaggcaugu u 21
<210> 2301
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2301
caugccuuuc uacaguggau u 21
<210> 2302
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2302
uccacuguag aaaggcaugu u 21
<210> 2303
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2303
augccuuucu acaguggcuu u 21
<210> 2304
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2304
agccacugua gaaaggcauu u 21
<210> 2305
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2305
augccuuucu acaguggcau u 21
<210> 2306
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2306
ugccacugua gaaaggcauu u 21
<210> 2307
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2307
ugccuuucua caguggccuu u 21
<210> 2308
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2308
aggccacugu agaaaggcau u 21
<210> 2309
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2309
gccuuucuac aguggccuuu u 21
<210> 2310
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2310
aaggccacug uagaaaggcu u 21
<210> 2311
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2311
gguauguucc ugcuucaucu u 21
<210> 2312
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2312
gaugaagcag gaacauaccu u 21
<210> 2313
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2313
guauguuccu gcuucauccu u 21
<210> 2314
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2314
ggaugaagca ggaacauacu u 21
<210> 2315
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2315
uauguuccug cuucaucccu u 21
<210> 2316
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2316
gggaugaagc aggaacauau u 21
<210> 2317
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2317
auguuccugc uucauccccu u 21
<210> 2318
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2318
ggggaugaag caggaacauu u 21
<210> 2319
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2319
uguuccugcu ucauccccuu u 21
<210> 2320
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2320
aggggaugaa gcaggaacau u 21
<210> 2321
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2321
guuccugcuu cauccccuuu u 21
<210> 2322
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2322
aaggggauga agcaggaacu u 21
<210> 2323
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2323
uuccugcuuc auccccuucu u 21
<210> 2324
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2324
gaaggggaug aagcaggaau u 21
<210> 2325
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2325
uccugcuuca uccccuucuu u 21
<210> 2326
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2326
agaaggggau gaagcaggau u 21
<210> 2327
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2327
ccugcuucau ccccuucuau u 21
<210> 2328
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2328
uagaagggga ugaagcaggu u 21
<210> 2329
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2329
cugcuucauc cccuucuacu u 21
<210> 2330
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2330
guagaagggg augaagcagu u 21
<210> 2331
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2331
ugcuucaucc ccuucuacau u 21
<210> 2332
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2332
uguagaaggg gaugaagcau u 21
<210> 2333
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2333
gcuucauccc cuucuacagu u 21
<210> 2334
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2334
cuguagaagg ggaugaagcu u 21
<210> 2335
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2335
cuucaucccc uucuacaguu u 21
<210> 2336
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2336
acuguagaag gggaugaagu u 21
<210> 2337
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2337
uucauccccu ucuacagugu u 21
<210> 2338
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2338
cacuguagaa ggggaugaau u 21
<210> 2339
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2339
ucauccccuu cuacaguggu u 21
<210> 2340
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2340
ccacuguaga aggggaugau u 21
<210> 2341
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2341
cauccccuuc uacaguggcu u 21
<210> 2342
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2342
gccacuguag aaggggaugu u 21
<210> 2343
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2343
auccccuucu acaguggccu u 21
<210> 2344
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2344
ggccacugua gaaggggauu u 21
<210> 2345
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2345
uccccuucua caguggccuu u 21
<210> 2346
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2346
aggccacugu agaaggggau u 21
<210> 2347
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2347
ccccuucuac aguggccuuu u 21
<210> 2348
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2348
aaggccacug uagaaggggu u 21
<210> 2349
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2349
gguauguucc ugcuucauuu u 21
<210> 2350
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2350
aaugaagcag gaacauaccu u 21
<210> 2351
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2351
gguauguucc ugcuucauau u 21
<210> 2352
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2352
uaugaagcag gaacauaccu u 21
<210> 2353
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2353
guauguuccu gcuucauguu u 21
<210> 2354
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2354
acaugaagca ggaacauacu u 21
<210> 2355
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2355
uauguuccug cuucaugcau u 21
<210> 2356
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2356
ugcaugaagc aggaacauau u 21
<210> 2357
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2357
auguuccugc uucaugccuu u 21
<210> 2358
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2358
aggcaugaag caggaacauu u 21
<210> 2359
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2359
uguuccugcu ucaugccuuu u 21
<210> 2360
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2360
aaggcaugaa gcaggaacau u 21
<210> 2361
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2361
guuccugcuu caugccuuuu u 21
<210> 2362
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2362
aaaggcauga agcaggaacu u 21
<210> 2363
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2363
uuccugcuuc augccuuuuu u 21
<210> 2364
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2364
aaaaggcaug aagcaggaau u 21
<210> 2365
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2365
uuccugcuuc augccuuuau u 21
<210> 2366
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2366
uaaaggcaug aagcaggaau u 21
<210> 2367
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2367
uccugcuuca ugccuuucuu u 21
<210> 2368
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2368
agaaaggcau gaagcaggau u 21
<210> 2369
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2369
ccugcuucau gccuuucuau u 21
<210> 2370
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2370
uagaaaggca ugaagcaggu u 21
<210> 2371
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2371
cugcuucaug ccuuucuauu u 21
<210> 2372
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2372
auagaaaggc augaagcagu u 21
<210> 2373
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2373
cugcuucaug ccuuucuaau u 21
<210> 2374
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2374
uuagaaaggc augaagcagu u 21
<210> 2375
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2375
ugcuucaugc cuuucuacau u 21
<210> 2376
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2376
uguagaaagg caugaagcau u 21
<210> 2377
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2377
gcuucaugcc uuucuacauu u 21
<210> 2378
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2378
auguagaaag gcaugaagcu u 21
<210> 2379
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2379
gcuucaugcc uuucuacaau u 21
<210> 2380
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2380
uuguagaaag gcaugaagcu u 21
<210> 2381
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2381
cuucaugccu uucuacaguu u 21
<210> 2382
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2382
acuguagaaa ggcaugaagu u 21
<210> 2383
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2383
uucaugccuu ucuacaguuu u 21
<210> 2384
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2384
aacuguagaa aggcaugaau u 21
<210> 2385
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2385
uucaugccuu ucuacaguau u 21
<210> 2386
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2386
uacuguagaa aggcaugaau u 21
<210> 2387
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2387
ucaugccuuu cuacaguguu u 21
<210> 2388
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2388
acacuguaga aaggcaugau u 21
<210> 2389
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2389
ucaugccuuu cuacagugau u 21
<210> 2390
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2390
ucacuguaga aaggcaugau u 21
<210> 2391
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2391
caugccuuuc uacagugguu u 21
<210> 2392
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2392
accacuguag aaaggcaugu u 21
<210> 2393
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2393
caugccuuuc uacaguggau u 21
<210> 2394
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2394
uccacuguag aaaggcaugu u 21
<210> 2395
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2395
augccuuucu acaguggcuu u 21
<210> 2396
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2396
agccacugua gaaaggcauu u 21
<210> 2397
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2397
augccuuucu acaguggcau u 21
<210> 2398
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2398
ugccacugua gaaaggcauu u 21
<210> 2399
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2399
ugccuuucua caguggccuu u 21
<210> 2400
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2400
aggccacugu agaaaggcau u 21
<210> 2401
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2401
gccuuucuac aguggccuuu u 21
<210> 2402
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2402
aaggccacug uagaaaggcu u 21
<210> 2403
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2403
gguauguucc ugcuucaucu u 21
<210> 2404
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2404
gaugaagcag gaacauaccu u 21
<210> 2405
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2405
guauguuccu gcuucauccu u 21
<210> 2406
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2406
ggaugaagca ggaacauacu u 21
<210> 2407
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2407
uauguuccug cuucaucccu u 21
<210> 2408
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2408
gggaugaagc aggaacauau u 21
<210> 2409
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2409
auguuccugc uucauccccu u 21
<210> 2410
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2410
ggggaugaag caggaacauu u 21
<210> 2411
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2411
uguuccugcu ucauccccuu u 21
<210> 2412
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2412
aggggaugaa gcaggaacau u 21
<210> 2413
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2413
guuccugcuu cauccccuuu u 21
<210> 2414
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2414
aaggggauga agcaggaacu u 21
<210> 2415
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2415
uuccugcuuc auccccuucu u 21
<210> 2416
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2416
gaaggggaug aagcaggaau u 21
<210> 2417
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2417
uccugcuuca uccccuucuu u 21
<210> 2418
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2418
agaaggggau gaagcaggau u 21
<210> 2419
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2419
ccugcuucau ccccuucuau u 21
<210> 2420
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2420
uagaagggga ugaagcaggu u 21
<210> 2421
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2421
cugcuucauc cccuucuacu u 21
<210> 2422
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2422
guagaagggg augaagcagu u 21
<210> 2423
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2423
ugcuucaucc ccuucuacau u 21
<210> 2424
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2424
uguagaaggg gaugaagcau u 21
<210> 2425
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2425
gcuucauccc cuucuacagu u 21
<210> 2426
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2426
cuguagaagg ggaugaagcu u 21
<210> 2427
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2427
cuucaucccc uucuacaguu u 21
<210> 2428
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2428
acuguagaag gggaugaagu u 21
<210> 2429
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2429
uucauccccu ucuacagugu u 21
<210> 2430
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2430
cacuguagaa ggggaugaau u 21
<210> 2431
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2431
ucauccccuu cuacaguggu u 21
<210> 2432
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2432
ccacuguaga aggggaugau u 21
<210> 2433
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2433
cauccccuuc uacaguggcu u 21
<210> 2434
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2434
gccacuguag aaggggaugu u 21
<210> 2435
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2435
auccccuucu acaguggccu u 21
<210> 2436
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2436
ggccacugua gaaggggauu u 21
<210> 2437
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2437
uccccuucua caguggccuu u 21
<210> 2438
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2438
aggccacugu agaaggggau u 21
<210> 2439
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2439
ccccuucuac aguggccuuu u 21
<210> 2440
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 2440
aaggccacug uagaaggggu u 21
Claims (41)
- 센스 가닥 및 안티센스 가닥을 포함하는 RNAi 작제물로서, 상기 안티센스 가닥은 표 1 또는 2에 열거된 안티센스 서열과 3개 이하의 뉴클레오티드가 상이한 적어도 15개의 인접 뉴클레오티드를 갖는 영역을 포함하고, 상기 RNAi 작제물이 파타틴-유사 포스포리파제 도메인-함유 3(PNPLA3)의 발현을 억제하는, RNAi 작제물.
- 제1항에 있어서,
상기 안티센스 가닥이 PNPLA3 mRNA 서열에 상보적인 영역을 포함하는, RNAi 작제물. - 제1항 또는 제2항에 있어서,
상기 센스 가닥은 표 1 또는 2에 열거된 안티센스 서열과 3개 이하의 뉴클레오티드가 상이한 적어도 15개의 인접 뉴클레오티드를 갖는 영역을 포함하는, RNAi 작제물. - 제1항 내지 제3항 중 어느 한 항에 있어서,
상기 작제물은 PNPLA3-rs738409 소수 대립유전자를 우선적으로 억제하는, RNAi 작제물. - 제4항에 있어서,
상기 작제물은 다수 대립유전자와 비교하여 PNPLA3-rs738409 소수 대립유전자의 적어도 10% 더 큰 억제를 갖는, RNAi 작제물. - 제1항 내지 제5항 중 어느 한 항에 있어서,
상기 작제물은 PNPLA3-rs738408 소수 대립유전자를 우선적으로 억제하는, RNAi 작제물. - 제6항에 있어서,
상기 작제물은 다수 대립유전자와 비교하여 PNPLA3-rs738409-rs738408 이중 소수 대립유전자의 적어도 10% 더 큰 억제를 갖는, RNAi 작제물. - 제1항 내지 제7항 중 어느 한 항에 있어서,
상기 센스 가닥은 안티센스 가닥의 서열에 충분히 상보적인 서열을 포함하여 길이가 약 15 내지 약 30개의 염기쌍인 이중체 영역을 형성하는, RNAi 작제물. - 제8항에 있어서,
상기 이중체 영역은 길이가 약 17 내지 약 24개의 염기쌍인, RNAi 작제물. - 제8항에 있어서,
상기 이중체 영역은 길이가 약 19 내지 약 21개의 염기쌍인, RNAi 작제물. - 제10항에 있어서,
상기 이중체 영역은 길이가 19개의 염기쌍인, RNAi 작제물. - 제8항 내지 제11항 중 어느 한 항에 있어서,
상기 센스 가닥 및 안티센스 가닥은 각각 약 15 내지 약 30개의 뉴클레오티드 길이인, RNAi 작제물. - 제12항에 있어서,
상기 센스 가닥 및 안티센스 가닥은 각각 약 19 내지 약 27개의 뉴클레오티드 길이인, RNAi 작제물. - 제12항에 있어서,
상기 센스 가닥 및 안티센스 가닥은 각각 약 21 내지 약 25개의 뉴클레오티드 길이인, RNAi 작제물. - 제12항에 있어서,
상기 센스 가닥 및 안티센스 가닥은 각각 약 21 내지 약 23개의 뉴클레오티드 길이인, RNAi 작제물. - 제1항 내지 제15항 중 어느 한 항에 있어서,
상기 RNAi 작제물은 적어도 하나의 평활 말단을 포함하는, RNAi 작제물. - 제1항 내지 제15항 중 어느 한 항에 있어서,
상기 RNAi 작제물은 1 내지 4개의 짝없는 뉴클레오티드의 적어도 하나의 뉴클레오티드 오버행을 포함하는, RNAi 작제물. - 제17항에 있어서,
상기 뉴클레오티드 오버행은 2개의 짝없는 뉴클레오티드를 갖는, RNAi 작제물. - 제17항 또는 제18항에 있어서,
상기 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. - 제17항 내지 제19항 중 어느 한 항에 있어서,
상기 뉴클레오티드 오버행은 5'-UU-3' 디뉴클레오티드 또는 5'-dTdT-3' 디뉴클레오티드를 포함하는, RNAi 작제물. - 제1항 내지 제20항 중 어느 한 항에 있어서,
상기 RNAi 작제물은 적어도 하나의 변형된 뉴클레오티드를 포함하는, RNAi 작제물. - 제21항에 있어서,
상기 변형된 뉴클레오티드는 2'-변형된 뉴클레오티드인, RNAi 작제물. - 제21항에 있어서,
상기 변형된 뉴클레오티드는 2'-플루오로 변형된 뉴클레오티드, 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-O-알릴 변형된 뉴클레오티드, 이환식 핵산(BNA), 글리콜 핵산, 역전된 염기 또는 이들의 조합인, RNAi 작제물. - 제23항에 있어서,
상기 변형된 뉴클레오티드는 2'-O-메틸 변형된 뉴클레오티드, 2'-O-메톡시에틸 변형된 뉴클레오티드, 2'-플루오로 변형된 뉴클레오티드, 또는 이들의 조합인, RNAi 작제물. - 제21항에 있어서,
센스 및 안티센스 가닥의 모든 뉴클레오티드가 변형된 뉴클레오티드인, RNAi 작제물. - 제25항에 있어서,
변형된 뉴클레오티드는 2'-O-메틸변형된 뉴클레오티드, 2'-플루오로 변형된 뉴클레오티드, 또는 이들의 조합인, RNAi 작제물. - 제1항 내지 제26항 중 어느 한 항에 있어서,
상기 RNAi 작제물은 적어도 하나의 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물. - 제27항에 있어서,
상기 RNAi 작제물은 안티센스 가닥의 3' 말단에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물. - 제27항에 있어서,
상기 RNAi 작제물은 안티센스 가닥의 3' 및 5' 말단 양쪽에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결 및 센스 가닥의 5' 말단에 2개의 연속 포스포로티오에이트 뉴클레오티드간 연결을 포함하는, RNAi 작제물. - 제1항 내지 제29항 중 어느 한 항에 있어서,
상기 안티센스 가닥은 표 1 또는 표 2에 열거된 안티센스 서열로부터 선택된 서열을 포함하는, RNAi 작제물. - 제30항에 있어서,
상기 센스 가닥은 표 1 또는 표 2에 열거된 센스 서열로부터 선택된 서열을 포함하는, RNAi 작제물. - 제1항 내지 제31항 중 어느 한 항에 있어서,
상기 RNAi 작제물이 표 1 내지 2 중 어느 하나에 열거된 이중체 화합물 중 어느 하나인, RNAi 작제물. - 제1항 내지 제32항 중 어느 한 항에 있어서,
상기 RNAi 작제물은 대조군 RNAi 작제물과 함께 인큐베이션된 간 세포에서의 PNPLA3 발현 수준과 비교하여 RNAi 작제물과의 인큐베이션 후 간 세포에서의 PNPLA3의 발현 수준을 감소시키는, RNAi 작제물. - 제27항에 있어서,
상기 간 세포는 Hep3B 또는 HepG2 세포인, RNAi 작제물. - 제1항 내지 제26항 중 어느 한 항에 있어서,
상기 RNAi 작제물은 시험관내 Hep3B 세포에서 5 nM으로 PNPLA3 발현의 적어도 10%를 억제하는, RNAi 작제물. - 제1항 내지 제26항 중 어느 한 항에 있어서,
상기 RNAi 작제물은 시험관내 HepG2 세포에서 5 nM으로 PNPLA3 발현의 적어도 10%를 억제하는, RNAi 작제물. - 제1항 내지 제26항 중 어느 한 항에 있어서,
상기 RNAi 작제물은 약 1 nM 미만의 IC50으로 Hep3B 세포에서 PNPLA3 발현을 억제하는, RNAi 작제물. - 제1항 내지 제26항 중 어느 한 항에 있어서,
상기 RNAi 작제물은 약 1 nM 미만의 IC50으로 HepG2 세포에서 PNPLA3 발현을 억제하는, RNAi 작제물. - 제1항 내지 제38항 중 어느 한 항의 RNAi 작제물 및 약제학적으로 허용가능한 담체, 부형제 또는 희석제를 포함하는 약제학적 조성물.
- 제1항 내지 제38항 중 어느 한 항의 RNAi 작제물을, PNPLA3 발현의 감소를 필요로 하는 환자에게 투여하는 단계를 포함하는, 환자에서 PNPLA3 발현을 감소시키는 방법.
- 제40항에 있어서,
간세포에서 PNPLA3의 발현 수준은 RNAi 작제물을 수용하지 않는 환자에서의 PNPLA3 발현 수준과 비교하여 RNAi 작제물의 투여 후 환자에서 감소되는, 방법.
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