KR20170042625A - Myh7b의 억제제 및 이의 용도 - Google Patents

Myh7b의 억제제 및 이의 용도 Download PDF

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KR20170042625A
KR20170042625A KR1020177005777A KR20177005777A KR20170042625A KR 20170042625 A KR20170042625 A KR 20170042625A KR 1020177005777 A KR1020177005777 A KR 1020177005777A KR 20177005777 A KR20177005777 A KR 20177005777A KR 20170042625 A KR20170042625 A KR 20170042625A
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seq
antisense oligonucleotide
sequence
myh7b
nucleotides
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러스티 몽고메리
크리스티나 돌비
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미라젠 세러퓨틱스 인코포레이티드
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Abstract

본 발명은 MYH7B의 핵산 억제제 및 이의 조성물에 관한 것이다. 본 발명은 또한 MYH7B의 억제제를 대상에게 투여함으로써 심장비대증, 심근경색증 및 심부전증과 같은 심장 질환을 치료 또는 예방하는 방법을 제공한다. 본 발명은 MYH7B의 억제제를 대상에게 투여함으로써 대상의 심장 세포에서 β-MHC의 발현 또는 활성을 조절하는 방법을 추가로 제공한다.

Description

MYH7B의 억제제 및 이의 용도{Inhibitors of MYH7B and Uses Thereof}
본 발명은 마이오신 중쇄 유전자, MYH7B의 억제제 및 이의 조성물에 관한 것이다. 본 발명은 또한 MYH7B의 억제제를 투여함으로써 심장비대증, 심근경색증 및 심부전증과 같은 심장 질환을 치료 또는 예방하는 방법을 제공한다. 특히, 본 발명은 MYH7B의 핵산 억제제 및 이의 조성물, 및 필요한 대상에서 MYH7B의 발현 또는 활성을 억제함으로써 심장 질환을 치료 또는 예방하는 방법을 개시한다.
심장 질환은 미국에서 사망의 주원인이며 전세계 수백만 명의 사람들에게 큰 건강 위험을 제공한다. 비대성 심근병증, 심근경색증 및 심부전증을 포함하는 다양한 유형의 심장 질환으로 고통받는 환자를 진단, 치료 및 지원하는 비용은 매우 높으며 의료 시스템에 심각한 부담을 준다.
비대성 심근병증(HCM)은 불시의 돌발성 심장사의 중요한 원인이며 심장 마비가 발병하기 전에 종종 무증상이기 때문에 특별한 관심의 대상이다. HCM은 심실 기능에 영향을 미치고 심부정맥을 유발할 수 있는 심근 세포의 두꺼워짐을 특징으로 한다. HCM은 여러 가지 염색체 유전자에서 우성 돌연변이로 인해 발생하는 심장의 주요 유전 질환이며, 염색체 유전자 중 8개가 광범위하게 연구되고 있다(Teekakirikul et al., "Hypertrophic cardiomyopathy: translating cellular cross talk into therapeutics," J. Cell. Biol., 2012, 199(3), 417-421). HCM에서의 이러한 우성 돌연변이 중, 약 40%는 β-마이오신 유전자, MYH7의 미스센스 돌연변이이다. 유전학적 및 약리학적 연구는 이 우성 대립형질의 발현 감소가 매우 적지만 강력한 표현형 효과를 나타낼 수 있다는 것을 입증하였다(Jiang et al., "Allele-specific silencing of mutant MYH6 transcripts in mice suppresses hypertrophic cardiomyopathy," Science, 2013, 342(6154), 111-114).
마이오신은 심장과 골격근 세포의 주요 수축 단백질이다. 심장 근육 수축은 두 마이오신 중쇄(MHC) 단백질, α-MHC (MYH6) 및 β-MHC (MYH7)의 발현과 상대적 비율에 따라 결정된다. 설치류에서, α-MHC인 속근 MHC는 성인 심장에서 지배적인 마이오신 아이소폼인 반면, β-MHC인 지근 MHC는 성장하는 심장에서 주로 발현되고 출생 후 하향조절된다(Morkin, E., "Control of cardiac myosin heavy chain gene expression," Microsc. Res. Tech., 2000, 50, 522-531). 반면, 인간의 심장에서, β-MHC 아이소폼이 크게 발현되어 α-MHC 아이소폼은 전체 심실성 MHC의 8% 미만을 차지한다(Miyata et al., "Myosin heavy chain isoform expression in the failing and nonfailing human heart," Circ. Res., 2000, 86(4):386-90). 여러 종에서 알파- 및 베타-마이오신의 발현 차이와 관계없이, 연구는 베타-마이오신의 발현은 사람, 쥐 및 토끼를 포함하는 이들 종의 심장 질환에서 상향조절되는 것을 나타낸다. 예를 들어, 부전성 성체 생쥐 심장에서, 정상적으로 지배적인 알파-MHC에서 베타-MHC로의 이동이 종종 관찰된다(Harada et al., Circulation, 1999, 100, 2093-2099). 유사하게, 쥐에서 울혈성 심부전은 베타-마이오신의 증가된 발현 및 알파-MHC의 감소된 발현과 관련이 있다. 설치류 연구와 일치하여, 베타-마이오신 발현은 부전성 인간 심장에서 상향조절되었고 알파-마이오신 발현은 현저히 하향조절되었다(Miyata et al., "Myosin heavy chain isoform expression in the failing and nonfailing human heart," Circ. Res., 2000, 86(4):386-90). 이 연구는 알파- 및 베타-마이오신의 발현이 종에 의존적임에도 불구하고, 베타-마이오신의 발현을 하향 조절하는 것이 다양한 종에서 심장 보호 역할을 하는 것으로 나타낸다. 예를 들어, β-MHC 발현의 증가를 둔화시키고 α-MHC 발현을 증가시키는 것은 토끼에서 심장 보호적인 것으로 나타났다(James et al., "Forced expression of alpha-myosin heavy chain in the rabbit ventricle results in cardioprotection under cardiomyopathic conditions," Circulation, 2005, 111(18), 2339-2346).
α-MHC (MYH6), β-MHC (MYH7) 및 관련 마이오신인 MYH7B를 암호화하는 유전자는 또한 각각 인트론성 miRNA의 패밀리인 miR-208a, miR-208b 및 miR-499를 암호화한다. 이 세 가지 miR은 서열 상동성을 공유하며 "MyomiRs"라고 불린다(van Rooji et al., "A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance," Dev. Cell, 2009, 17, 662-673). MyomiR은 병적인 심장 리모델링, 근육 마이오신 함량, 근섬유 정체성 및 근 수행을 제어하는 것으로 나타났다(Liu and Olson, "MicroRNA regulatory networks in cardiovascular development," Dev. Cell, 2010, 510-525).
심장 및 근육 발달에 있어서 α-MHC, β-MHC 및 myomiR(miR-208a, miR-208b 및 miR-499)의 역할이 광범위하게 연구되었지만 세 번째 마이오신인 MYH7B의 역할은 크게 알려지지 않았다. MYH7B 유전자는 골격근, 심장 및 뇌에서 시냅스 구조와 기능을 조절하는 뇌 세포의 하부세트에서 발현된다(Yeung et al., “Myh7b/miR-499 gene expression is transcriptionally regulated by MRFs and Eos,” Nucleic Acids Res., 2012, 40(15):7303-18). 최근 보고는 MYH7b 단백질은 슬로우 토닉(slow-tonic) 섬유에 해당하는 외안근 및 근방추의 낭섬유에서 작은 섬유 집단으로 탐지되는 것을 제안한다(Rossi et al., "Two novel/ancient myosins in mammalian skeletal muscles: MYH14/7b and MYH15 are expressed in extraocular muscles and muscle spindles", J Physiol., Jan. 15, 2010; 588(Pt 2):353-64). 그러나, 인간의 심장에서 MYH7B 유전자는 비생산적 스플라이싱을 거쳐 기능성 MYH7B 단백질을 암호화할 수 없는 RNA를 생성한다고 생각된다(Bell et al., "Uncoupling of expression of an intronic microRNA and its myosin host gene by exon skipping," Mol. Cell. Biol., 30, 1937-1945). 흥미롭게도, 심장 세포에서 MYH7B mRNA의 비생산적인 스플라이싱은 인트론성 miR-499의 변형된 발현과 관련이 없었다. 따라서, 본 발명에 이르기까지, MYH7B는 심장 세포에서 miR-499의 비 기능성 운반체로 생각되었다(Gerald Dorn, II, "MicroRNAs: redefining mechanisms in cardiac disease," J. Cardiovasc. Pharmacol., 2010, 56(6), 589-595). 또한, miR-499와 달리 MYH7B는 심장 및 골격근 생물학에서 중요한 역할을 하지 않는 것으로 생각된다.
본 발명은 상기한 문제를 해결하는 것을 목적으로 한다.
본 발명은 부분적으로 MYH7B가 심장 세포에서 β-MHC의 발현을 조절하여 심장 수축성 및 스트레스-유도 심장 리모델링을 조절한다는 놀라운 발견에 기초한다. 특히, MYH7B의 억제는 심장 세포에서 β-MHC mRNA 및 단백질의 하향 조절을 초래한다. 따라서, 한 실시태양에서, 본 발명은 MYH7B 억제제, 이의 조성물, 및 MYH7B의 억제제를 대상에게 투여하는 단계를 포함하여 필요한 대상에서 β-MHC의 발현 및/또는 활성을 조절하는 방법을 제공한다. 한 실시태양에서, 대상에 대한 MYH7B의 억제제의 투여는 투여 후 대상의 심장 세포에서 MYH7B의 발현 또는 활성을 하향 조절한다. 한 실시태양에서, 대상에 대한 MYH7B의 억제제의 투여는 투여 후 대상의 심장 세포에서 β-MHC(MYH7)의 발현 또는 활성을 하향 조절한다. 다른 실시태양에서, 대상에 대한 MYH7B의 억제제를 투여는 투여 후 대상의 심장 세포에서 α-MHC(MYH6)의 발현 또는 활성을 상향 조절한다. 또 다른 실시태양에서, 대상에 대한 MYH7B의 억제제의 투여는 마이오신에 "전환(switch)"이 유도되어 β-MHC의 발현 또는 활성이 하향 조절되고 α-MHC의 발현 또는 활성이 투여 후 대상에서 상향 조절된다. 한 실시태양에서, 대상에 대한 MYH7B의 억제제의 투여는 대상의 심장 세포에서 miR-208a, miR-208b 또는 miR-499의 발현 또는 활성을 변화시키지 않는다.
또 다른 실시태양에서, 본 발명은 대상에게 MYH7B의 억제제를 투여하는 단계를 포함하여 병적 심장비대증, 심근경색증, 심부전증 또는 비대성 심근병증과 같은 심장 질환을 치료 또는 예방하기 위한 조성물 및 방법을 제공한다. 한 실시태양에 있어서, 심장 질환을 갖는 대상은 건강한 대상과 비교하여 심장 세포에서 β-MHC의 증가된 수준을 가졌다. 다른 실시태양에서, 심장 질환을 갖는 대상은 건강한 대상과 비교하여 심장 세포에서 β-MHC/α-MHC의 변형된 비율을 가진다. 한 실시태양에서, 심장 질환을 갖는 대상에 대한 MYH7B의 억제제의 투여는 투여 후 대상의 심장 세포에서 MYH7B의 발현 또는 활성 및/또는 MYH7의 발현 또는 활성을 억제한다. 다른 실시태양에서, 심장 질환를 갖는 대상에 대한 MYH7B 억제제를 투여는 투여 후 대상의 심장 세포에서 β-MHC/α-MHC 비율을 완전히 또는 부분적으로 정상 수준으로 회복한다. 한 실시태양에서, 심장 질환은 심근비대증, 심근경색증, 심부전증 또는 비대성 심근병증이다.
한 실시태양에서, MYH7B의 억제제는 안티센스 올리고뉴클레오티드, 앱타머, 리보자임, 소형 간섭 RNA(siRNA) 또는 소형 헤어핀 RNA(shRNA)로부터 선택되는 핵산 억제제이다. 다른 실시태양에서, MYH7B의 억제제는 MYH7B 단백질에 특이적으로 결합하는 항체 또는 이의 결합 단편이다. 특정 실시태양에서, MYH7B의 억제제는 MYH7B 암호화 서열에 적어도 부분적으로 상보적인 서열을 포함하는 안티센스 올리고뉴클레오티드이다. 본 발명의 조성물 및 방법에 사용되는 안티센스 올리고뉴클레오티드는 약 6 내지 약 22개 뉴클레오티드의 길이를 가질 수 있다. 일부 실시태양에서, 안티센스 올리고뉴클레티드는 당, 주쇄 및/또는 염기 변형과 같은 하나 이상의 화학적 변형을 포함한다.
한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 8 내지 18개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 SEQ ID NO: 6의 서열에 실질적으로 상보적이다.
일부 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 8 내지 18개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4300-4335로부터 SEQ ID NO: 6의 서열에 실질적으로 상보적이다.
일부 다른 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4300-4317로부터 SEQ ID NO: 6의 서열에 실질적으로 상보적이다.
또 다른 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4316-4333으로부터 SEQ ID NO: 6의 서열에 실질적으로 상보적이다.
한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 14개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4302-4315로부터 SEQ ID NO: 6의 서열에 실질적으로 상보적이다.
다른 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 14개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4318-4331로부터 SEQ ID NO: 6의 서열에 실질적으로 상보적이다.
일부 실시태양에서, 본 발명의 안티센스 올리고뉴클레오티드 억제제는 적어도 하나의 변형 뉴클레오티드를 함유한다. 변형 뉴클레오티드는 당, 염기 및/또는 주쇄 변형을 포함할 수 있다.
한 실시태양에서, 변형 뉴클레오티드는 잠금 뉴클레오티드이다. 일부 실시 태양에서, 안티센스 올리고뉴클레오티드 억제제는 1개 내지 6개의 잠금 뉴클레오티드를 함유한다. 일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 5' 말단의 적어도 처음 3개의 뉴클레오티드는 잠금 뉴클레오티드이다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 3' 말단의 적어도 처음 3개의 뉴클레오티드는 잠금 뉴클레오티드이다.
일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 5' 말단의 적어도 처음 3개 뉴클레오티드는 잠금 또는 비 잠금 리보뉴클레오티드이다. 일부 실시 태양에서, 안티센스 올리고뉴클레오티드 억제제의 3' 말단의 적어도 처음 3개 뉴클레오티드는 잠금 또는 비 잠금 리보뉴클레오티드이다.
한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 적어도 하나의 데옥시리보뉴클레오티드를 함유한다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 2 내지 8개의 데옥시리보뉴클레오티드를 함유한다.
다양한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 2'-O, 4'-C 메틸렌 가교, 2'-O, 4'-C 에틸렌 가교, 2'-CH2-NH-CH2-4' 가교, 2'-데옥시, 2'-O-알킬 및 2'-할로 변형으로 이루어진 그룹으로부터 선택된 당 변형을 포함할 수 있다.
다양한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 주쇄 변형을 포함할 수 있다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 적어도 하나의 포스포로티오에이트 결합을 함유한다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 2개 이상의 포스포로티오에이트 결합을 함유한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드는 완전히 포스포로티오에이트 결합된다.
한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 링커를 통해 연결된 펩타이드 또는 당 모이어티를 더 포함한다. 링커는 3'-티올-변형-C3- 다이설파이드 링커, (C6)2 다이설파이드 링커 또는 1-3 포스포다이에스터 결합일 수 있다.
특정 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 표 1-5로부터 선택된 서열을 포함한다.
한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 5'-lTslTslGsdAsdTsdCsdTsdTsdGsdGsdCslCslTslC-3'(SEQ ID NO: 146) 또는 5'-lCslTslGsdCsdAsdGsdCsdTsdCsdCsdTslCslCslA-3'(SEQ ID NO: 148)의 서열을 포함한다.
본 발명은 또한 MYH7B의 억제제 및 약학적으로 허용가능한 부형제를 포함하는 약학적 조성물을 제공한다. 한 실시태양에서, MYH7B의 억제제는 안티센스 올리고뉴클레오티드이다. 한 양태에서, 약학적 조성물은 miR-208a, miR-208b, miR-499, miR-15a, miR-15b, miR-16, miR-195 또는 이의 혼합물의 안티센스 올리고뉴클레오티드 억제제인 제 2 치료제를 더 포함한다.
본 발명은 MYH7B의 안티센스 올리고뉴클레오티드 억제제를 대상에게 투여하는 단계를 포함하여, 필요한 대상의 병적 심근비대증, 심근경색증 또는 심부전증을 치료 또는 예방하는 방법을 추가로 제공한다. 한 실시태양에서, 병적 심근비대증은 비대성 심근병증이다. 일부 실시태양에서, 본 발명에 따른 방법은 miR-208a, miR-208b, miR-499, miR-15a, miR-15b, miR-16, miR-195, 또는 이들의 조합의 안티센스 올리고뉴클레오티드 억제제와 같은 제 2 심장 치료제를 포함할 수 있다.
일부 실시태양에서, 본 발명은 병적 심근비대증의 위험이 있는 대상을 치료하는 방법을 제공한다. 한 실시태양에서, 병적 심근비대증의 위험이 있는 대상은 베타 마이오신 중쇄 유전자에서 돌연변이를 가진다.
한 양태에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제의 투여는 투여 후 대상의 심장 세포에서 MYH7B의 발현 또는 활성을 감소시킨다. 다른 양태에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제의 투여는 투여 후 대상의 심장 세포에서 베타 마이오신 중쇄의 발현을 감소시킨다. 또 다른 양태에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제의 투여는 투여 후 대상의 심장 세포에서 miR-499, miR-208a 및/또는 miR-208b의 발현을 현저하게 변화시키지 않는다.
일부 실시태양에서, 본 발명은 MYH7B의 억제제를 대상에게 투여하는 단계를 포함하여, 필요한 대상의 병적 심근비대증, 심근경색증 또는 심부전증을 치료 또는 예방하는 방법을 제공한다. 다양한 실시태양에서, MYH7B의 억제제는 안티센스 올리고뉴클레오티드, 앱타머, 리보자임, 소형 간섭 RNA 또는 소형 헤어핀 RNA로부터 선택되는 핵산 억제제이다.
한 실시태양에서, MYH7B의 핵산 억제제는 약 10 내지 약 30개 뉴클레오티드의 이중 가닥 영역을 포함하는 소형 간섭 RNA 또는 소형 헤어핀 RNA이며, 상기 이중 가닥 영역은 (i) 인간 Myh7b 유전자의 서열과 적어도 70% 동일한 서열을 갖는 제 1 RNA 가닥 및 (ⅱ) 제 1 RNA 가닥에 부분적으로, 실질적으로 또는 완전히 상보적인 제 2 RNA 가닥을 포함한다. 한 양태에서, siRNA 또는 shRNA의 제 1 RNA 가닥은 5'-GAGGCCAAGATCAA-3'(SEQ ID NO: 4)의 서열과 적어도 70% 동일한 서열을 가진다. 다른 양태에서, siRNA 또는 shRNA의 제 1 RNA 가닥은 5'-TGGAGGAGCTGCAG-3'(SEQ ID NO: 5)의 서열과 적어도 70% 동일한 서열을 가진다.
본 발명의 내용 중에 포함되어 있다.
도 1a는 MYH7B에 대한 안티센스 올리고뉴클레오티드에 의한 형질감염 48시간 후 인간 iPS 심근세포에서 MYH7B mRNA의 수준을 나타낸다. 도 1b는 MYH7B에 대한 안티센스 올리고뉴클레오티드에 의한 형질감염 48시간 후 인간 iPS 심근 세포에서 MYH7(β-MHC) mRNA의 수준을 나타낸다.
도 2a는 MYH7B에 대한 안티센스 올리고뉴클레오티드에 의한 형질감염 48시간 후 인간 iPS 심근세포에서 miR-208a의 수준을 나타낸다. 도 2b는 MYH7B에 대한 안티센스 올리고뉴클레오티드에 의한 형질감염 48시간 후 인간 iPS 심근세포에서 miR-499의 수준을 나타낸다. 도 2c는 MYH7B에 대한 안티센스 올리고뉴클레오티드에 의한 형질감염 48시간 후 인간 iPS 심근 세포에서의 miR-208b의 수준을 나타낸다.
도 3a는 MYH7B에 대한 안티센스 올리고뉴클레오티드에 의한 형질감염 48시간 후 대조군 및 HCM-R663H 심근세포에서 MYH7(β-MHC) mRNA의 수준을 나타낸다. 도 3b는 MYH7B에 대한 안티센스 올리고뉴클레오티드에 의한 형질감염 168시간(1 주) 후 대조군 및 HCM-R663H 심근세포에서 MYH7(β-MHC) mRNA의 수준을 나타낸다.
도 4는 치료 후 96시간에서 대조군 및 HCM iPS 심근세포로부터의 MYH7(β-MHC) 또는 GAPDH의 웨스턴 블롯 분석을 나타낸다.
도 5는 MYH7B에 대한 테스트 ASO 화합물에 의한 형질감염 48시간 후 인간 iPS 심근세포에서 MYH7B mRNA의 수준을 나타낸다.
도 6a는 MYH7B를 표적으로 하는 1, 5 또는 10μM 테스트 ASO 화합물(SEQ ID NOs. 92, 146, 32, 46 및 30)의 수동 투여 168시간 후 인간 iPS 심근세포에서 MYH7B mRNA의 수준을 나타낸다. 도 6b는 1, 5 또는 10μM 테스트 ASO 화합물의 수동 투여 168시간 후 인간 iPS 심근세포에서 MYH7(β-MHC) mRNA의 수준을 나타낸다. 도 6c는 1, 5 또는 10μM의 테스트 ASO 화합물의 수동 투여 168시간 후 인간 iPS 심근세포에서 MYH6(α-MHC) mRNA의 수준을 나타낸다.
도 7은 SEQ ID NO: 148의 서열을 갖는 5μM 테스트 ASO의 수동 투여 168시간 후 인간 iPS 심근 세포에서 MYH7B, MYH7(β-MHC) 및 MYH6(α-MHC) mRNA의 수준을 나타낸다.
도 8은 3일 연속으로 하루 당 25 mg/kg의 테스트 ASO를 주사하고 마지막 투여 48시간 후 희생시킨 쥐의 좌심실에서 MYH7B mRNA 수준을 나타낸다.
도 9a는 SEQ ID NO: 146 및 148의 서열을 포함하는 ASO 화합물로 치료된 토끼의 좌심실에서 MYH7B mRNA의 수준을 나타낸다. 도 9b는 SEQ ID NOs: 146 및 148의 서열을 포함하는 ASO 화합물로 치료된 토끼의 우심실에서 MYH7B mRNA의 수준을 나타낸다. 도 9c는 SEQ ID NOs: 146 및 148의 서열을 포함하는 ASO 화합물로 치료된 토끼의 좌심실에서의 MYH7(β-MHC) mRNA의 수준을 나타낸다. 도 9d는 SEQ ID NOs: 146 및 148의 서열을 포함하는 ASO 화합물로 치료된 토끼의 우심실에서 MYH7(β-MHC) mRNA의 수준을 나타낸다.
도 10a는 SEQ ID NO: 146의 서열을 포함하는 화합물에 기초한 ENA 변형 ASO의 수동 투여 48시간 후 인간 iPS 심근세포에서 MYH7B mRNA의 수준을 나타낸다. 도 10b는 SEQ ID NO: 146의 서열을 포함하는 화합물의 5-메틸 시티딘 및 2'-O-메틸 변형 ASO의 수동 투여 48시간 후 인간 iPS 심근 세포에서 MYH7B mRNA의 수준을 나타낸다. 도 10c는 SEQ ID NO: 146의 서열을 포함하는 화합물의 주쇄-변형 ASO의 수동 투여 48시간 후 인간 iPS 심근 세포에서 MYH7B mRNA의 수준을 나타낸다.
도 11a-11d는 MYH7B에 대한 테스트 ASO 화합물의 수동 투여 48시간 후 인간 iPS 심근 세포에서 MYH7B mRNA의 수준을 나타낸다.
본 발명자들은 지금까지 단지 miR-499의 비 기능성 담체로서 작용하는 것으로 생각된 MYH7B가 심장 세포에서 β-MHC의 발현 조절에 중요한 역할을 한다는 것을 발견하였다. 특히, 본 발명자들은 MYH7B의 억제가 심장 세포에서 β-MHC mRNA 및 단백질의 발현을 하향 조절한다는 것을 발견하였다. 따라서, 본 발명은 심장 질환, 특히 심장 근육 질환에 대한 치료적 개입을 위한 새로운 표적으로서 MYH7B를 제공한다.
본 발명은 MYH7B의 발현 또는 활성을 억제하는 제제를 제공한다. 다양한 실시태양에서, MYH7B를 억제하는 제제는 MYH7B 유전자, mRNA 또는 pre-mRNA를 표적으로 하는 핵산 억제제 또는 MYH7B 단백질을 표적으로 하는 항체 또는 그의 결합 단편이다. 특정 실시태양에서, MYH7B의 핵산 억제제는 안티센스 올리고뉴클레오티드, 앱타머, 리보자임, 소형 간섭 RNA 또는 소형 헤어핀 RNA로부터 선택된다.
한 실시태양에서, MYH7B의 억제제는 안티센스 올리고뉴클레오티드("ASO")이다. 본 발명의 내용에서, 용어 "안티센스 올리고뉴클레오티드" 또는 "ASO"는 광범위하게 사용되며, 유전자로부터 단백질로의 정보 전달을 억제하는 리보뉴클레오티드, 디옥시리보뉴클레오티드, 변형 리보뉴클레오티드, 변형 데옥시리보뉴클레오티드 또는 이들의 조합을 포함하는 올리고머를 포함한다. 본 발명에서 사용된 용어 "안티센스 올리고뉴클레오티드" 또는 "ASO"는 또한 전사 정지; 캡핑(capping), 스플라이싱(splicing), 핵에서 세포질로의 수송을 포함하는 다양한 단계에서의 pre-mRNA로부터의 mRNA 합성의 파괴; 갭머 ASO 또는 다른 RNAse H-유도 ASO에 의해 매개되는 것과 같은 mRNA의 분해; ASO가 표적 mRNA에 결합하여 번역에 사용할 수 없게 하는 번역 정지; 또는 표적 mRNA에 혼성화함으로써 표적 mRNA의 입체적 차단을 촉진시키는 리보뉴클레오티드, 데옥시리보뉴클레오티드, 변형 리보뉴클레오티드, 변형 데옥시리보뉴클레오티드 또는 이들의 조합을 포함하는 올리고머를 포함한다. 본 발명에서 사용된 용어 "안티센스 올리고뉴클레오티드"는 또한 링커를 통해 펩타이드 또는 당에 접합되거나 연결된 천연 및/또는 변형 뉴클레오티드를 함유하는 올리고머를 포함하는 안티센스 올리고뉴클레오티드 컨쥬게이트를 포함한다. 안티센스 올리고뉴클레오티드 컨쥬게이트를 제조하는데 사용될 수 있는 펩타이드 또는 당 모이어티 및 링커는 아래에서보다 상세히 설명된다.
다양한 실시태양에서, MYH7B의 활성을 억제하는데 유용한 안티센스 올리고뉴클레오티드는 약 5 내지 약 25개 뉴클레오티드 길이, 약 6 내지 약 22개 뉴클레오티드 길이, 약 10 내지 약 30개 뉴클레오티드 길이, 약 12 내지 약 20개 뉴클레오티드 길이, 또는 약 20 내지 약 25개 뉴클레오티드 길이이다. 특정 실시태양에서, MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드는 약 8 내지 약 18개 뉴클레오티드 길이이며, 다른 실시태양에서 약 12 내지 약 18개 뉴클레오티드 길이, 또 다른 실시태양에서 약 12개 내지 약 16개 뉴클레오티드 길이이다. 일부 실시태양에서, MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드는 약 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 또는 25개 뉴클레오티드 길이이다.
일부 실시태양에서, MYH7B에 대한 안티센스 올리고뉴클레오티드 억제제는 약 50 내지 약 150개 뉴클레오티드 길이, 약 60 내지 약 140개 뉴클레오티드 길이, 약 70 내지 약 130개 뉴클레오티드 길이, 약 80 내지 120개 뉴클레오티드 길이, 약 90 내지 약 110개 뉴클레오티드, 또는 약 100 내지 약 120개 뉴클레오티드 길이이다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 약 100 내지 약 120개 뉴클레오티드 길이이다. 특정 실시태양에서, MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드 억제제는 약 80, 90, 100, 110 또는 120개 뉴클레오티드 길이이다.
MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드는 생리학적 조건하에서 MYH7B에 혼성화하고 대상의 세포에서 MYH7B의 발현 또는 활성을 억제하기 위해 MYH7B 서열(DNA, mRNA 또는 pre-mRNA)에 적어도 부분적으로 또는 실질적으로 상보적인 서열을 포함한다. 예를 들어, 일부 실시태양에서, 안티센스 올리고뉴클레오티드는 MYH7B 유전자, mRNA 또는 pre-mRNA 서열에 적어도 부분적으로 상보적인, 예를 들어, MYH7B 유전자, mRNA 또는 pre-mRNA 서열에 적어도 약 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 또는 99% 상보적인 서열을 포함한다. 일부 실시태양에서, 안티센스 올리고뉴클레오티드는 MYH7B 유전자, mRNA 또는 pre-mRNA 서열에 실질적으로 상보적일 수 있는데, 즉 표적 뉴클레오티드 서열과 적어도 약 90%, 95%, 96%, 97%, 98% 또는 99% 상보적일 수 있다. 한 실시태양에서, 안티센스 올리고뉴클레오티드는 MYH7B 유전자, mRNA 또는 pre-mRNA 서열과 100% 또는 완전히 상보적인 서열을 포함한다. 특정 실시태양에서, MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드는 인간 MYH7B 유전자의 서열에 적어도 부분적으로, 실질적으로 또는 완전히 상보적인 서열을 포함한다. 일부 실시태양에서, MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드는 인간 MYH7B 유전자(진뱅크 수납번호 NM_020884.4; SEQ ID NO:6)의 암호화 서열에 적어도 부분적으로, 실질적으로 또는 완전히 상보적인 서열을 포함한다.
인간 MYH7B 암호화 서열(SEQ ID NO:6):
1 taggcttaaa gagcaggcgg ggcagagacc catacctttg gcgctgagtc gaggccagga
61 aggggcggtc gatgagaggg cggccttagc attaggagtg cgtcggctgc accctggcgg
121 atggaccttg ggaaggaggg gaggggacca tcggggtcgg cggggagcta cgggttcccc
181 tcttccaaga cgggtgccaa gtgatgagta tcaggtgtct atggtgagat ttggggagga
241 tcccagacct taacagccct ttggttgaaa cctctcacaa tgtggcagag atggggtttt
301 gatgtgttgc ccaggctggt cttgaactcc tgagcttaag tgatgtgtcc gcctgggcct
361 cccaaagtgc tggaattaca gacatgagtg gcaataaaag gggtagcaga gcttcctgcc
421 ctcaccgtgg tgccgagtgc ctgctgcctt gggccgcctt gaacctccag ggtttccagc
481 tcctcctcct tcaccccagt gccactgcca tgatggatgt gagtgaactt ggggagtctg
541 cccgctacct ccgccagggc taccaggaga tgacgaaggt gcacactatc ccatgggacg
601 ggaagaagcg agtctgggtg cctgatgaac aggacgccta cgtggaggcc gaggtcaagt
661 cggaggctac cgggggcaga gtcaccgtgg agaccaaaga ccagaaggtg ctgatggtgc
721 gtgaagccga gctgcagccc atgaacccgc ctcgcttcga cttactggag gacatggcca
781 tgatgacgca cctgaacgag gcctctgtgc tgcacaacct gcgccagcgc tatgcccgct
841 ggatgatcta tacctactca ggcctcttct gtgtcaccat caacccctac aaatggctcc
901 cagtctatac ggcctccgta gtggctgctt acaagggaaa gcgccgctca gattccccgc
961 cccatatata tgcggtggcg gacaacgcct acaacgacat gctgcgcaac cgagacaacc
1021 agtccatgct gatcaccgga gagtcggggg ccggtaagac ggttaacacc aagcgggtca
1081 ttcagtactt tgccatcgtc gctgccctgg gagacgggcc gggcaagaag gcccaatttc
1141 tggcaacaaa gacggggggc acccttgagg atcaaatcat cgaggccaac cctgccatgg
1201 aggcctttgg caacgccaag accctgagga atgataactc ctcccgcttt ggcaagttca
1261 tccgcattca ctttggtccc tctgggaagc tggcatccgc ggatattgac agctatctcc
1321 tggagaagtc gcgggtgatc ttccagttgc ctggtgagcg cagctaccat gtctactacc
1381 agatcctctc agggaggaag ccagagctgc aggacatgct gcttctgtct atgaacccct
1441 atgactacca cttctgcagc cagggcgtca tcaccgtgga caacatgaat gatggggagg
1501 agctcatcgc caccgaccat gccatggaca tcctaggctt cagcgtggat gagaaatgtg
1561 cctgctataa gatcgtgggc gccctcctgc actttggcaa catgaagttc aagcagaagc
1621 agcgggagga gcaggcggag gccgatggca ctgagagtgc tgacaaggct gcctacctga
1681 tgggggtcag cagtggggac ctcctcaaag gccttttgca cccccgggtg cgtgtaggga
1741 acgagtacgt gaccaagggc cagagtgtgg agcaggtggt gtttgctgtg ggggctctgg
1801 ccaaggccac ctatgaccgg ctgttcaggt ggctggtgtc tcggatcaac cagaccctgg
1861 acacaaagct gccccggcag ttcttcatcg gggttctgga catcgctggg tttgagatct
1921 ttgagttcaa cagcttcgaa cagctgtgca tcaacttcac caatgagaaa ttgcagcagt
1981 tcttcaacca gcacatgttt gtgctggagc aggaggagta caagcgggag ggcatcgact
2041 gggtcttcat cgacttcggc cttgacctgc agccttgcat cgacctcatc gagaagccac
2101 tgggcatcct gtccatcctg gaggaggaat gcatgttccc caaggcctca gacgccagct
2161 tccgggccaa gctctacgac aaccacgcgg ggaagtcacc caatttccag cagcctcggc
2221 ctgacaagaa gcgcaagtac caggcccact tcgaggtggt ccactacgca ggcgtggtgc
2281 cttacagcat tgtgggctgg ctggagaaaa acaaggatcc cctgaatgag accgtggtcc
2341 ccatcttcca gaagtcacag aataggctcc tggcgactct ctatgagaat tatgcgggct
2401 cctgctccac tgagcccccc aagtctgggg tgaaagagaa gcgtaagaag gcagcatcgt
2461 tccagacggt gtcccagctg cacaaggaga acctcaacaa gctgatgacc aacctgcggg
2521 ccacacagcc ccacttcgtc cgctgcattg tccccaacga gaacaaaacc ccaggggtca
2581 tggatgcctt cttggtgcta caccagctgc gctgcaatgg ggtcctggag gggatccgga
2641 tctgccgcca agggttcccc aacaggttgc tctacaccga cttccggcag cggtaccgta
2701 tcctgaaccc cagtgccatc ccggatgaca ccttcatgga cagcaggaag gccacagaga
2761 aactgctggg ctcgctggac ttggatcaca cccagtacca gtttggccac accaaggtgt
2821 tcttcaaggc tgggcttcta ggcgtcctgg aagagctccg tgaccagcgc ctggccaagg
2881 tgctgacgct gctgcaggcg cggagccgtg gccgcctcat gcgccttgag taccagcgcc
2941 tgctgggagg cagggatgcg ctgttcacca tccagtggaa catccgtgcc ttcaatgccg
3001 tcaagaactg gtcatggatg aagctctttt tcaagatgaa gccgctgctg cgctcggcgc
3061 aggctgagga ggagctggcg gccctgcggg cagagctgcg ggggttgcga ggggcgctgg
3121 ctgcggccga ggccaagcgc caggaactgg aggagacgca cgtcagcatc acccaggaga
3181 agaatgacct ggccctgcag ctgcaggctg agcaggacaa cctggcagat gccgaggagc
3241 gctgccactt gctgatcaag tccaaggtgc agctggaggg gaaggtgaag gagctgagtg
3301 agcggctgga ggatgaggag gaggtgaacg ctgacctggc cgcccgccgg cgcaagctgg
3361 aggacgagtg cacggagctc aagaaggaca ttgatgacct ggagctgaca ctggccaaag
3421 ctgagaagga gaagcaagcc actgagaaca aggtgaagaa cctgacggaa gagatggctg
3481 cgctggacga gtcagtggcc cggctgacca aggagaagaa ggcgttgcag gaggcccacc
3541 aacaggccct gggtgacctg caggccgagg aggaccgtgt gagcgcgctg accaaggcca
3601 agctccggct ggagcaacag gtggaggacc tggaatgctc cctggagcag gagaagaagc
3661 tgcgcatgga cacggagcgg gccaagcgca agctggaggg tgacctgaag ctgacgcagg
3721 agtcggtggc tgatgctgct caagacaagc agcagctgga ggagaagctc aagaagaagg
3781 actccgagct gagccagctg agcctgcggg tggaagacga gcagctcttg ggggcccaga
3841 tgcagaagaa gatcaaggag ctgcaggctc gggcggagga gctggaagag gagctggagg
3901 cagagcgggc agcccgggcc cgcgtggaga agcagcgtgc agaggcggcg cgggagctgg
3961 aggagctgag cgagcggctg gaggaggcag gcggcgcatc cgcggggcag cgcgagggct
4021 gccgcaagcg ggaggcggag ctggggaggc tgcggcggga gctggaggag gcggcgctgc
4081 ggcacgaggc cacagtggcg gcactgcggc gcaagcaggc ggagggcgcg gcggagctgg
4141 gggagcaggt ggacagcctg cagcgggtgc ggcagaagct ggagaaggag aagagtgagc
4201 tgcgcatgga ggtggacgac ctggctgcca acgtggagac tctgacccgc gccaaggcca
4261 gtgcagagaa gctgtgccgg acctatgagg atcagctaag cgaggccaag atcaaggtgg
4321 aggagctgca gcggcagctg gcggacgcaa gcacgcagcg tgggcgacta cagacggaaa
4381 gcggggagct gagtcgcctg ctagaggaga aggagtgtct gatcagtcag ctgagccgtg
4441 gaaaggccct ggccgcccaa agcctggaag agttgcggcg ccagctagag gaggaaagca
4501 aggccaagag tgccctggcc cacgccgtgc aggctctgcg gcacgactgt gacctcctgc
4561 gggagcaaca cgaggaggag gctgaggccc aggctgagct gcagcggctg ctgtccaagg
4621 ccaatgccga ggtggcccag tggaggagca agtacgaagc agatgccatc cagaggaccg
4681 aggagctgga ggaggccaaa aaaaagctgg cactgcggct gcaggaggca gaggagggcg
4741 tggaggctgc caacgccaag tgctcatcgt tggagaaggc caagctgcgg ctacagacag
4801 agtcagagga tgtaaccctg gagctggagc gggcgacctc agcagctgct gcgctggaca
4861 agaagcagcg gcacttggaa cgggcactgg aggaacggcg gcggcaggag gaggagatgc
4921 agcgggagct ggaggcggca cagagggagt cccgtggcct gggcaccgag ctcttccggc
4981 tgcggcacgg ccacgaggag gcacttgaag ccctggagac gctcaagcgg gagaacaaga
5041 acctgcagga ggagatcagc gacctcacag accaggtgag tctcagtggg aagagcatcc
5101 aggaactgga gaaaaccaag aaggcgctgg aaggcgagaa gagtgagatc caggctgcac
5161 tggaggaggc agagggggcc ctggagctgg aggagaccaa gacgctgcgg atccagctgg
5221 agctctccca ggtcaaagca gaagtggacc ggaagctggc agagaaagac gaggagtgcg
5281 ctaacctgag gcgcaaccac cagcgagctg tggagtccct gcaggcctcc ctggatgcag
5341 agacacgggc ccgcaatgag gcgctgcggc tcaagaagaa gatggagggt gacctcaacg
5401 acctggagct gcagctgggc catgccaccc gtcaggccac agaggcccag gctgccacgc
5461 ggctgatgca ggcacagctc aaggaggagc aggcagggcg ggacgaggag cagcggctgg
5521 cagctgagct ccacgagcag gcgcaggctc tggagcgccg ggcctcgctg ctggctgcgg
5581 agctggagga gctgcgggct gccctggagc agggcgagcg cagccggcga ctggcagagc
5641 aggagctttt ggaggccacc gagcgcctca accttctgca ttcgcagaac acaggcctcc
5701 taaaccagaa gaagaagctg gaggcggact tggcccagct gagcggggag gtggaggagg
5761 ctgcacagga gaggcgggag gctgaggaga aggccaaaaa ggccatcact gatgcggcca
5821 tgatggccga ggagctgaag aaggagcagg acacaagtgc acacctggaa cggatgaaga
5881 agacgctgga gcagacggtg cgcgagctcc aggcccgcct tgaggaggca gaacaggccg
5941 ccctccgtgg cgggaagaag caggtgcaga agctggaggc caaggtacgg gagctggagg
6001 ctgagcttga tgcagagcag aagaagcacg ccgaggccct taagggcgtg cgcaagcatg
6061 agcgccgtgt caaggagctc gcataccagg ccgaggagga caggaagaac ctggctcgca
6121 tgcaggacct ggtggacaag ctgcagagca aggtcaagag ctacaagcgc cagtttgagg
6181 aggcggagca gcaggccaac accaacctgg ccaagtatcg caaggcccag cacgagctgg
6241 atgatgcgga ggagcgggca gacatggcgg aaacccaggc caacaagctg cgggcacgga
6301 cccgggacgc cctgggcccc aagcacaagg agtgacggcc tgaccccctg ggctctaaag
6361 aggaatgtct gctgttgcac atctggctga ggccacctgc cccgatcctg ccatctctgc
6421 atcgccccct gctgccttca gccttccctg ggccctgaat aaacaccaca gccagtttcc
6481 ttctcattct tttctttggg gttcaggagg aaaaacacag tcctagggac aaaagccagg
6541 tccacagcag tcatttttaa aataaagtta tttaatagtc tccaaaaaaa aaaaaaaaaa
6601 aa
안티센스 올리고뉴클레오티드 서열이 자연 발생 뉴클레오티드 대신에 변형 뉴클레오티드를 포함하는 경우에도, 안티센스 올리고뉴클레오티드 억제제의 서열은 MYH7B 유전자, mRNA 또는 pre-mRNA 서열에 상보적인 것으로 생각되는 것이 이해된다. 예를 들어, MYH7B 유전자, mRNA 또는 pre-mRNA 서열이 특정 위치에서 구아노 신 뉴클레오티드를 포함하는 경우, 안티센스 올리고뉴클레오티드 억제제는 상응하는 위치에 잠금 시티딘 뉴클레오티드 또는 2'-플루오로-시티딘과 같은 변형 시티 딘 뉴클레오티드를 포함할 수 있다.
한 실시태양에서, 본 발명은 MYH7B의 안티센스 올리고뉴클레오티드 억제제를 제공하며, 상기 안티센스 올리고뉴클레오티드는 8 내지 18개 뉴클레오티드의 길이를 가지며 안티센스 올리고뉴클레오티드의 서열은 SEQ ID NO: 6에 실질적으로 상보적이다.
한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 8 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4300-4335로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다.
특정 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-18개 뉴클레오티드의 길이를 가지며, 뉴클레오티드 4300-4317, 4300-4316, 4301-4316, 4301-4315, 4302-4317, 4302-4316, 또는 4302-4315로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4302-4315로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 14개 뉴클레오티드의 길이를 가지며 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4302-4315로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적이다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lTslTslGsdAsdTsdCsdTsdTsdGsdGsdCslCslTslC-3'(SEQ IN NO: 146)의 서열을 포함하며, 여기서 l = 잠금 핵산 변형, d = 데옥시뉴클레오티드 및 s = 포스포로티오에이트 결합이다.
특정 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4316-4333, 4316-4332, 4317-4332, 4317-4331, 4318-4333, 4318-4332 또는 4318-4331로부터의 SEQ IN NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4318-4331로부터의 SEQ IN NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 일부 실시태양에서, 안티센스 올리고뉴클레오티드는 14개 뉴클레오티드의 길이를 가지며 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4318-4331로부터의 SEQ IN NO: 6의 서열에 실질적으로 상보적이다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lCslTslGsdCsdAsdGsdCsdTsdCsdCsdTslCslCslA-3'(SEQ IN NO: 148)의 서열을 포함한다.
일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 8 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1762-1783으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1762-1779, 1763-1779, 1764-1781, 1765-1780 또는 1766-1779로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1764-1777 또는 1766-1779로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lAslCslCsdTsdGsdCsdTsdCsdCsdAsdCslAslCslT-3'(SEQ ID NO: 62)의 서열을 포함한다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lCslCslAsdCsdCsdTsdGsdCsdTsdCsdCslAsslCslA-3'(SEQ ID NO: 64)의 서열을 포함한다.
일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 8 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 511-538으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 511-532, 512-530, 513-526, 514-528, 514-527, 515-530, 515-529 또는 515-528로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 513-526, 514-527 또는 515-528로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 521-538, 522-538, 522-537, 523-538, 523-537 또는 523-536으로부터의 SEQ IN NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 522-537 또는 523-536으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lTslCslAsmdCsdTsmdCsdAsmdCsdAsdTsmdCslCslAslT-3'(SEQ ID NO: 184)의 서열을 포함하며, 여기서 md = 5-메틸시토신이다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lTslTslCsdAsmdCsdTsmdCsdAsmdCsdAsdTslCslCslA-3'(SEQ ID NO: 186)의 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lGslTslTsmdCsdAsmdCsdTsmdCsdAsmdCsdAslTslCslC-3'(SEQ ID NO: 188)의 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lCslTslCsmdCsmdCsmdCsdAsdAsdGsdTsdTslCslAlC-3'(SEQ ID NO: 204)의 서열을 포함한다.
특정 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 8 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1640-1701로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1643-1660, 1648-1665, 1653-1670 또는 1694-1711의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 일부 실시태양에서, 안티센스 올리고뉴클레오드 억제제는 12 내지 14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1645-1658, 1650-1663, 1655-1668 또는 1696-1709의 SEQ ID NO: 6의 서열과 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lAslCslTsmdCsdTsmdCsdAsdGsdTsdGsmdCslCslAslT-3'(SEQ ID NO: 230)의 서열을 포함한다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lTslCslAsdGsmdCsdAsmdCsdTsmdCsdTsmdCslAslGslT-3'(SEQ ID NO; 238)의 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lCslCslTsdTsdGsdTsmdCsdAsdGsmdCsdAslCslTslC-3'(SEQ ID NO: 244)의 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lTslTslTsdGsdAsdGsdGsdAsdGsdGsdTslCslCslC-3'(SEQ ID NO: 272)의 서열을 포함한다.
일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4280-4300으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4280-4297, 4282-4295, 4283-4300 또는 4283-4296으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lCslTslGsdAsdTsmdCsmdCsdTsmdCsdAsdTslAslGslG-3'(SEQ ID NO: 304)의 서열을 포함한다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lGslCslTsdGsdAsdTsmdCsmdCsdTsmdCsdAslTslAslG-3'(SEQ ID NO: 306)의 서열을 포함한다.
일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 688-705, 689-706, 690-707 또는 690-703으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lTslGslGsdTsmdCsdTsdTsdTsdGsdGsdTslCslTslC-3'(SEQ ID NO: 344)의 서열을 포함한다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 890-907, 892-909 또는 892-905로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'- lGslAslCsdTsdGsdGsdGsdAsdGsmdCsmdCslAslTslT-3'(SEQ ID NO: 350)의 서열을 포함한다.
일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1217-1234, 1218-1235, 1219-1236, 또는 1219-1232로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lAslTslTsmdCsmdCsdTsmdCsdAsdGsdGsdGslTslCslT-3'(SEQ ID NO: 362)의 서열을 포함한다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1224-1241, 1225-1242, 1226-1243 또는 1226-1239로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lAslGslTsdTsdAsdTsmdCsdAsdTsdTsmdCslCslTslC-3'(SEQ ID NO: 370)의 서열을 포함한다.
일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1415-1441로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1415-1432, 1416-1433, 1417-1434 또는 1417-1430으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lAslGslAsmdCsdAsdGsdAsdAsdGsmdCsdAslGslCslA-3'(SEQ ID NO: 396)의 서열을 포함한다. 일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 1422-1439, 1423-1440, 1424-1441 또는 1424-1437로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lGs1GslTsdTsmdCsdAsdTsdAsdGsdAsmdCslAslGslA-3'(SEQ ID NO: 410)의 서열을 포함한다.
일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 8 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 2348-2371로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 2348-2365, 2349-2364, 2348-2361, 2349-2366, 2350-2365, 2351-2366, 2352-2367, 2352-2365, 2353-2370, 2354-2369 또는 2354-2368로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 2349-2362 또는 2350-2363으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 2350-2363 또는 2351-2364로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 2352-2365로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12-14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 2353-2366 또는 2354-2367로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lAslTslTsmdCsdTsdGsdTsdGsdAsmdCsdTslTslCslT-3'(SEQ ID NO: 474)의 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lTslAslTsdTsmdCsdTsdGsdTsdGsdAsmdCslTslTslC-3'(SEQ ID NO: 476)의 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lCslTslAsdTsdTsmdCsdTsdGsdTsdGsdAslCslTslT-3'(SEQ ID NO: 478)의 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lGslCslCsdTsdAsdTsdTsmdCsdTsdGsdTslGslAlC-3'(SEQ ID NO: 482)의 서열을 포함한다.
일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 2442-2462로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 특정 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 14개 뉴클레오티드의 길이를 가지며 뉴클레오티드 2444-2457 또는 2445-2458로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lAslTslGsmdCsdTsdGsmdCsmdCsdTsdTsmdCslTslTslA-3'(SEQ ID NO: 508)의 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lGslAslTsdGsmdCsdTsdGsmdCsmdCsdTsdTslCslTslT-3'(SEQ ID NO: 510)의 서열을 포함한다.
일부 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4408-4432로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 다양한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 18개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4408-4425, 4409-4426, 4410-4425, 4411-4428, 4411-4427, 4412-4429, 4412-4428 또는 4413-4430으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 16개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4409-4424 또는 4410-4425로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 다른 실시 태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 16개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4411-4426 또는 4412-4427로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 12 내지 16개 뉴클레오티드의 길이를 가지며 뉴클레오티드 4413-4428로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 서열을 포함한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lAslTslCsdAsdGsdAsmdCsdAsmdCsdTsmdCslCslTslT-3'(SEQ ID NO: 570)의 서열을 포함한다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lTslGslAsdTsmdCsdAsdGsdAsmdCsdAsmdCslTslCslC-3'(SEQ ID NO: 572)의 서열을 포함한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 5'-lCslTslGsdAsdTsmdCsdAsdGsdAsmdCsdAslCslTslC-3'(SEQ ID NO: 574)의 서열을 포함한다.
일부 실시태양에서, MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드는 SEQ ID NO: 6의 뉴클레오티드 1182 내지 1213으로부터의 인간 MYH7B 유전자의 서열에 적어도 부분적으로 상보적이거나 완전히 상보적인 서열을 포함한다. 다른 실시태양에서, MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드는 SEQ ID NO: 6의 뉴클레오티드 1365 내지 1393으로부터 인간 MYH7B 유전자의 서열에 적어도 부분적으로 상보적이거나 완전히 상보적인 서열을 포함한다.
한 실시태양에서, MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드는 5'-GTGAATGCGGATGAA-3'(SEQ ID NO: 1)의 서열을 가진다. 다른 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드는 5'-GAAGTGGTAGTCATA-3'(SEQ ID NO: 2)의 서열을 가진다. 또 다른 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드는 5'-lGslTslGsdAsdAsdTsdGsdCsdGsdGsdAsdTsdGslAslA-3'(SEQ ID NO: 3)의 서열을 가진다.
본 발명에서 사용된 용어 "약"은 +/- 10% 및 더욱 바람직하게는 +/- 5%의 변화를 포함하는데, 이는 이런 변화가 본 발명을 실시하는데 적절하기 때문이다.
한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 적어도 하나의 포스포로티오에이트, 모르폴리노 또는 포스포노카복실레이트 인터뉴클레오티드 결합과 같은 적어도 하나의 주쇄 변형을 함유한다(예를 들어, 본 발명에 전문이 참조로 포함된 미국 특허 제 6,693,187호 및 제 7,067,641호 참조). 일부 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 2개 이상의 포스포로티오에이트 결합을 함유한다. 특정 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 완전히 포스포로티오에이트 연결된다. 선택적으로, 안티센스 올리고뉴클레오티드는 당-포스페이트 주쇄보다는 펩타이드-기초 주쇄를 함유하는 펩타이드 핵산 (PNA)을 포함할 수 있다.
한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 잠금 뉴클레오티드 또는 다른 당, 염기 및/또는 주쇄 변형을 함유하는 뉴클레오티드와 같은 적어도 하나의 변형 뉴클레오티드를 함유한다. 용어 "잠금 핵산", "잠금 핵산 유닛", "잠금 핵산 잔기", "LNA 유닛", "가교 핵산", "가교 뉴클레오티드", "BNA"는 본 발명에서 상호 교환하여 사용할 수 있으며 바이사이클릭 뉴클레오시드/뉴클레오티드 유사체를 의미할 수 있다. 구체적으로, "가교 핵산" 또는 "가교 뉴클레오티드"는 당 잔기의 2', 4'-위치 또는 3', 4'-위치에 가교를 함유하는 뉴클레오티드를 의미한다. 예를 들어, 적절한 안티센스 올리고뉴클레오티드 억제제는 가교 뉴클레오티드를 함유하는 올리고뉴클레오티드 및 이의 상보적인 표적 가닥 사이에 형성된 복합체에 향상된 열 안정성을 부여하는 하나 이상의 "입체적으로 제한된" 또는 2', 4'-가교 뉴클레오티드 변형으로 이루어질 수있다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 통상적으로 "잠금 뉴클레오티드" 또는 "LNA"로 공지된 2'-O, 4'-C-메틸렌 가교 리보뉴클레오시드(구조 A)를 함유한다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 적어도 하나의 2', 4'-C-가교 2'-데옥시리보뉴클레오시드(CDNA, 구조 B)를 함유한다. 예를 들어, 미국 특허 제 6,403,566호 및 Wang et al. (1999) Bioorganic and Medicinal Chemistry Letters, Vol. 9:1147-1150을 참조하기 바라며, 이들 둘 모두는 전문이 참조로 본 발명에 포함된다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 구조 C로 나타낸 구조를 갖는 적어도 하나의 변형 뉴클레오시드를 함유한다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 적어도 하나의 2'O, 4'-C- 에틸렌 가교 리보뉴클레오시드(구조 D)를 함유한다. 2'O, 4'-C-에틸렌 가교를 함유하는 핵산 또는 올리고뉴클레오티드 또는 뉴클레오티드는 또한 에틸렌 가교 핵산(ENA)으로 알려져있다. 또 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 "아미노-2'-C-가교 바이사이클릭 뉴클레오티드" 또는 "아미노-CBBN"으로도 알려진 적어도 하나의 2'-CH2-NH-CH2-4'-가교 뉴클레오티드를 함유한다. MYH7B를 표적으로 하는 안티센스 올리고뉴클레오티드 억제제는 상기 가교 뉴클레오티드 또는 다른 변형 뉴클레오티드 및 변형되지 않은 리보뉴클레오티드 또는 데옥시 리보뉴클레오티드의 조합을 함유할 수 있다.
Figure pct00001
본 발명의 내용에서 DNA 또는 RNA 뉴클레오티드를 이의 상응하는 가교 또는 잠금 뉴클레오티드로 치환하는 것을 언급할 때, "상응하는 가교 뉴클레오티드" 또는 "상응하는 잠금 뉴클레오티드"라는 용어는 DNA/RNA 뉴클레오티드가 대체된 DNA/RNA 뉴클레오티드와 동일한 자연 발생적 질소 함유 염기 또는 화학적으로 변형된 동일한 질소 함유 염기를 함유하는 가교 또는 잠금 뉴클레오티드에 의해 대체되었다는 것을 의미한다. 예를 들어, 질소 함유 염기 C를 함유하는 DNA 뉴클레오티드의 상응하는 가교 또는 잠금 뉴클레오티드는 동일한 질소 함유 염기 C 또는 5-메틸시토신과 같이 화학적으로 변형된 동일한 질소 함유 염기 C를 함유할 수 있다.
용어 "비-가교 뉴클레오티드" 또는 "비-잠금 뉴클레오티드"는 가교 또는 잠금 뉴클레오티드와 상이한 뉴클레오티드를 의미하는데, 즉 용어 "비-가교 뉴클레오티드" 또는 "비-잠금 뉴클레오티드"는 DNA 뉴클레오티드, RNA 뉴클레오티드뿐만 아니라 변형이 가교 또는 잠금 변형이 아닌 것을 제외하고 염기 및/또는 당이 변형된 변형 뉴클레오티드를 포함한다.
한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 적어도 하나의 잠금 뉴클레오티드를 함유한다. 일부 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드 억제제는 1개 내지 6개의 잠금 뉴클레오티드를 함유한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 3' 말단으로부터의 적어도 처음 3개 뉴클레오티드는 잠금 뉴클레오티드이다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 5' 말단으로부터의 적어도 처음 3개 뉴클레오티드는 잠금 뉴클레오티드이다.
특정 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 1 내지 6개의 천연 또는 변형 리보뉴클레오티드를 함유한다. 한 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 3'말단으로부터의 적어도 처음 3개 뉴클레오티드는 천연 또는 변형 리보뉴클레오티드이다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 5' 말단으로부터의 적어도 처음 3개 뉴클레오티드는 천연 또는 변형 리보뉴클레오티드이다. 일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 3' 말단으로부터의 처음 3개 뉴클레오티드는 잠금 리보뉴클레오티드이다. 다른 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 5' 말단으로부터의 처음 3개 뉴클레오티드는 잠금 리보뉴클레오티드이다.
본 발명의 올리고뉴클레오티드 억제제는 염기 변형 또는 치환을 갖는 변형 뉴클레오티드를 포함할 수 있다. 천연 또는 비 변형 염기는 퓨린 염기인 아데닌(A) 및 구아닌(G) 및 피리미딘 염기인 시토신(C), 티민(T) 및 우라실(U)이다. 헤테로 사이클릭 염기 모이어티로도 불리는 변형 염기는 5-메틸시토신(5-me-C), 5-하이드 록시메틸 시토신, 잔틴, 하이포잔틴, 2-아미노아데닌, 6-메틸 및 아데닌과 구아닌의 다른 알킬 유도체, 2-프로필 및 아데닌 및 구아닌의 다른 알킬 유도체, 2-티오우라실, 2-티오티민 및 2-티오시토신, 5-할로우라실 및 시토신, 5-프로핀일 우라실 및 시토신 및 피리미딘 염기의 다른 알킨일 유도체, 6-아조 우라실, 시토신 및 티민, 5-우라실(pseudouracil), 4-티오우라실, 8-할로, 8-아미노, 8-티올, 8-티오알킬, 8-하이드록실 및 다른 8-치환된 아데닌 및 구아닌, 5-할로(5-브로모, 5-트라이플루오로메틸 및 다른 5-치환 우라실 및 시토신 포함), 7-메틸구아닌 및 7-메틸아데닌, 2-F-아데닌, 2-아미노-아데닌, 8-아자구아닌 및 8-아자아데닌, 7-데아자구아닌 및 7-데아자아데닌 및 3-데아자구아닌 및 3-데아자아데닌과 같은 다른 합성 및 천연 핵염기를 포함한다. 한 실시태양에서, 본 발명의 안티센스 올리고뉴클레오티드 억제제는 1 내지 5개의 5-메틸시티딘 또는 5-메틸데옥시시티딘 뉴클레오티드를 포함한다. 특정 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 염기 변형 (예를 들어, 5- 메틸시티딘)과 함께 하나 이상의 가교 핵산 변형(예를 들어, LNA, ENA 등)을 포함한다.
본 발명의 올리고뉴클레오티드 억제제는 변형 당 모이어티를 갖는 뉴클레오티드를 포함할 수 있다. 대표적인 변형 당은 카보사이클릭 또는 비 사이클릭 당, 2', 3' 또는 4' 위치 중 하나 이상에 치환기를 갖는 당 및 당의 하나 이상의 수소 원자 대신 치환기를 갖는 당을 포함한다. 특정 실시태양에서, 당은 2' 위치에 치환기를 가짐으로써 변형된다. 추가의 실시태양에서, 당은 3' 위치에 치환기를 가짐으로써 변형된다. 다른 실시태양에서, 당은 4' 위치에 치환기를 가짐으로써 변형된다. 당이 이런 위치 중 하나 이상에서 변형을 가질 수 있거나 또는 올리고뉴클레오티드 억제제가 한 위치에서 당 변형을 갖는 하나 이상의 뉴클레오티드 및 상이한 위치에서 당 변형을 갖는 하나 이상의 뉴클레오티드를 가질 수 있다는 것도 또한 고려된다.
본 발명의 올리고뉴클레오티드 억제제에서 고려되는 당 변형은 OH; F; O-, S- 또는 N-알킬; O-, S- 또는 N-알켄일; O-, S- 또는 N-알카인일; 또는 O-알킬 -O- 알킬로부터 선택된 치환기를 포함하나 이에 제한되지 않으며, 알킬, 알켄일 및 알카인일은 C1 내지 C10 알킬 또는 C2 내지 C10 알켄일 및 알카인일로 치환되거나 비치 환될 수 있다. 한 실시태양에서, 변형은 2'-메톡시에톡시(2'-O-CH2CH2OCH3, 2'-O- (2-메톡시에틸) 또는 2'-MOE로도 알려짐), 즉 알콕시알콕시기를 포함한다. 다른 변형은 2'-다이메틸아미노옥시에톡시, 즉 2'-DMAOE 및 2'-다이메틸아미노에톡시에톡시(이 기술 분야에서 2'-O-다이메틸-아미노-에톡시-에틸 또는 2'-DMAEOE로 공지됨)로도 공지된 O(CH2)2ON(CH3)2기, 즉 2'-O-CH2-O-CH2-N(CH3)2를 포함한다.
추가의 당 치환기는 알릴(-CH2-CH=CH2), -O-알릴, 메톡시(-O-CH3), 아미노프로폭시(-OCH2CH2CH2NH2) 및 플루오로(F)를 포함한다. 2 '위치(2'-) 상의 당 치환기는 아라비노(위) 또는 리보(아래) 위치에 있을수 있다. 하나의 2'-아라비노 변형은 2'-F이다. 다른 유사한 변형이 당 모이어티 상의 다른 위치, 특히 3' 말단 뉴클레오시드 또는 2'-5' 연결 올리고뉴클레오티드에서 당의 3' 위치 및 5' 말단 뉴클레오티드의 5' 위치에서 이루어질 수 있다. 특정 실시태양에서, 당 변형은 2'-O-알킬 (예를 들어, 2'-O-메틸, 2'-O-메톡시에틸), 2'-할로(예를 들어, 2'-플루오로, 2'-클로로, 2'-브로모) 및 4' 티오 변형이다.
전문이 참조로 본 발명에 포함된 미국 특허 제 6,838,283호에 기술된 바와 같이, 안정성을 향상시키고 효능을 향상시키는 올리고뉴클레오티드 억제제의 다른 변형은 당해 기술분야에 공지되어 있으며 본 방법에서의 사용에 적합하다. 예를 들어, 생체 내 전달 및 안정성을 촉진하기 위해, 올리고뉴클레오티드 억제제는 이의3' 말단에서 콜레스테롤 모이어티, 비타민, 지방산, 탄수화물 또는 글리코시드, 펩타이드 또는 다른 소분자 리간드와 같은 스테로이드와 연결될 수 있다. 일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제는 표적 세포에 의한 억제제의 흡수를 증진시키기 위해 펩타이드에 부착된다. 예를 들어, 일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 3' 말단은 서열 "WLSEAGPVVTVRALRGTGSW"를 갖는 펩타이드에 부착된다. 이 펩타이드는 본 발명에 참조로 포함된 McGuire et al("In vitro selection of a peptide with high selectivity for cardiomyocytes in vivo", J. Mol. Bio, 2004, vol. 342, 171-182)에 기술된다. 한 실시태양에서, 펩타이드는 "thiolC3"과 같은 링커를 통해 안티센스 올리고에 부착되어, 티오에터 결합이 링커의 SH기와 펩타이드 상의 올리고 및 말레이미드 사이에 형성된다. 일부 실시태양에서, 안티센스 올리고뉴클레오티드 억제제의 5' 말단은 직접 또는 링커를 통해 당 모이어티에 부착될 수 있다. 링커는 C6-다이설파이드 링커 또는 포스포다이에스테 dTdT 링커와 같은 1-3 포스 포다이에스터 링커일 수 있다.
다양한 실시태양에서, MYH7B의 안티센스 올리고뉴클레오티드는 표 1 내지 5로부터 선택된 서열을 가진다.
SEQ ID NO: 6의 표적 서열의 시작 뉴클레오티드 서열(5'-3') 변형을 가진 서열(5'-3')
733 GTTCATGGGCTGCA
(SEQ ID NO: 7)		 lGslTslTsdCsdAsdTsdGsdGsdGsdCsdTslGslCslA
(SEQ ID NO: 8)
734 GGTTCATGGGCTGC
(SEQ ID NO: 9)		 lGslGslTsdTsdCsdAsdTsdGsdGsdGsdCslTslGslC
(SEQ ID NO: 10)
735 GGGTTCATGGGCTG
(SEQ ID NO: 11)		 lGslGslGsdTsdTsdCsdAsdTsdGsdGsdGslCslTslG
(SEQ ID NO: 12)
867 ATGGTGACACAGAA
(SEQ ID NO: 13)		 lAslTslGsdGsdTsdGsdAsdCsdAsdCsdAslGslAslA
(SEQ ID NO: 14)
1020 ATCAGCATGGACTG
(SEQ ID NO: 15)		 lAslTslCsdAsdGsdCsdAsdTsdGsdGsdAslCslTslG
(SEQ ID NO: 16)
1061 GCTTGGTGTTAACC
(SEQ ID NO: 17)		 lGslCslTsdTsdGsdGsdTsdGsdTsdTsdAslAslCslC
(SEQ ID NO: 18)
1188 TCCATGGCAGGGTT
(SEQ ID NO: 19)		 lTslCslCsdAsdTsdGsdGsdCsdAsdGsdGslGslTslT
(SEQ ID NO: 20)
1189 CTCCATGGCAGGGT
(SEQ ID NO: 21)		 lCslTslCsdCsdAsdTsdGsdGsdCsdAsdGslGslGslT
(SEQ ID NO: 22)
1190 CCTCCATGGCAGGG
(SEQ ID NO: 23)		 lCslCslTsdCsdCsdAsdTsdGsdGsdCsdAslGslGslG
(SEQ ID NO: 24)
1191 GCCTCCATGGCAGG
(SEQ ID NO: 25)		 lGslCslCsdTsdCsdCsdAsdTsdGsdGsdCslAslGslG
(SEQ ID NO: 26)
1305 AGATAGCTGTCAAT
(SEQ ID NO: 27)		 lAslGslAsdTsdAsdGsdCsdTsdGsdTsdCslAslAslT
(SEQ ID NO: 28)
1306 GAGATAGCTGTCAA
(SEQ ID NO: 29)		 lGslAslGsdAsdTsdAsdGsdCsdTsdGsdTslCslAslA
(SEQ ID NO: 30)
1307 GGAGATAGCTGTCA
(SEQ ID NO: 31)		 lGslGslAsdGsdAsdTsdAsdGsdCsdTsdGslTslCslA
(SEQ ID NO: 32)
1308 AGGAGATAGCTGTC
(SEQ ID NO: 33)		 lAslGslGsdAsdGsdAsdTsdAsdGsdCsdTslGslTslC
(SEQ ID NO: 34)
1309 CAGGAGATAGCTGT
(SEQ ID NO: 35)		 lCslAslGsdGsdAsdGsdAsdTsdAsdGsdCslTslGslT
(SEQ ID NO: 36)
1310 CCAGGAGATAGCTG
(SEQ ID NO: 37)		 lCslCslAsdGsdGsdAsdGsdAsdTsdAsdGslCslTslG
(SEQ ID NO: 38)
1311 TCCAGGAGATAGCT
(SEQ ID NO: 39)		 lTslCslCsdAsdGsdGsdAsdGsdAsdTsdAslGslCslT
(SEQ ID NO: 40)
1443 CAGAAGTGGTAGTC
(SEQ ID NO: 41)		 lCslAslGsdAsdAsdGsdTsdGsdGsdTsdAslGslTslC
(SEQ ID NO: 42)
1445 TGCAGAAGTGGTAG
(SEQ ID NO: 43)		 lTslGslCsdAsdGsdAsdAsdGsdTsdGsdGslTslAslG
(SEQ ID NO: 44)
1446 CTGCAGAAGTGGTA
(SEQ ID NO: 45)		 lCslTslGsdCsdAsdGsdAsdAsdGsdTsdGslGslTslA
(SEQ ID NO: 46)
1647 GCACTCTCAGTGCC
(SEQ ID NO: 47)		 lGslCslAsdCsdTsdCsdTsdCsdAsdGsdTslGslCslC
(SEQ ID NO: 48)
1662 TAGGCAGCCTTGTC
(SEQ ID NO: 49)		 lTslAslGsdGsdCsdAsdGsdCsdCsdTsdTslGslTslC
(SEQ ID NO: 50)
1755 ACACTCTGGCCCTT
(SEQ ID NO: 51)		 lAslCslAsdCsdTsdCsdTsdGsdGsdCsdCslCslTslT
(SEQ ID NO: 52)
1758 TCCACACTCTGGCC
(SEQ ID NO: 53)		 lTslCslCsdAsdCsdAsdCsdTsdCsdTsdGslGslCslC
(SEQ ID NO: 54)
1759 CTCCACACTCTGGC
(SEQ ID NO: 55)		 lCslTslCsdCsdAsdCsdAsdCsdTsdCsdTslGslGslC
(SEQ ID NO: 56)
1760 GCTCCACACTCTGG
(SEQ ID NO: 57)		 lGslCslTsdCsdCsdAsdCsdAsdCsdTsdCslTslGslG
(SEQ ID NO: 58)
1761 TGCTCCACACTCTG
(SEQ ID NO: 59)		 lTslGslCsdTsdCsdCsdAsdCsdAsdCsdTslCslTslG
(SEQ ID NO: 60)
1764 ACCTGCTCCACACT
(SEQ ID NO: 61)		 lAslCslCsdTsdGsdCsdTsdCsdCsdAsdCslAslCslT
(SEQ ID NO: 62)
1766 CCACCTGCTCCACA
(SEQ ID NO: 63)		 lCslCslAsdCsdCsdTsdGsdCsdTsdCsdCslAslCslA
(SEQ ID NO: 64)
1767 ACCACCTGCTCCAC
(SEQ ID NO: 65)		 lAslCslCsdAsdCsdCsdTsdGsdCsdTsdCslCslAslC
(SEQ ID NO: 66)
1912 CTCAAAGATCTCAA
(SEQ ID NO: 67)		 lCslTslCsdAsdAsdAsdGsdAsdTsdCsdTslCslAslA
(SEQ ID NO: 68)
1913 ACTCAAAGATCTCA
(SEQ ID NO: 69)		 lAslCslTsdCsdAsdAsdAsdGsdAsdTsdCslTslCslA
(SEQ ID NO: 70)
1914 AACTCAAAGATCTC
(SEQ ID NO: 71)		 lAslAslCsdTsdCsdAsdAsdAsdGsdAsdTslCslTslC
(SEQ ID NO: 72)
2037 ATGAAGACCCAGTC
(SEQ ID NO: 73)		 lAslTslGsdAsdAsdGsdAsdCsdCsdCsdAslGslTslC
(SEQ ID NO: 74)
2038 GATGAAGACCCAGT
(SEQ ID NO: 75)		 lGslAslTsdGsdAsdAsdGsdAsdCsdCsdCslAslGslT
(SEQ ID NO: 76)
2253 TAGTGGACCACCTC
(SEQ ID NO: 77)		 lTslAslGsdTsdGsdGsdAsdCsdCsdAsdCslCslTslC
(SEQ ID NO: 78)
2481 AGGTTCTCCTTGTG
(SEQ ID NO: 79)		 lAslGslGsdTsdTsdCsdTsdCsdCsdTsdTslGslTslG
(SEQ ID NO: 80)
2482 GAGGTTCTCCTTGT
(SEQ ID NO: 81)		 lGslAslGsdGsdTsdTsdCsdTsdCsdCsdTslTslGslT
(SEQ ID NO: 82)
2483 TGAGGTTCTCCTTG
(SEQ ID NO: 83)		 lTslGslAsdGsdGsdTsdTsdCsdTsdCsdCslTslTslG
(SEQ ID NO: 84)
2484 TTGAGGTTCTCCTT
(SEQ ID NO: 85)		 lTslTslGsdAsdGsdGsdTsdTsdCsdTsdCslCslTslT
(SEQ ID NO: 86)
2485 GTTGAGGTTCTCCT
(SEQ ID NO: 87)		 lGslTslTsdGsdAsdGsdGsdTsdTsdCsdTslCslCslT
(SEQ ID NO: 88)
2488 CTTGTTGAGGTTCT
(SEQ ID NO: 89)		 lCslTslTsdGsdTsdTsdGsdAsdGsdGsdTslTslCslT
(SEQ ID NO: 90)
2518 GGGCTGTGTGGCCC
(SEQ ID NO: 91)		 lGslGslGsdCsdTsdGsdTsdGsdTsdGsdGslCslCslC
(SEQ ID NO: 92)
2738 CCTTCCTGCTGTCC
(SEQ ID NO: 93)		 lCslCslTsdTsdCsdCsdTsdGsdCsdTsdGslTslCslC
(SEQ ID NO: 94)
2740 GGCCTTCCTGCTGT
(SEQ ID NO: 95)		 lGslGslCsdCsdTsdTsdCsdCsdTsdGsdCslTslGslT
(SEQ ID NO: 96)
2961 TGGATGGTGAACAG
(SEQ ID NO: 97)		 lTslGslGsdAsdTsdGsdGsdTsdGsdAsdAslCslAslG
(SEQ ID NO: 98)
2962 CTGGATGGTGAACA
(SEQ ID NO: 99)		 lCslTslGsdGsdAsdTsdGsdGsdTsdGsdAslAslCslA
(SEQ ID NO: 100)
2964 CACTGGATGGTGAA
(SEQ ID NO: 101)		 lCslAslCsdTsdGsdGsdAsdTsdGsdGsdTslGslAslA
(SEQ ID NO: 102)
2966 TCCACTGGATGGTG
(SEQ ID NO: 103)		 lTslCslCsdAsdCsdTsdGsdGsdAsdTsdGslGslTslG
(SEQ ID NO: 104)
2967 TTCCACTGGATGGT
(SEQ ID NO: 105)		 lTslTslCsdCsdAsdCsdTsdGsdGsdAsdTslGslGslT
(SEQ ID NO: 106)
3186 TGCAGGGCCAGGTC
(SEQ ID NO: 107)		 lTslGslCsdAsdGsdGsdGsdCsdCsdAsdGslGslTslC
(SEQ ID NO: 108)
3187 CTGCAGGGCCAGGT
(SEQ ID NO: 109)		 lCslTslGsdCsdAsdGsdGsdGsdCsdCsdAslGslGslT
(SEQ ID NO: 110)
3255 ACCTTGGACTTGAT
(SEQ ID NO: 111)		 lAslCslCsdTsdTsdGsdGsdAsdCsdTsdTslGslAslT
(SEQ ID NO: 112)
3257 GCACCTTGGACTTG
(SEQ ID NO: 113)		 lGslCslAsdCsdCsdTsdTsdGsdGsdAsdCslTslTslG
(SEQ ID NO: 114)
3258 TGCACCTTGGACTT
(SEQ ID NO: 115)		 lTslGslCsdAsdCsdCsdTsdTsdGsdGsdAslCslTslT
(SEQ ID NO: 116)
3259 CTGCACCTTGGACT
(SEQ ID NO: 117)		 lCslTslGsdCsdAsdCsdCsdTsdTsdGsdGslAslCslT
(SEQ ID NO: 118)
3260 GCTGCACCTTGGAC
(SEQ ID NO: 119)		 lGslCslTsdGsdCsdAsdCsdCsdTsdTsdGslGslAslC
(SEQ ID NO: 120)
3261 AGCTGCACCTTGGA
(SEQ ID NO: 121)		 lAslGslCsdTsdGsdCsdAsdCsdCsdTsdTslGslGslA
(SEQ ID NO: 122)
4253 CTGCACTGGCCTTG
(SEQ ID NO: 123)		 lCslTslGsdCsdAsdCsdTsdGsdGsdCsdCslTslTslG
(SEQ ID NO: 124)
4254 TCTGCACTGGCCTT
(SEQ ID NO: 125)		 lTslCslTsdGsdCsdAsdCsdTsdGsdGsdCslCslTslT
(SEQ ID NO: 126)
4255 CTCTGCACTGGCCT
(SEQ ID NO: 127)		 lCslTslCsdTsdGsdCsdAsdCsdTsdGsdGslCslCslT
(SEQ ID NO: 128)
4256 TCTCTGCACTGGCC
(SEQ ID NO: 129)		 lTslCslTsdCsdTsdGsdCsdAsdCsdTsdGslGslCslC
(SEQ ID NO: 130)
4257 TTCTCTGCACTGGC
(SEQ ID NO: 131)		 lTslTslCsdTsdCsdTsdGsdCsdAsdCsdTslGslGslC
(SEQ ID NO: 132)
4258 CTTCTCTGCACTGG
(SEQ ID NO: 133)		 lCslTslTsdCsdTsdCsdTsdGsdCsdAsdCslTslGslG
(SEQ ID NO: 134)
4259 GCTTCTCTGCACTG
(SEQ ID NO: 135)		 lGslCslTsdTsdCsdTsdCsdTsdGsdCsdAslCslTslG
(SEQ ID NO: 136)
4260 AGCTTCTCTGCACT
(SEQ ID NO: 137)		 lAslGslCsdTsdTsdCsdTsdCsdTsdGsdCslAslCslT
(SEQ ID NO: 138)
4261 CAGCTTCTCTGCAC
(SEQ ID NO: 139)		 lCslAslGsdCsdTsdTsdCsdTsdCsdTsdGslCslAslC
(SEQ ID NO: 140)
4262 ACAGCTTCTCTGCA
(SEQ ID NO: 141)		 lAslCslAsdGsdCsdTsdTsdCsdTsdCsdTslGslCslA
(SEQ ID NO: 142)
4263 CACAGCTTCTCTGC
(SEQ ID NO: 143)		 lCslAslCsdAsdGsdCsdTsdTsdCsdTsdCslTslGslC
(SEQ ID NO: 144)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 145)		 lTslTslGsdAsdTsdCsdTsdTsdGsdGsdCslCslTslC
(SEQ ID NO: 146)
4318 CTGCAGCTCCTCCA
(SEQ ID NO: 147)		 lCslTslGsdCsdAsdGsdCsdTsdCsdCsdTslCslCslA
(SEQ ID NO: 148)
4717 TGCCTCCTGCAGCC
(SEQ ID NO: 149)		 lTslGslCsdCsdTsdCsdCsdTsdGsdCsdAslGslCslC
(SEQ ID NO: 150)
4773 AGCTTGGCCTTCTC
(SEQ ID NO: 151)		 lAslGslCsdTsdTsdGsdGsdCsdCsdTsdTslCslTslC
(SEQ ID NO: 152)
4904 TCTCCTCCTCCTGC
(SEQ ID NO: 153)		 lTslCslTsdCsdCsdTsdCsdCsdTsdCsdCslTslGslC
(SEQ ID NO: 154)
6099 AGGTTCTTCCTGTC
(SEQ ID NO: 155)		 lAslGslGsdTsdTsdCsdTsdTsdCsdCsdTslGslTslC
(SEQ ID NO: 156)
6101 CCAGGTTCTTCCTG
(SEQ ID NO: 157)		 lCslCslAsdGsdGsdTsdTsdCsdTsdTsdCslCslTslG
(SEQ ID NO: 158)
6102 GCCAGGTTCTTCCT
(SEQ ID NO: 159)		 lGslCslCsdAsdGsdGsdTsdTsdCsdTsdTslCslCslT
(SEQ ID NO: 160)
6103 AGCCAGGTTCTTCC
(SEQ ID NO: 161)		 lAslGslCsdCsdAsdGsdGsdTsdTsdCsdTslTslCslC
(SEQ ID NO: 162)
6104 GAGCCAGGTTCTTC
(SEQ ID NO: 163)		 lGslAslGsdCsdCsdAsdGsdGsdTsdTsdCslTslTslC
(SEQ ID NO: 164)
6142 GACCTTGCTCTGCA
(SEQ ID NO: 165)		 lGslAslCsdCsdTsdTsdGsdCsdTsdCsdTslGslCslA
(SEQ ID NO: 166)
6143 TGACCTTGCTCTGC
(SEQ ID NO: 167)		 lTslGslAsdCsdCsdTsdTsdGsdCsdTsdCslTslGslC
(SEQ ID NO: 168)
6144 TTGACCTTGCTCTG
(SEQ ID NO: 169)		 lTslTslGsdAsdCsdCsdTsdTsdGsdCsdTslCslTslG
(SEQ ID NO: 170)
6146 TCTTGACCTTGCTC
(SEQ ID NO: 171)		 lTslCslTsdTsdGsdAsdCsdCsdTsdTsdGslCslTslC
(SEQ ID NO: 172)
6149 AGCTCTTGACCTTG
(SEQ ID NO: 173)		 lAslGslCsdTsdCsdTsdTsdGsdAsdCsdCslTslTslG
(SEQ ID NO: 174)
6151 GTAGCTCTTGACCT
(SEQ ID NO: 175)		 lGslTslAsdGsdCsdTsdCsdTsdTsdGsdAslCslCslT
(SEQ ID NO: 176)
6220 GTGCTGGGCCTTGC
(SEQ ID NO: 177)		 lGslTslGsdCsdTsdGsdGsdGsdCsdCsdTslTslGslC
(SEQ ID NO: 178)
6273 TTGTTGGCCTGGGT
(SEQ ID NO: 179)		 lTslTslGsdTsdTsdGsdGsdCsdCsdTsdGslGslGslT
(SEQ ID NO: 180)
6277 CAGCTTGTTGGCCT
(SEQ ID NO: 181)		 lCslAslGsdCsdTsdTsdGsdTsdTsdGsdGslCslCslT
(SEQ ID NO: 182)
GTGAATGCGGATGAA
(SEQ ID NO: 1)		 lGslTslGsdAsdAsdTsdGsdCsdGsdGsdAsdTsdGslAslA
(SEQ ID NO: 3)
l = 잠금 뉴클레오티드; d = 데옥시뉴클레오티드; s = 포스포로티오에이트 결합.
SEQ ID NO: 6의 표적 서열의 시작 뉴클레오티드 서열(5'-3') 변형을 가진 서열(5'-3')
513 TCACTCACATCCAT
(SEQ ID NO: 183)		 lTslCslAsmdCsdTsmdCsdAsmdCsdAsdTsmdCslCslAslT
(SEQ ID NO: 184)
514 TTCACTCACATCCA
(SEQ ID NO: 185)		 lTslTslCsdAsmdCsdTsmdCsdAsmdCsdAsdTslCslCslA
(SEQ ID NO: 186)
515 GTTCACTCACATCC
(SEQ ID NO: 187)		 lGslTslTsmdCsdAsmdCsdTsmdCsdAsmdCsdAslTslCslC
(SEQ ID NO: 188)
516 AGTTCACTCACATC
(SEQ ID NO: 189)		 lAslGslTsdTsmdCsdAsmdCsdTsmdCsdAsmdCslAslTslC
(SEQ ID NO: 190)
517 AAGTTCACTCACAT
(SEQ ID NO: 191)		 lAslAslGsdTsdTsmdCsdAsmdCsdTsmdCsdAslCslAslT
(SEQ ID NO: 192)
518 CAAGTTCACTCACA
(SEQ ID NO: 193)		 lCslAslAsdGsdTsdTsmdCsdAsmdCsdTsmdCslAslCslA
(SEQ ID NO: 194)
519 CCAAGTTCACTCAC
(SEQ ID NO: 195)		 lCslCslAsdAsdGsdTsdTsmdCsdAsmdCsdTslCslAslC
(SEQ ID NO: 196)
520 CCCAAGTTCACTCA
(SEQ ID NO: 197)		 lCslCslCsdAsdAsdGsdTsdTsmdCsdAsmdCslTslCslA
(SEQ ID NO: 198)
521 CCCCAAGTTCACTC
(SEQ ID NO: 199)		 lCslCslCsmdCsdAsdAsdGsdTsdTsmdCsdAslCslTslC
(SEQ ID NO: 200)
522 TCCCCAAGTTCACT
(SEQ ID NO: 201)		 lTslCslCsmdCsmdCsdAsdAsdGsdTsdTsmdCslAslCslT
(SEQ ID NO: 202)
523 CTCCCCAAGTTCAC
(SEQ ID NO: 203)		 lCslTslCsmdCsmdCsmdCsdAsdAsdGsdTsdTslCslAslC
(SEQ ID NO: 204)
524 ACTCCCCAAGTTCA
(SEQ ID NO: 205)		 lAslCslTsmdCsmdCsmdCsmdCsdAsdAsdGsdTslTslCslA
(SEQ ID NO: 206)
525 GACTCCCCAAGTTC
(SEQ ID NO: 207)		 lGslAslCsdTsmdCsmdCsmdCsmdCsdAsdAsdGslTslTslC
(SEQ ID NO: 208)
526 AGACTCCCCAAGTT
(SEQ ID NO: 209)		 lAslGslAsmdCsdTsmdCsmdCsmdCsmdCsdAsdAslGslTslT
(SEQ ID NO: 210)
527 CAGACTCCCCAAGT
(SEQ ID NO: 211)		 lCslAslGsdAsmdCsdTsmdCsmdCsmdCsmdCsdAslAslGslT
(SEQ ID NO: 212)
528 GCAGACTCCCCAAG
(SEQ ID NO: 213)		 lGslCslAsdGsdAsmdCsdTsmdCsmdCsmdCsmdCslAslAslG
(SEQ ID NO: 214)
610 AGGCACCCAGACTC
(SEQ ID NO: 215)		 lAslGslGsmdCsdAsmdCsmdCsmdCsdAsdGsdAslCslTslC
(SEQ ID NO: 216)
611 CAGGCACCCAGACT
(SEQ ID NO: 217)		 lCslAslGsdGsmdCsdAsmdCsmdCsmdCsdAsdGslAslCslT
(SEQ ID NO: 218)
612 TCAGGCACCCAGAC
(SEQ ID NO: 219)		 lTslCslAsdGsdGsmdCsdAsmdCsmdCsmdCsdAslGslAslC
(SEQ ID NO: 220)
613 ATCAGGCACCCAGA
(SEQ ID NO: 221)		 lAslTslCsdAsdGsdGsmdCsdAsmdCsmdCsmdCslAslGslA
(SEQ ID NO: 222)
1447 GCTGCAGAAGTGGT
(SEQ ID NO: 223)		 lGslCslTsdGsmdCsdAsdGsdAsdAsdGsdTslGslGslT
(SEQ ID NO: 224)
1518 ATGTCCATGGCATG
(SEQ ID NO: 225)		 lAslTslGsdTsmdCsmdCsdAsdTsdGsdGsmdCslAslTslG
(SEQ ID NO: 226)
1560 ATCTTATAGCAGGC
(SEQ ID NO: 227)		 lAslTslCsdTsdTsdAsdTsdAsdGsmdCsdAslGslGslC
(SEQ ID NO: 228)
1645 ACTCTCAGTGCCAT
(SEQ ID NO: 229)		 lAslCslTsmdCsdTsmdCsdAsdGsdTsdGsmdCslCslAslT
(SEQ ID NO: 230)
1646 CACTCTCAGTGCCA
(SEQ ID NO: 231)		 lCslAslCsdTsmdCsdTsmdCsdAsdGsdTsdGslCslCslA
(SEQ ID NO: 232)
1648 AGCACTCTCAGTGC
(SEQ ID NO: 233)		 lAslGslCsdAsmdCsdTsmdCsdTsmdCsdAsdGslTslGslC
(SEQ ID NO: 234)
1649 CAGCACTCTCAGTG
(SEQ ID NO: 235)		 lCslAslGsmdCsdAsmdCsdTsmdCsdTsmdCsdAslGslTslG
(SEQ ID NO: 236)
1650 TCAGCACTCTCAGT
(SEQ ID NO: 237)		 lTslCslAsdGsmdCsdAsmdCsdTsmdCsdTsmdCslAslGslT
(SEQ ID NO: 238)
1651 GTCAGCACTCTCAG
(SEQ ID NO: 239)		 lGslTslCsdAsdGsmdCsdAsmdCsdTsmdCsdTslCslAslG
(SEQ ID NO: 240)
1652 TGTCAGCACTCTCA
(SEQ ID NO:241 )		 lTslGslTsmdCsdAsdGsmdCsdAsmdCsdTsmdCslTslCslA
(SEQ ID NO: 242)
1655 CCTTGTCAGCACTC
(SEQ ID NO: 243)		 lCslCslTsdTsdGsdTsmdCsdAsdGsmdCsdAslCslTslC
(SEQ ID NO: 244)
1682 CACTGCTGACCCCC
(SEQ ID NO: 245)		 lCslAslCsdTsdGsmdCsdTsdGsdAsmdCsmdCslCslCslC
(SEQ ID NO: 246)
1683 CCACTGCTGACCCC
(SEQ ID NO: 247)		 lCslCslAsmdCsdTsdGsmdCsdTsdGsdAsmdCslCslCslC
(SEQ ID NO: 248)
1684 CCCACTGCTGACCC
(SEQ ID NO: 249)		 lCslCslCsdAsmdCsdTsdGsmdCsdTsdGsdAslCslCslC
(SEQ ID NO: 250)
1685 CCCCACTGCTGACC
(SEQ ID NO: 251)		 lCslCslCsmdCsdAsmdCsdTsdGsmdCsdTsdGslAslCslC
(SEQ ID NO: 252)
1686 TCCCCACTGCTGAC
(SEQ ID NO: 253)		 lTslCslCsmdCsmdCsdAsmdCsdTsdGsmdCsdTslGslAslC
(SEQ ID NO: 254)
1687 GTCCCCACTGCTGA
(SEQ ID NO: 255)		 lGslTslCsmdCsmdCsmdCsdAsmdCsdTsdGsmdCslTslGslA
(SEQ ID NO: 256)
1688 GGTCCCCACTGCTG
(SEQ ID NO: 257)		 lGslGslTsmdCsmdCsmdCsmdCsdAsmdCsdTsdGslCslTslG
(SEQ ID NO: 258)
1689 AGGTCCCCACTGCT
(SEQ ID NO: 259)		 lAslGslGsdTsmdCsmdCsmdCsmdCsdAsmdCsdTslGslCslT
(SEQ ID NO: 260)
1690 GAGGTCCCCACTGC
(SEQ ID NO: 261)		 lGslAslGsdGsdTsmdCsmdCsmdCsmdCsdAsmdCslTslGslC
(SEQ ID NO: 262)
1691 GGAGGTCCCCACTG
(SEQ ID NO: 263)		 lGslGslAsdGsdGsdTsmdCsmdCsmdCsmdCsdAslCslTslG
(SEQ ID NO: 264)
1692 AGGAGGTCCCCACT
(SEQ ID NO: 265)		 lAslGslGsdAsdGsdGsdTsmdCsmdCsmdCsmdCslAslCslT
(SEQ ID NO: 266)
1693 GAGGAGGTCCCCAC
(SEQ ID NO: 267)		 lGslAslGsdGsdAsdGsdGsdTsmdCsmdCsmdCslCslAslC
(SEQ ID NO: 268)
1694 TGAGGAGGTCCCCA
(SEQ ID NO: 269)		 lTslGslAsdGsdGsdAsdGsdGsdTsmdCsmdCslCslCslA
(SEQ ID NO: 270)
1696 TTTGAGGAGGTCCC
(SEQ ID NO: 271)		 lTslTslTsdGsdAsdGsdGsdAsdGsdGsdTslCslCslC
(SEQ ID NO: 272)
1702 AAGGCCTTTGAGGA
(SEQ ID NO: 273)		 lAslAslGsdGsmdCsmdCsdTsdTsdTsdGsdAslGslGslA
(SEQ ID NO: 274)
1773 GCAAACACCACCTG
(SEQ ID NO: 275)		 lGslCslAsdAsdAsmdCsdAsmdCsmdCsdAsmdCslCslTslG
(SEQ ID NO: 276)
1774 AGCAAACACCACCT
(SEQ ID NO: 277)		 lAslGslCsdAsdAsdAsmdCsdAsmdCsmdCsdAslCslCslT
(SEQ ID NO: 278)
1775 CAGCAAACACCACC
(SEQ ID NO:279 )		 lCslAslGsmdCsdAsdAsdAsmdCsdAsmdCsmdCslAslCslC
(SEQ ID NO: 280)
1776 ACAGCAAACACCAC
(SEQ ID NO: 281)		 lAslCslAsdGsmdCsdAsdAsdAsmdCsdAsmdCslCslAslC
(SEQ ID NO: 282)
1828 AGACACCAGCCACC
(SEQ ID NO: 283)		 lAslGslAsmdCsdAsmdCsmdCsdAsdGsmdCsmdCslAslCslC
(SEQ ID NO: 284)
1829 GAGACACCAGCCAC
(SEQ ID NO: 285)		 lGslAslGsdAsmdCsdAsmdCsmdCsdAsdGsmdCslCslAslC
(SEQ ID NO: 286)
2218 CTTCTTGTCAGGCC
(SEQ ID NO: 287)		 lCslTslTsmdCsdTsdTsdGsdTsmdCsdAsdGslGslCslC
(SEQ ID NO: 288)
2238 AAGTGGGCCTGGTA
(SEQ ID NO: 289)		 lAslAslGsdTsdGsdGsdGsmdCsmdCsdTsdGslGslTslA
(SEQ ID NO: 290)
2254 GTAGTGGACCACCT
(SEQ ID NO: 291)		 lGslTslAsdGsdTsdGsdGsdAsmdCsmdCsdAslCslCslT
(SEQ ID NO: 292)
2574 GCATCCATGACCCC
(SEQ ID NO: 293)		 lGslCslAsdTsmdCsmdCsdAsdTsdGsdAsmdCslCslCslC
(SEQ ID NO: 294)
2575 GGCATCCATGACCC
(SEQ ID NO: 295)		 lGslGslCsdAsdTsmdCsmdCsdAsdTsdGsdAslCslCslC
(SEQ ID NO: 296)
2576 AGGCATCCATGACC
(SEQ ID NO: 297)		 lAslGslGsmdCsdAsdTsmdCsmdCsdAsdTsdGslAslCslC
(SEQ ID NO: 298)
2577 AAGGCATCCATGAC
(SEQ ID NO: 299)		 lAslAslGsdGsmdCsdAsdTsmdCsmdCsdAsdTslGslAslC
(SEQ ID NO: 300)
4281 TGATCCTCATAGGT
(SEQ ID NO: 301)		 lTslGslAsdTsmdCsmdCsdTsmdCsdAsdTsdAslGslGslT
(SEQ ID NO: 302)
4282 CTGATCCTCATAGG
(SEQ ID NO: 303)		 lCslTslGsdAsdTsmdCsmdCsdTsmdCsdAsdTslAslGslG
(SEQ ID NO: 304)
4283 GCTGATCCTCATAG
(SEQ ID NO: 305)		 lGslCslTsdGsdAsdTsmdCsmdCsdTsmdCsdAslTslAslG
(SEQ ID NO: 306)
4284 AGCTGATCCTCATA
(SEQ ID NO: 307)		 lAslGslCsdTsdGsdAsdTsmdCsmdCsdTsmdCslAslTslA
(SEQ ID NO: 308)
4305 ACCTTGATCTTGGC
(SEQ ID NO: 309)		 lAslCslCsdTsdTsdGsdAsdTsmdCsdTsdTslGslGslC
(SEQ ID NO: 310)
4656 ATGGCATCTGCTTC
(SEQ ID NO: 311)		 lAslTslGsdGsmdCsdAsdTsmdCsdTsdGsmdCslTslTslC
(SEQ ID NO: 312)
4657 GATGGCATCTGCTT
(SEQ ID NO: 313)		 lGslAslTsdGsdGsmdCsdAsdTsmdCsdTsdGslCslTslT
(SEQ ID NO: 314)
4661 TCTGGATGGCATCT
(SEQ ID NO: 315)		 lTslCslTsdGsdGsdAsdTsdGsdGsmdCsdAslTslCslT
(SEQ ID NO: 316)
6141 ACCTTGCTCTGCAG
(SEQ ID NO: 317)		 lAslCslCsdTsdTsdGsmdCsdTsmdCsdTsdGslCslAslG
(SEQ ID NO: 318)
436 AGGCAGCAGGCACT
(SEQ ID NO: 319)		 lAslGslGsmdCsdAsdGsmdCsdAsdGsdGsmdCslAslCslT
(SEQ ID NO: 320)
437 AAGGCAGCAGGCAC
(SEQ ID NO: 321)		 lAslAslGsdGsmdCsdAsdGsmdCsdAsdGsdGslCslAslC
(SEQ ID NO: 322)
438 CAAGGCAGCAGGCA
(SEQ ID NO: 323)		 lCslAslAsdGsdGsmdCsdAsdGsmdCsdAsdGslGslCslA
(SEQ ID NO: 324)
439 CCAAGGCAGCAGGC
(SEQ ID NO: 325)		 lCslCslAsdAsdGsdGsmdCsdAsdGsmdCsdAslGslGslC
(SEQ ID NO: 326)
482 GGTGAAGGAGGAGG
(SEQ ID NO: 327)		 lGslGslTsdGsdAsdAsdGsdGsdAsdGsdGslAslGslG
(SEQ ID NO: 328)
483 GGGTGAAGGAGGAG
(SEQ ID NO: 329)		 lGslGslGsdTsdGsdAsdAsdGsdGsdAsdGslGslAslG
(SEQ ID NO: 330)
509 TCACATCCATCATG
(SEQ ID NO: 331)		 lTslCslAsmdCsdAsdTsmdCsmdCsdAsdTsmdCslAslTslG
(SEQ ID NO: 332)
511 ACTCACATCCATCA
(SEQ ID NO: 333)		 lAslCslTsmdCsdAsmdCsdAsdTsmdCsmdCsdAslTslCslA
(SEQ ID NO: 334)
512 CACTCACATCCATC
(SEQ ID NO: 335)		 lCslAslCsdTsmdCsdAsmdCsdAsdTsmdCsmdCslAslTslC
(SEQ ID NO: 336)
616 TTCATCAGGCACCC
(SEQ ID NO: 337)		 lTslTslCsdAsdTsmdCsdAsdGsdGsmdCsdAslCslCslC
(SEQ ID NO: 338)
617 GTTCATCAGGCACC
(SEQ ID NO: 339)		 lGslTslTsmdCsdAsdTsmdCsdAsdGsdGsmdCslAslCslC
(SEQ ID NO: 340)
622 GTCCTGTTCATCAG
(SEQ ID NO: 341)		 lGslTslCsmdCsdTsdGsdTsdTsmdCsdAsdTslCslAslG
(SEQ ID NO: 342)
690 TGGTCTTTGGTCTC
(SEQ ID NO: 343)		 lTslGslGsdTsmdCsdTsdTsdTsdGsdGsdTslCslTslC
(SEQ ID NO: 344)
804 TTGTGCAGCACAGA
(SEQ ID NO: 345)		 lTslTslGsdTsdGsmdCsdAsdGsmdCsdAsmdCslAslGslA
(SEQ ID NO: 346)
805 GTTGTGCAGCACAG
(SEQ ID NO: 347)		 lGslTslTsdGsdTsdGsmdCsdAsdGsmdCsdAslCslAslG
(SEQ ID NO: 348)
892 GACTGGGAGCCATT
(SEQ ID NO: 349)		 lGslAslCsdTsdGsdGsdGsdAsdGsmdCsmdCslAslTslT
(SEQ ID NO: 350)
893 AGACTGGGAGCCAT
(SEQ ID NO: 351)		 lAslGslAsmdCsdTsdGsdGsdGsdAsdGsmdCslCslAslT
(SEQ ID NO: 352)
1102 GTCTCCCAGGGCAG
(SEQ ID NO: 353)		 lGslTslCsdTsmdCsmdCsmdCsdAsdGsdGsdGslCslAslG
(SEQ ID NO: 354)
1215 CTCAGGGTCTTGGC
(SEQ ID NO: 355)		 lCslTslCsdAsdGsdGsdGsdTsmdCsdTsdTslGslGslC
(SEQ ID NO: 356)
1216 CCTCAGGGTCTTGG
(SEQ ID NO: 357)		 lCslCslTsmdCsdAsdGsdGsdGsdTsmdCsdTslTslGslG
(SEQ ID NO: 358)
1217 TCCTCAGGGTCTTG
(SEQ ID NO: 359)		 lTslCslCsdTsmdCsdAsdGsdGsdGsdTsmdCslTslTslG
(SEQ ID NO: 360)
1219 ATTCCTCAGGGTCT
(SEQ ID NO: 361)		 lAslTslTsmdCsmdCsdTsmdCsdAsdGsdGsdGslTslCslT
(SEQ ID NO: 362)
1220 CATTCCTCAGGGTC
(SEQ ID NO: 363)		 lCslAslTsdTsmdCsmdCsdTsmdCsdAsdGsdGslGslTslC
(SEQ ID NO: 364)
1222 ATCATTCCTCAGGG
(SEQ ID NO: 365)		 lAslTslCsdAsdTsdTsmdCsmdCsdTsmdCsdAslGslGslG
(SEQ ID NO: 366)
1225 GTTATCATTCCTCA
(SEQ ID NO: 366)		 lGslTslTsdAsdTsmdCsdAsdTsdTsmdCsmdCslTslCslA
(SEQ ID NO: 368)
1226 AGTTATCATTCCTC
(SEQ ID NO: 369)		 lAslGslTsdTsdAsdTsmdCsdAsdTsdTsmdCslCslTslC
(SEQ ID NO: 370)
1268 AGGGACCAAAGTGA
(SEQ ID NO: 371)		 lAslGslGsdGsdAsmdCsmdCsdAsdAsdAsdGslTslGslA
(SEQ ID NO: 372)
1273 CCCAGAGGGACCAA
(SEQ ID NO: 373)		 lCslCslCsdAsdGsdAsdGsdGsdGsdAsmdCslCslAslA
(SEQ ID NO: 374)
1274 TCCCAGAGGGACCA
(SEQ ID NO: 375)		 lTslCslCsmdCsdAsdGsdAsdGsdGsdGsdAslCslCslA
(SEQ ID NO: 376)
1275 TTCCCAGAGGGACC
(SEQ ID NO: 377)		 lTslTslCsmdCsmdCsdAsdGsdAsdGsdGsdGslAslCslC
(SEQ ID NO: 378)
1276 CTTCCCAGAGGGAC
(SEQ ID NO: 379)		 lCslTslTsmdCsmdCsmdCsdAsdGsdAsdGsdGslGslAslC
(SEQ ID NO: 380)
1277 GCTTCCCAGAGGGA
(SEQ ID NO: 381)		 lGslCslTsdTsmdCsmdCsmdCsdAsdGsdAsdGslGslGslA
(SEQ ID NO: 382)
1301 AGCTGTCAATATCC
(SEQ ID NO: 383)		 lAslGslCsdTsdGsdTsmdCsdAsdAsdTsdAslTslCslC
(SEQ ID NO: 384)
1302 TAGCTGTCAATATC
(SEQ ID NO: 385)		 lTslAslGsmdCsdTsdGsdTsmdCsdAsdAsdTslAslTslC
(SEQ ID NO: 386)
1303 ATAGCTGTCAATAT
(SEQ ID NO: 387)		 lAslTslAsdGsmdCsdTsdGsdTsmdCsdAsdAslTslAslT
(SEQ ID NO: 388)
1304 GATAGCTGTCAATA
(SEQ ID NO: 389)		 lGslAslTsdAsdGsmdCsdTsdGsdTsmdCsdAslAslTslA
(SEQ ID NO: 390)
1379 CTGAGAGGATCTGG
(SEQ ID NO: 391)		 lCslTslGsdAsdGsdAsdGsdGsdAsdTsmdCslTslGslG
(SEQ ID NO: 392)
1380 CCTGAGAGGATCTG
(SEQ ID NO: 393)		 lCslCslTsdGsdAsdGsdAsdGsdGsdAsdTslCslTslG
(SEQ ID NO: 394)
1417 AGACAGAAGCAGCA
(SEQ ID NO: 395)		 lAslGslAsmdCsdAsdGsdAsdAsdGsmdCsdAslGslCslA
(SEQ ID NO: 396)
1418 TAGACAGAAGCAGC
(SEQ ID NO: 397)		 lTslAslGsdAsmdCsdAsdGsdAsdAsdGsmdCslAslGslC
(SEQ ID NO: 398)
1419 ATAGACAGAAGCAG
(SEQ ID NO: 399)		 lAslTslAsdGsdAsmdCsdAsdGsdAsdAsdGslCslAslG
(SEQ ID NO: 400)
1420 CATAGACAGAAGCA
(SEQ ID NO: 401)		 lCslAslTsdAsdGsdAsmdCsdAsdGsdAsdAslGslCslA
(SEQ ID NO: 402)
1421 TCATAGACAGAAGC
(SEQ ID NO: 403)		 lTslCslAsdTsdAsdGsdAsmdCsdAsdGsdAslAslGslC
(SEQ ID NO: 404)
1422 TTCATAGACAGAAG
(SEQ ID NO: 405)		 lTslTslCsdAsdTsdAsdGsdAsmdCsdAsdGslAslAslG
(SEQ ID NO: 406)
1423 GTTCATAGACAGAA
(SEQ ID NO: 407)		 lGslTslTsmdCsdAsdTsdAsdGsdAsmdCsdAslGslAslA
(SEQ ID NO: 408)
1424 GGTTCATAGACAGA
(SEQ ID NO: 409)		 lGslGslTsdTsmdCsdAsdTsdAsdGsdAsmdCslAslGslA
(SEQ ID NO: 410)
1425 GGGTTCATAGACAG
(SEQ ID NO: 411)		 lGslGslGsdTsdTsmdCsdAsdTsdAsdGsdAslCslAslG
(SEQ ID NO: 412)
1484 CCCCATCATTCATG
(SEQ ID NO: 413)		 lCslCslCsmdCsdAsdTsmdCsdAsdTsdTsmdCslAslTslG
(SEQ ID NO: 414)
1557 TTATAGCAGGCACA
(SEQ ID NO: 415)		 lTslTslAsdTsdAsdGsmdCsdAsdGsdGsmdCslAslCslA
(SEQ ID NO: 416)
1558 CTTATAGCAGGCAC
(SEQ ID NO: 417)		 lCslTslTsdAsdTsdAsdGsmdCsdAsdGsdGslCslAslC
(SEQ ID NO: 418)
1559 TCTTATAGCAGGCA
(SEQ ID NO: 419)		 lTslCslTsdTsdAsdTsdAsdGsmdCsdAsdGslGslCslA
(SEQ ID NO: 420)
1561 GATCTTATAGCAGG
(SEQ ID NO: 421)		 lGslAslTsmdCsdTsdTsdAsdTsdAsdGsmdCslAslGslG
(SEQ ID NO: 422)
1582 AAAGTGCAGGAGGG
(SEQ ID NO: 423)		 lAslAslAsdGsdTsdGsmdCsdAsdGsdGsdAslGslGslG
(SEQ ID NO: 424)
1587 TTGCCAAAGTGCAG
(SEQ ID NO: 425)		 lTslTslGsmdCsmdCsdAsdAsdAsdGsdTsdGslCslAslG
(SEQ ID NO: 426)
1703 AAAGGCCTTTGAGG
(SEQ ID NO: 427)		 lAslAslAsdGsdGsmdCsmdCsdTsdTsdTsdGslAslGslG
(SEQ ID NO: 428)
1704 AAAAGGCCTTTGAG
(SEQ ID NO: 429)		 lAslAslAsdAsdGsdGsmdCsmdCsdTsdTsdTslGslAslG
(SEQ ID NO: 430)
1705 CAAAAGGCCTTTGA
(SEQ ID NO: 431)		 lCslAslAsdAsdAsdGsdGsmdCsmdCsdTsdTslTslGslA
(SEQ ID NO: 432)
1706 GCAAAAGGCCTTTG
(SEQ ID NO: 433)		 lGslCslAsdAsdAsdAsdGsdGsmdCsmdCsdTslTslTslG
(SEQ ID NO: 434)
1707 TGCAAAAGGCCTTT
(SEQ ID NO: 435)		 lTslGslCsdAsdAsdAsdAsdGsdGsmdCsmdCslTslTslT
(SEQ ID NO: 436)
1708 GTGCAAAAGGCCTT
(SEQ ID NO: 437)		 lGslTslGsmdCsdAsdAsdAsdAsdGsdGsmdCslCslTslT
(SEQ ID NO: 438)
1709 GGTGCAAAAGGCCT
(SEQ ID NO: 439)		 lGslGslTsdGsmdCsdAsdAsdAsdAsdGsdGslCslCslT
(SEQ ID NO: 440)
1710 GGGTGCAAAAGGCC
(SEQ ID NO: 441)		 lGslGslGsdTsdGsmdCsdAsdAsdAsdAsdGslGslCslC
(SEQ ID NO: 442)
1804 GTCATAGGTGGCCT
(SEQ ID NO: 443)		 lGslTslCsdAsdTsdAsdGsdGsdTsdGsdGslCslCslT
(SEQ ID NO: 444)
1805 GGTCATAGGTGGCC
(SEQ ID NO: 445)		 lGslGslTsmdCsdAsdTsdAsdGsdGsdTsdGslGslCslC
(SEQ ID NO: 446)
1819 CCACCTGAACAGCC
(SEQ ID NO: 447)		 lCslCslAsmdCsmdCsdTsdGsdAsdAsmdCsdAslGslCslC
(SEQ ID NO: 448)
1820 GCCACCTGAACAGC
(SEQ ID NO: 449)		 lGslCslCsdAsmdCsmdCsdTsdGsdAsdAsmdCslAslGslC
(SEQ ID NO: 450)
1827 GACACCAGCCACCT
(SEQ ID NO: 451)		 lGslAslCsdAsmdCsmdCsdAsdGsmdCsmdCsdAslCslCslT
(SEQ ID NO: 452)
1850 TGTCCAGGGTCTGG
(SEQ ID NO: 453)		 lTslGslTsmdCsmdCsdAsdGsdGsdGsdTsmdCslTslGslG
(SEQ ID NO: 454)
1851 GTGTCCAGGGTCTG
(SEQ ID NO: 455)		 lGslTslGsdTsmdCsmdCsdAsdGsdGsdGsdTslCslTslG
(SEQ ID NO: 456)
1852 TGTGTCCAGGGTCT
(SEQ ID NO: 457)		 lTslGslTsdGsdTsmdCsmdCsdAsdGsdGsdGslTslCslT
(SEQ ID NO: 458)
2189 TGGGTGACTTCCCC
(SEQ ID NO: 459)		 lTslGslGsdGsdTsdGsdAsmdCsdTsdTsmdCslCslCslC
(SEQ ID NO: 460)
2190 TTGGGTGACTTCCC
(SEQ ID NO: 461)		 lTslTslGsdGsdGsdTsdGsdAsmdCsdTsdTslCslCslC
(SEQ ID NO: 462)
2191 ATTGGGTGACTTCC
(SEQ ID NO: 463)		 lAslTslTsdGsdGsdGsdTsdGsdAsmdCsdTslTslCslC
(SEQ ID NO: 464)
2198 GCTGGAAATTGGGT
(SEQ ID NO: 465)		 lGslCslTsdGsdGsdAsdAsdAsdTsdTsdGslGslGslT
(SEQ ID NO: 466)
2274 CTGTAAGGCACCAC
(SEQ ID NO: 467)		 lCslTslGsdTsdAsdAsdGsdGsmdCsdAsmdCslCslAslC
(SEQ ID NO: 468)
2275 GCTGTAAGGCACCA
(SEQ ID NO: 469)		 lGslCslTsdGsdTsdAsdAsdGsdGsmdCsdAslCslCslA
(SEQ ID NO: 470)
2276 TGCTGTAAGGCACC
(SEQ ID NO: 471)		 lTslGslCsdTsdGsdTsdAsdAsdGsdGsmdCslAslCslC
(SEQ ID NO: 472)
2350 ATTCTGTGACTTCT
(SEQ ID NO: 473)		 lAslTslTsmdCsdTsdGsdTsdGsdAsmdCsdTslTslCslT
(SEQ ID NO: 474)
2351 TATTCTGTGACTTC
(SEQ ID NO: 475)		 lTslAslTsdTsmdCsdTsdGsdTsdGsdAsmdCslTslTslC
(SEQ ID NO: 476)
2352 CTATTCTGTGACTT
(SEQ ID NO: 477)		 lCslTslAsdTsdTsmdCsdTsdGsdTsdGsdAslCslTslT
(SEQ ID NO: 478)
2353 CCTATTCTGTGACT
(SEQ ID NO: 479)		 lCslCslTsdAsdTsdTsmdCsdTsdGsdTsdGslAslCslT
(SEQ ID NO: 480)
2354 GCCTATTCTGTGAC
(SEQ ID NO: 481)		 lGslCslCsdTsdAsdTsdTsmdCsdTsdGsdTslGslAslC
(SEQ ID NO: 482)
2355 AGCCTATTCTGTGA
(SEQ ID NO: 483)		 lAslGslCsmdCsdTsdAsdTsdTsmdCsdTsdGslTslGslA
(SEQ ID NO: 484)
2356 GAGCCTATTCTGTG
(SEQ ID NO: 485)		 lGslAslGsmdCsmdCsdTsdAsdTsdTsmdCsdTslGslTslG
(SEQ ID NO: 486)
2357 GGAGCCTATTCTGT
(SEQ ID NO: 487)		 lGslGslAsdGsmdCsmdCsdTsdAsdTsdTsmdCslTslGslT
(SEQ ID NO: 488)
2358 AGGAGCCTATTCTG
(SEQ ID NO: 489)		 lAslGslGsdAsdGsmdCsmdCsdTsdAsdTsdTslCslTslG
(SEQ ID NO: 490)
2359 CAGGAGCCTATTCT
(SEQ ID NO: 491)		 lCslAslGsdGsdAsdGsmdCsmdCsdTsdAsdTslTslCslT
(SEQ ID NO: 492)
2360 CCAGGAGCCTATTC
(SEQ ID NO: 493)		 lCslCslAsdGsdGsdAsdGsmdCsmdCsdTsdAslTslTslC
(SEQ ID NO: 494)
2361 GCCAGGAGCCTATT
(SEQ ID NO: 495)		 lGslCslCsdAsdGsdGsdAsdGsmdCsmdCsdTslAslTslT
(SEQ ID NO: 496)
2375 TCTCATAGAGAGTC
(SEQ ID NO: 497)		 lTslCslTsmdCsdAsdTsdAsdGsdAsdGsdAslGslTslC
(SEQ ID NO: 498)
2376 TTCTCATAGAGAGT
(SEQ ID NO: 499)		 lTslTslCsdTsmdCsdAsdTsdAsdGsdAsdGslAslGslT
(SEQ ID NO: 500)
2396 TGGAGCAGGAGCCC
(SEQ ID NO: 501)		 lTslGslGsdAsdGsmdCsdAsdGsdGsdAsdGslCslCslC
(SEQ ID NO: 502)
2397 GTGGAGCAGGAGCC
(SEQ ID NO: 503)		 lGslTslGsdGsdAsdGsmdCsdAsdGsdGsdAslGslCslC
(SEQ ID NO: 504)
2443 TGCTGCCTTCTTAC
(SEQ ID NO: 505)		 lTslGslCsdTsdGsmdCsmdCsdTsdTsmdCsdTslTslAslC
(SEQ ID NO: 506)
2444 ATGCTGCCTTCTTA
(SEQ ID NO: 507)		 lAslTslGsmdCsdTsdGsmdCsmdCsdTsdTsmdCslTslTslA
(SEQ ID NO: 508)
2445 GATGCTGCCTTCTT
(SEQ ID NO: 509)		 lGslAslTsdGsmdCsdTsdGsmdCsmdCsdTsdTslCslTslT
(SEQ ID NO: 510)
2579 AGAAGGCATCCATG
(SEQ ID NO: 511)		 lAslGslAsdAsdGsdGsmdCsdAsdTsmdCsmdCslAslTslG
(SEQ ID NO: 512)
2580 AAGAAGGCATCCAT
(SEQ ID NO: 513)		 lAslAslGsdAsdAsdGsdGsmdCsdAsdTsmdCslCslAslT
(SEQ ID NO: 514)
2581 CAAGAAGGCATCCA
(SEQ ID NO: 515)		 lCslAslAsdGsdAsdAsdGsdGsmdCsdAsdTslCslCslA
(SEQ ID NO: 516)
2584 CACCAAGAAGGCAT
(SEQ ID NO: 517)		 lCslAslCsmdCsdAsdAsdGsdAsdAsdGsdGslCslAslT
(SEQ ID NO: 518)
2585 GCACCAAGAAGGCA
(SEQ ID NO: 519)		 lGslCslAsmdCsmdCsdAsdAsdGsdAsdAsdGslGslCslA
(SEQ ID NO: 520)
2587 TAGCACCAAGAAGG
(SEQ ID NO: 521)		 lTslAslGsmdCsdAsmdCsmdCsdAsdAsdGsdAslAslGslG
(SEQ ID NO: 522)
2588 GTAGCACCAAGAAG
(SEQ ID NO: 523)		 lGslTslAsdGsmdCsdAsmdCsmdCsdAsdAsdGslAslAslG
(SEQ ID NO: 524)
2589 TGTAGCACCAAGAA (SEQ ID NO: 525) lTslGslTsdAsdGsmdCsdAsmdCsmdCsdAsdAslGslAslA
(SEQ ID NO: 526)
2590 GTGTAGCACCAAGA
(SEQ ID NO: 527)		 lGslTslGsdTsdAsdGsmdCsdAsmdCsmdCsdAslAslGslA
(SEQ ID NO: 528)
2591 GGTGTAGCACCAAG
(SEQ ID NO: 529)		 lGslGslTsdGsdTsdAsdGsmdCsdAsmdCsmdCslAslAslG (SEQ ID NO: 530)
2592 TGGTGTAGCACCAA
(SEQ ID NO: 531)		 lTslGslGsdTsdGsdTsdAsdGsmdCsdAsmdCslCslAslA
(SEQ ID NO: 532)
2709 GGGATGGCACTGGG
(SEQ ID NO: 533)		 lGslGslGsdAsdTsdGsdGsmdCsdAsmdCsdTslGslGslG
(SEQ ID NO: 534)
2731 GCTGTCCATGAAGG
(SEQ ID NO: 535)		 lGslCslTsdGsdTsmdCsmdCsdAsdTsdGsdAslAslGslG
(SEQ ID NO: 536)
2830 GCCTAGAAGCCCAG
(SEQ ID NO: 537)		 lGslCslCsdTsdAsdGsdAsdAsdGsmdCsmdCslCslAslG
(SEQ ID NO: 538)
2986 GGCATTGAAGGCAC
(SEQ ID NO: 539)		 lGslGslCsdAsdTsdTsdGsdAsdAsdGsdGslCslAslC
(SEQ ID NO: 540)
3248 ACTTGATCAGCAAG
(SEQ ID NO: 541)		 lAslCslTsdTsdGsdAsdTsmdCsdAsdGsmdCslAslAslG
(SEQ ID NO: 542)
3249 GACTTGATCAGCAA
(SEQ ID NO: 543)		 lGslAslCsdTsdTsdGsdAsdTsmdCsdAsdGslCslAslA
(SEQ ID NO: 544)
3625 GCATTCCAGGTCCT
(SEQ ID NO: 545)		 lGslCslAsdTsdTsmdCsmdCsdAsdGsdGsdTslCslCslT
(SEQ ID NO: 546)
3626 AGCATTCCAGGTCC
(SEQ ID NO: 547)		 lAslGslCsdAsdTsdTsmdCsmdCsdAsdGsdGslTslCslC
(SEQ ID NO: 548)
3628 GGAGCATTCCAGGT
(SEQ ID NO: 549)		 lGslGslAsdGsmdCsdAsdTsdTsmdCsmdCsdAslGslGslT
(SEQ ID NO: 550)
3629 GGGAGCATTCCAGG
(SEQ ID NO: 551)		 lGslGslGsdAsdGsmdCsdAsdTsdTsmdCsmdCslAslGslG
(SEQ ID NO: 552)
3631 CAGGGAGCATTCCA
(SEQ ID NO: 553)		 lCslAslGsdGsdGsdAsdGsmdCsdAsdTsdTslCslCslA
(SEQ ID NO: 554)
3793 CAGGCTCAGCTGGC
(SEQ ID NO: 555)		 lCslAslGsdGsmdCsdTsmdCsdAsdGsmdCsdTslGslGslC
(SEQ ID NO: 556)
3794 GCAGGCTCAGCTGG
(SEQ ID NO: 557)		 lGslCslAsdGsdGsmdCsdTsmdCsdAsdGsmdCslTslGslG
(SEQ ID NO: 558)
4233 GTCAGAGTCTCCAC
(SEQ ID NO: 559)		 lGslTslCsdAsdGsdAsdGsdTsmdCsdTsmdCslCslAslC
(SEQ ID NO: 560)
4234 GGTCAGAGTCTCCA
(SEQ ID NO: 561)		 lGslGslTsmdCsdAsdGsdAsdGsdTsmdCsdTslCslCslA
(SEQ ID NO: 562)
4235 GGGTCAGAGTCTCC
(SEQ ID NO: 563)		 lGslGslGsdTsmdCsdAsdGsdAsdGsdTsmdCslTslCslC
(SEQ ID NO: 564)
4286 TTAGCTGATCCTCA
(SEQ ID NO: 565)		 lTslTslAsdGsmdCsdTsdGsdAsdTsmdCsmdCslTslCslA
(SEQ ID NO: 566)
4287 CTTAGCTGATCCTC
(SEQ ID NO: 567)		 lCslTslTsdAsdGsmdCsdTsdGsdAsdTsmdCslCslTslC
(SEQ ID NO: 568)
4410 ATCAGACACTCCTT
(SEQ ID NO: 569)		 lAslTslCsdAsdGsdAsmdCsdAsmdCsdTsmdCslCslTslT
(SEQ ID NO: 570)
4412 TGATCAGACACTCC
(SEQ ID NO: 571)		 lTslGslAsdTsmdCsdAsdGsdAsmdCsdAsmdCslTslCslC
(SEQ ID NO: 572)
4413 CTGATCAGACACTC
(SEQ ID NO: 573)		 lCslTslGsdAsdTsmdCsdAsdGsdAsmdCsdAslCslTslC
(SEQ ID NO: 574)
4414 ACTGATCAGACACT
(SEQ ID NO: 575)		 lAslCslTsdGsdAsdTsmdCsdAsdGsdAsmdCslAslCslT
(SEQ ID NO: 576)
4415 GACTGATCAGACAC
(SEQ ID NO: 577)		 lGslAslCsdTsdGsdAsdTsmdCsdAsdGsdAslCslAslC
(SEQ ID NO: 578)
4416 TGACTGATCAGACA
(SEQ ID NO: 579)		 lTslGslAsmdCsdTsdGsdAsdTsmdCsdAsdGslAslCslA
(SEQ ID NO: 580)
4417 CTGACTGATCAGAC
(SEQ ID NO: 581)		 lCslTslGsdAsmdCsdTsdGsdAsdTsmdCsdAslGslAslC
(SEQ ID NO: 582)
4418 GCTGACTGATCAGA
(SEQ ID NO: 583)		 lGslCslTsdGsdAsmdCsdTsdGsdAsdTsmdCslAslGslA
(SEQ ID NO: 584)
4419 AGCTGACTGATCAG
(SEQ ID NO: 585)		 lAslGslCsdTsdGsdAsmdCsdTsdGsdAsdTslCslAslG
(SEQ ID NO: 586)
4422 CTCAGCTGACTGAT
(SEQ ID NO: 587)		 lCslTslCsdAsdGsmdCsdTsdGsdAsmdCsdTslGslAslT
(SEQ ID NO: 588)
4423 GCTCAGCTGACTGA
(SEQ ID NO: 589)		 lGslCslTsmdCsdAsdGsmdCsdTsdGsdAsmdCslTslGslA
(SEQ ID NO: 590)
4424 GGCTCAGCTGACTG
(SEQ ID NO: 591)		 lGslGslCsdTsmdCsdAsdGsmdCsdTsdGsdAslCslTslG
(SEQ ID NO: 592)
4797 TCCTCTGACTCTGT
(SEQ ID NO: 593)		 lTslCslCsdTsmdCsdTsdGsdAsmdCsdTsmdCslTslGslT
(SEQ ID NO: 594)
4798 ATCCTCTGACTCTG
(SEQ ID NO: 595)		 lAslTslCsmdCsdTsmdCsdTsdGsdAsmdCsdTslCslTslG
(SEQ ID NO: 596)
4799 CATCCTCTGACTCT
(SEQ ID NO: 597)		 lCslAslTsmdCsmdCsdTsmdCsdTsdGsdAsmdCslTslCslT
(SEQ ID NO: 598)
4800 ACATCCTCTGACTC
(SEQ ID NO: 599)		 lAslCslAsdTsmdCsmdCsdTsmdCsdTsdGsdAslCslTslC
(SEQ ID NO: 600)
4801 TACATCCTCTGACT
(SEQ ID NO: 601)		 lTslAslCsdAsdTsmdCsmdCsdTsmdCsdTsdGslAslCslT
(SEQ ID NO: 602)
4802 TTACATCCTCTGAC
(SEQ ID NO: 603)		 lTslTslAsmdCsdAsdTsmdCsmdCsdTsmdCsdTslGslAslC
(SEQ ID NO: 604)
4803 GTTACATCCTCTGA
(SEQ ID NO: 605)		 lGslTslTsdAsmdCsdAsdTsmdCsmdCsdTsmdCslTslGslA
(SEQ ID NO: 606)
4804 GGTTACATCCTCTG
(SEQ ID NO: 607)		 lGslGslTsdTsdAsmdCsdAsdTsmdCsmdCsdTslCslTslG
(SEQ ID NO: 608)
4805 GGGTTACATCCTCT
(SEQ ID NO: 609)		 lGslGslGsdTsdTsdAsmdCsdAsdTsmdCsmdCslTslCslT
(SEQ ID NO: 610)
4806 AGGGTTACATCCTC
(SEQ ID NO: 611)		 lAslGslGsdGsdTsdTsdAsmdCsdAsdTsmdCslCslTslC
(SEQ ID NO: 612)
4807 CAGGGTTACATCCT
(SEQ ID NO: 613)		 lCslAslGsdGsdGsdTsdTsdAsmdCsdAsdTslCslCslT
(SEQ ID NO: 614)
4808 CCAGGGTTACATCC
(SEQ ID NO: 615)		 lCslCslAsdGsdGsdGsdTsdTsdAsmdCsdAslTslCslC
(SEQ ID NO: 616)
4811 GCTCCAGGGTTACA
(SEQ ID NO: 617)		 lGslCslTsmdCsmdCsdAsdGsdGsdGsdTsdTslAslCslA
(SEQ ID NO: 618)
4812 AGCTCCAGGGTTAC
(SEQ ID NO: 619)		 lAslGslCsdTsmdCsmdCsdAsdGsdGsdGsdTslTslAslC
(SEQ ID NO: 620)
4836 GCAGCTGCTGAGGT
(SEQ ID NO: 621)		 lGslCslAsdGsmdCsdTsdGsmdCsdTsdGsdAslGslGslT
(SEQ ID NO: 622)
4837 AGCAGCTGCTGAGG
(SEQ ID NO: 623)		 lAslGslCsdAsdGsmdCsdTsdGsmdCsdTsdGslAslGslG
(SEQ ID NO: 624)
6033 CCCTTAAGGGCCTC
(SEQ ID NO: 625)		 lCslCslCsdTsdTsdAsdAsdGsdGsdGsmdCslCslTslC
(SEQ ID NO: 626)
l = 잠금 뉴클레오티드; d = 데옥시뉴클레오티드; mdC = 5-메틸 시토신; m = 2'-O-메틸 뉴클레오티드; s = 포스포로티오에이트 결합
SEQ ID NO: 6의 표적 서열의 시작 뉴클레오티드 서열(5'-3') 변형을 가진 서열(5'-3')
436 AGGCAGCAGGCACT
(SEQ ID NO: 627)		 lAsdGslGsdCslAslGsdCsdAslGsdGslCsdAslCslT
(SEQ ID NO: 628)
513 TCACTCACATCCAT
(SEQ ID NO: 629)		 lTsdCslAsdCslTslCsdAsdCslAsdTslCsdCslAslT
(SEQ ID NO: 630)
524 ACTCCCCAAGTTCA
(SEQ ID NO: 631)		 lAsdCslTsdCslCslCsdCsdAslAsdGslTsdTslCslA
(SEQ ID NO: 632)
610 AGGCACCCAGACTC
(SEQ ID NO: 633)		 lAsdGslGsdCslAslCsdCsdCslAsdGslAsdCslTslC
(SEQ ID NO: 634)
735 GGGTTCATGGGCTG
(SEQ ID NO: 635)		 lGsdGslGsdTslTslCsdAsdTslGsdGslGsdCslTslG
(SEQ ID NO: 636)
867 ATGGTGACACAGAA
(SEQ ID NO: 637)		 lAsdTslGsdGslTslGsdAsdCslAsdCslAsdGslAslA
(SEQ ID NO: 638)
1020 ATCAGCATGGACTG
(SEQ ID NO: 639)		 lAsdTslCsdAslGslCsdAsdTslGsdGslAsdCslTslG
(SEQ ID NO: 640)
1061 GCTTGGTGTTAACC
(SEQ ID NO: 641)		 lGsdCslTsdTslGslGsdTsdGslTsdTslAsdAslCslC
(SEQ ID NO: 642)
1188 TCCATGGCAGGGTT
(SEQ ID NO: 643)		 lTsdCslCsdAslTslGsdGsdCslAsdGslGsdGslTslT
(SEQ ID NO: 644)
1305 AGATAGCTGTCAAT
(SEQ ID NO: 645)		 lAsdGslAsdTslAslGsdCsdTslGsdTslCsdAslAslT
(SEQ ID NO: 646)
1443 CAGAAGTGGTAGTC
(SEQ ID NO: 647)		 lCsdAslGsdAslAslGsdTsdGslGsdTslAsdGslTslC
(SEQ ID NO: 648)
1447 GCTGCAGAAGTGGT
(SEQ ID NO: 649)		 lGsdCslTsdGslCslAsdGsdAslAsdGslTsdGslGslT
(SEQ ID NO: 650)
1518 ATGTCCATGGCATG
(SEQ ID NO: 651)		 lAsdTslGsdTslCslCsdAsdTslGsdGslCsdAslTslG
(SEQ ID NO: 652)
1560 ATCTTATAGCAGGC
(SEQ ID NO: 653)		 lAsdTslCsdTslTslAsdTsdAslGsdCslAsdGslGslC
(SEQ ID NO: 654)
1647 GCACTCTCAGTGCC
(SEQ ID NO: 655)		 lGsdCslAsdCslTslCsdTsdCslAsdGslTsdGslCslC
(SEQ ID NO: 656)
1662 TAGGCAGCCTTGTC
(SEQ ID NO: 657)		 lTsdAslGsdGslCslAsdGsdCslCsdTslTsdGslTslC
(SEQ ID NO: 658)
1694 TGAGGAGGTCCCCA
(SEQ ID NO: 659)		 lTsdGslAsdGslGslAsdGsdGslTsdCslCsdCslCslA
(SEQ ID NO: 660)
1755 ACACTCTGGCCCTT
(SEQ ID NO: 661)		 lAsdCslAsdCslTslCsdTsdGslGsdCslCsdCslTslT
(SEQ ID NO: 662)
1764 ACCTGCTCCACACT
(SEQ ID NO: 663)		 lAsdCslCsdTslGslCsdTsdCslCsdAslCsdAslCslT
(SEQ ID NO: 664)
1828 AGACACCAGCCACC
(SEQ ID NO: 665)		 lAsdGslAsdCslAslCsdCsdAslGsdCslCsdAslCslC
(SEQ ID NO: 666)
1912 CTCAAAGATCTCAA
(SEQ ID NO: 667)		 lCsdTslCsdAslAslAsdGsdAslTsdCslTsdCslAslA
(SEQ ID NO: 668)
2037 ATGAAGACCCAGTC
(SEQ ID NO: 669)		 lAsdTslGsdAslAslGsdAsdCslCsdCslAsdGslTslC
(SEQ ID NO: 670)
2218 CTTCTTGTCAGGCC
(SEQ ID NO: 671)		 lCsdTslTsdCslTslTsdGsdTslCsdAslGsdGslCslC
(SEQ ID NO: 672)
2253 TAGTGGACCACCTC
(SEQ ID NO: 673)		 lTsdAslGsdTslGslGsdAsdCslCsdAslCsdCslTslC
(SEQ ID NO: 674)
2481 AGGTTCTCCTTGTG
(SEQ ID NO: 675)		 lAsdGslGsdTslTslCsdTsdCslCsdTslTsdGslTslG
(SEQ ID NO: 676)
2518 GGGCTGTGTGGCCC
(SEQ ID NO: 677)		 lGsdGslGsdCslTslGsdTsdGslTsdGslGsdCslCslC
(SEQ ID NO: 678)
2738 CCTTCCTGCTGTCC
(SEQ ID NO: 679)		 lCsdCslTsdTslCslCsdTsdGslCsdTslGsdTslCslC
(SEQ ID NO: 680)
2961 TGGATGGTGAACAG
(SEQ ID NO: 681)		 lTsdGslGsdAslTslGsdGsdTslGsdAslAsdCslAslG
(SEQ ID NO: 682)
3186 TGCAGGGCCAGGTC
(SEQ ID NO: 683)		 lTsdGslCsdAslGslGsdGsdCslCsdAslGsdGslTslC
(SEQ ID NO: 684)
3255 ACCTTGGACTTGAT
(SEQ ID NO: 685)		 lAsdCslCsdTslTslGsdGsdAslCsdTslTsdGslAslT
(SEQ ID NO: 686)
3625 GCATTCCAGGTCCT
(SEQ ID NO: 687)		 lGsdCslAsdTslTslCsdCsdAslGsdGslTsdCslCslT
(SEQ ID NO: 688)
3794 GCAGGCTCAGCTGG
(SEQ ID NO: 689)		 lGsdCslAsdGslGslCsdTsdCslAsdGslCsdTslGslG
(SEQ ID NO: 690)
4253 CTGCACTGGCCTTG
(SEQ ID NO: 691)		 lCsdTslGsdCslAslCsdTsdGslGsdCslCsdTslTslG
(SEQ ID NO: 692)
4259 GCTTCTCTGCACTG
(SEQ ID NO: 693)		 lGsdCslTsdTslCslTsdCsdTslGsdCslAsdCslTslG
(SEQ ID NO: 694)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 695)		 lTsdTslGsdAslTslCsdTsdTslGsdGslCsdCslTslC
(SEQ ID NO: 696)
4318 CTGCAGCTCCTCCA
(SEQ ID NO: 697)		 lCsdTslGsdCslAslGsdCsdTslCsdCslTsdCslCslA
(SEQ ID NO: 698)
4416 TGACTGATCAGACA
(SEQ ID NO: 699)		 lTsdGslAsdCslTslGsdAsdTslCsdAslGsdAslCslA
(SEQ ID NO: 700)
4656 ATGGCATCTGCTTC
(SEQ ID NO: 701)		 lAsdTslGsdGslCslAsdTsdCslTsdGslCsdTslTslC
(SEQ ID NO: 702)
4717 TGCCTCCTGCAGCC
(SEQ ID NO: 703)		 lTsdGslCsdCslTslCsdCsdTslGsdCslAsdGslCslC
(SEQ ID NO: 704)
4773 AGCTTGGCCTTCTC
(SEQ ID NO: 705)		 lAsdGslCsdTslTslGsdGsdCslCsdTslTsdCslTslC
(SEQ ID NO: 706)
4802 TTACATCCTCTGAC
(SEQ ID NO: 707)		 lTsdTslAsdCslAslTsdCsdCslTsdCslTsdGslAslC
(SEQ ID NO: 708)
4837 AGCAGCTGCTGAGG
(SEQ ID NO: 709)		 lAsdGslCsdAslGslCsdTsdGslCsdTslGsdAslGslG
(SEQ ID NO: 710)
4904 TCTCCTCCTCCTGC
(SEQ ID NO: 711)		 lTsdCslTsdCslCslTsdCsdCslTsdCslCsdTslGslC
(SEQ ID NO: 712)
6033 CCCTTAAGGGCCTC
(SEQ ID NO: 713)		 lCsdCslCsdTslTslAsdAsdGslGsdGslCsdCslTslC
(SEQ ID NO: 714)
6099 AGGTTCTTCCTGTC
(SEQ ID NO: 715)		 lAsdGslGsdTslTslCsdTsdTslCsdCslTsdGslTslC
(SEQ ID NO: 716)
6142 GACCTTGCTCTGCA
(SEQ ID NO: 717)		 lGsdAslCsdCslTslTsdGsdCslTsdCslTsdGslCslA
(SEQ ID NO: 718)
6149 AGCTCTTGACCTTG
(SEQ ID NO: 719)		 lAsdGslCsdTslCslTsdTsdGslAsdCslCsdTslTslG
(SEQ ID NO: 720)
6220 GTGCTGGGCCTTGC
(SEQ ID NO: 721)		 lGsdTslGsdCslTslGsdGsdGslCsdCslTsdTslGslC
(SEQ ID NO: 722)
6273 TTGTTGGCCTGGGT
(SEQ ID NO: 723)		 lTsdTslGsdTslTslGsdGsdCslCsdTslGsdGslGslT
(SEQ ID NO: 724)
6277 CAGCTTGTTGGCCT
(SEQ ID NO: 725)		 lCsdAslGsdCslTslTsdGsdTslTsdGslGsdCslCslT
(SEQ ID NO: 726)
SEQ ID NO: 6의 표적 서열의 시작 뉴클레오티드 서열(5'-3') 변형을 가진 서열(5'-3')
4302 +TT+GA+T+CTT+GG+CC+T+C
(SEQ ID NO: 727)		 lTsdTslGsdAslTslCsdTsdTslGsdGslCsdCslTslC
(SEQ ID NO: 728)
4302 +TT+GA+TC+T+T+GGC+CT+C
(SEQ ID NO: 729)		 lTsdTslGsdAslTsdCslTslTslGsdGsdCslCsdTslC
(SEQ ID NO: 730)
4302 lTslTslGsdAsdTsmdCsdTsdTsdGsdGsmdCslCslTslC
(SEQ ID NO: 731)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 732)		 eTseTseGsdAsdTsmdCsdTsdTsdGsdGsmdCseCseTseC
(SEQ ID NO: 733)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 734)		 lTslTsmGsdAsdTsmdCsdTsdTsdGsdGsmdCsmCslTslC
(SEQ ID NO: 735)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 736)		 eTseTslGsdAsdTsmdCsdTsdTsdGsdGsmdCseCseTseC
(SEQ ID NO: 737)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 738)		 eTslTslGsdAsdTsmdCsdTsdTsdGsdGsmdCslCslTslC
(SEQ ID NO: 739)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 740)		 lTseTslGsdAsdTsmdCsdTsdTsdGsdGsmdCslCslTslC
(SEQ ID NO: 741)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 742)		 lTslTseGsdAsdTsmdCsdTsdTsdGsdGsmdCslCslTslC
(SEQ ID NO: 743)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 744)		 lTslTslGsdAsdTsmdCsdTsdTsdGsdGsmdCseCslTslC
(SEQ ID NO: 745)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 746)		 lTslTslGsdAsdTsmdCsdTsdTsdGsdGsmdCslCseTslC
(SEQ ID NO: 747)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 748)		 lTslTslGsdAsdTsmdCsdTsdTsdGsdGsmdCslCslTseC
(SEQ ID NO: 749)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 750)		 lTslTslGdAdTmdCdTdTdGdGmdClCslTslC
(SEQ ID NO: 751)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 752)		 lTslTslGsdAdTmdCdTdTdGdGmdCslCslTslC
(SEQ ID NO: 753)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 754)		 lTslTslGdAsdTmdCsdTdTsdGdGsmdClCslTslC
(SEQ ID NO: 755)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 756)		 lTslTlGsdAdTsmdCdTsdTdGsdGmdCslClTslC
(SEQ ID NO: 757)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 758)		 lTslTslGdAsdTsmdCsdTdTsdGsdGsmdClCslTslC
(SEQ ID NO: 759)
4318 CTGCAGCTCCTCCA
(SEQ ID NO: 760)		 lCslTsmGsmdCsdAsdGsmdCsdTsmdCsmdCsdTsmCslCslA
(SEQ ID NO: 761)
4318 CTGCAGCTCCTCCA
(SEQ ID NO: 762)		 lCslTslGmdCsdAdGsmdCdTsmdCmdCsdTlCslCslA
(SEQ ID NO: 763)
4318 CTGCAGCTCCTCCA
(SEQ ID NO: 764)		 lCslTslGmdCsdAsdGsmdCdTsmdCsmdCsdTlCslCslA
(SEQ ID NO: 765)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 766)		 lTsmUslGsdAsdTsmdCsdTsdTsdGsdGsmdCslCsmuslC
(SEQ ID NO: 767)
4302 TTGATCTTGGCCTC
(SEQ ID NO: 768)		 lTslTsfGsdAsdTsmdCsdTsdTsdGsdGsmdCsfCslTslC
(SEQ ID NO: 769)
4661 lTslCsmUsdGsdGsdAsdTsdGsdGsmdCsdAsmUslCslT
(SEQ ID NO: 770)
892 lGslAsmCsdTsdGsdGsdGsdAsdGsmdCsmdCsmAslTslT
(SEQ ID NO: 771)
2360 lCslCsmAsdGsdGsdAsdGsmdCsmdCsdTsdAsmUslTslC
(SEQ ID NO: 772)
1417 lAslGsmAsmdCsdAsdGsdAsdAsdGsmdCsdAsmGslCslA
(SEQ ID NO: 773)
516 lAslGsmUsdTsmdCsdAsmdCsdTsmdCsdAsmdCsmAslTslC
(SEQ ID NO: 774)
1582 lAslAsmAsdGsdTsdGsmdCsdAsdGsdGsdAsmGslGslG
(SEQ ID NO: 775)
1217 lTslCsmCsdTsmdCsdAsdGsdGsdGsdTsmdCsmUslTslG
(SEQ ID NO: 776)
515 lGslTsmUsmdCsdAsmdCsdTsmdCsdAsmdCsdAsmUslCslC
(SEQ ID NO: 777)
514 lTslTsmCsdAsmdCsdTsmdCsdAsmdCsdAsdTsmCslCslA
(SEQ ID NO: 778)
1424 lGslGsmUsdTsmdCsdAsdTsdAsdGsdAsmdCsmAslGslA
(SEQ ID NO: 779)
1219 lAslTsmUsmdCsmdCsdTsmdCsdAsdGsdGsdGsmUslCslT
(SEQ ID NO: 780)
513 lTslCsmAsmdCsdTsmdCsdAsmdCsdAsdTsmdCsmCslAslT
(SEQ ID NO: 781)
1226 lAslGsmUsdTsdAsdTsmdCsdAsdTsdTsmdCsmCslTslC
(SEQ ID NO: 782)
1225 lGslTsmUsdAsdTsmdCsdAsdTsdTsmdCsmdCsmUslCslA
(SEQ ID NO: 783)
1645 lAslCsmUsmdCsdTsmdCsdAsdGsdTsdGsmdCsmCslAslT
(SEQ ID NO: 784)
4302 avTsavTsavGsdAsdTsmdCsdTsdTsdGsdGsmdCsavCsavTsavC
(SEQ ID NO: 785)
3257 avGsavCsavAsdCsdCsdTsdTsdGsdGsdAsdCsavTsavTsavG
(SEQ ID NO: 786)
2483 avTsavGsavAsdGsdGsdTsdTsdCsdTsdCsdCsavTsavTsavG
(SEQ ID NO: 787)
l = 잠금 뉴클레오티드; d = 데옥시뉴클레오티드; mdC = 5-메틸 시토신; f = 2'-플루오로 뉴클레오티드; av = 아미노-CBBN 뉴클레오티드; s = 포스포로티오에이트 결합; e = 에틸렌-가교 뉴클레오티드
변형을 가진 서열(5'-3')
lGslTsdGsdAsdAsdTsdGsdCsdGsdGsdAsdTslGslAslA
(SEQ ID NO: 789)
lGslAslAsdGsdTsdGsdGsdTsdAsdGsdTsdCsdAslTslA
(SEQ ID NO: 790)
lGsdTslGsdAsdAslTslGsdCsdGslGsdAslTsdGslAslA
(SEQ ID NO: 791)
lGsdAslAsdGsdTslGslGsdTsdAslGsdTslCsdAslTslA
(SEQ ID NO: 792)
한 실시태양에서, 본 발명은 MYH7B의 억제제를 포함하는 조성물을 대상에게 투여하는 단계를 포함하여 β-MHC의 발현이 대상의 심장 세포에서 상향 조절되는 심장 질환을 치료 또는 예방하는 방법을 제공한다. 또 다른 실시태양에서, 본 발명은 대상에게 MYH7B의 억제제를 포함하는 조성물을 투여하는 단계를 포함하여 대상의 심장 세포에서 β-MHC/α-MHC의 비율이 변경되는 심장 질환을 치료 또는 예방하는 방법을 제공한다. 예를 들어, 본 발명은 MYH7B의 억제제를 사용하여 대상의 심장 세포에서 β-MHC의 발현 또는 활성을 억제 및/또는 β-MHC/α-MHC의 비율을 변경함으로써 병적 심근비대증, 심근경색증, 심부전증 또는 비대성 심근병증으로 이루어진 그룹으로부터 선택된 심장 질환을 치료 또는 예방하기 위한 조성물 및 방법을 제공한다. 대상에 대한 MYH7B의 억제제의 투여는 투여 후 대상의 심장 세포에서 MYH7B의 발현 또는 활성을 하향 조절한다. 한 실시태양에서, MYH7B의 억제제의 투여는 대상의 심장 세포에서 myomiRs, 특히 miR-499의 발현 또는 활성을 현저하게 변화시키지 않는다. 따라서, 일부 실시태양에서, 심근 세포에서 miR-499, miR-208a 및/또는 miR-208b의 발현은 MYH7B 억제제의 투여 후 통계적으로 상이하지 않다.
다양한 실시태양에서, 본 발명에 의해 제공된 방법은 본 발명에 개시된 하나 이상의 핵산 억제제를 투여하는 단계를 포함한다. 예를 들어, 한 실시태양에서, 본 발명에 의해 제공된 방법은 표 1-5로부터 선택되는 안티센스 올리고뉴클레오티드 억제제를 투여하는 단계를 포함한다. 또 다른 실시태양에서, 본 발명에 따른 방법은 SEQ ID NO: 146의 서열을 포함하는 안티센스 올리고뉴클레오티드 억제제를 투여하는 단계를 포함한다. 또 다른 실시태양에서, 본 발명에 따른 방법은 SEQ ID NO: 148의 서열을 포함하는 안티센스 올리고뉴클레오티드 억제제를 투여하는 단계를 포함한다.
한 특정 실시태양에서, 본 발명은 MYH7B의 억제제를 포함하는 조성물을 대상에게 투여하는 단계를 포함하여 필요한 대상에서 비대성 심근병증을 치료 또는 예방하는 방법을 제공하며, MYH7B의 발현 또는 활성이 억제제의 투여 후 대상의 심장 세포에서 감소된다. 한 실시태양에서, 대상에 대한 MYH7B의 억제제의 투여는 투여 후 대상의 심장 세포에서 β-MHC의 발현 또는 활성을 감소시킨다.
한 실시태양에서, 본 발명은 병적 심근비대증 또는 비대성 심근병증의 발병 위험이 있는 대상에서 병적 심근비대증 또는 비대성 심근병증을 치료 또는 예방하는 방법을 제공한다. 병적 심근비대증 또는 비대성 심근병증의 발병 위험이 있는 환자는, 예를 들어, 장기의 비 통제된 고혈압, 교정되지 않은 판막 질환, 만성 협심증, 최근의 심근 경색증, 심장 질환에 대한 선천적 소인 또는 병적 비대증을 포함하는 하나 이상의 위험 인자를 나타낼 수 있다. 일부 실시태양에서, 위험이 있는 대상은 병적 심근비대증 또는 비대성 심근병증에 유전적 소인을 갖는 것으로 진단될 수 있다. 예를 들어, 특정 실시태양에서, 위험이 있는 대상은 근절 유전자에 하나 이상의 돌연변이, 예를 들어 β-MHC(MYH7) 유전자의 돌연변이를 보유할 수 있다. 한 실시태양에서, 위험이 있는 대상은 Arg663His, Lys207Asn, Gly256Glu, Arg403Gln, Arg453Cys, Gly584Arg, Arg719Trp, Arg723Gly, Ile736Thr, Gly741Arg, Asp778Gly, Asp778Val, Asp906Gly 및 Leu908Val로부터 선택된 β-MHC(MYH7) 유전자에 하나 이상의 돌연변이를 가진다. 특정 실시태양에서, 위험이 있는 대상은 β-MHC(MYH7) 유전자에 Arg403Gln, Arg453Cys 또는 Arg719Trp 돌연변이를 가진다. 비대성 심근병증과 관련된 근절 유전자에 다른 돌연변이는 당해 기술분야의 당업자에게 공지되어 있으며(예를 들어, 전문이 참조로 본 발명에 포함된, Moore et al, Circulation Research, Vol. 111:375-385, 2012 참조), 병적 심근비대증 또는 비대성 심근병증의 발병 위험이 있는 대상을 확인하는데 사용될 수 있다. 다른 특정 실시태양에서, 위험이 있는 대상은 병적 심근비대증 또는 비대성 심근병증의 가족력을 가질 수 있다.
다른 실시태양에서, 본 발명은 대상에게 MYH7B의 억제제를 투여하는 단계를 포함하여 대상의 심장 세포에서 β-MHC의 발현 또는 활성을 억제하기 위한 조성물 및 방법을 제공한다. 또 다른 실시태양에서, 본 발명은 대상에게 MYH7B의 억제제를 투여하는 단계를 포함하는, 대상의 심장 세포에서 β-MHC/α-MHC의 비율을 조절하기 위한 조성물 및 방법을 제공한다. 대상에 대한 MYH7B의 억제제의 투여는 MYH7B의 억제제에 의한 치료 전에 MYH7B 및 β-MHC의 발현 또는 활성과 비교하여 대상의 심장 세포에서 MYH7B의 발현 또는 활성 및/또는 β-MHC의 발현 또는 활성을 감소시킨다. 한 실시태양에서, 대상에게 대한 MYH7B의 억제제의 투여는 건강한 대상에서 발견된 정상 수준으로 대상의 심장 세포에서 β-MHC/α-MHC 비율을 완전 또는 부분적으로 회복시킨다.
본 발명의 한 양태에 따라, 대상에 대한 MYH7B의 억제제의 투여는 심장 질환의 하나 이상의 증상의 개선을 초래한다. 예를 들어, 한 실시태양에서, MYH7B 억제제의 투여는 대상에서 병적 심근비대증, 심근경색증 또는 심부전증의 하나 이상의 증상의 개선 또는 병적 심근비대증에서 심부전증으로의 전환의 지연을 초래한다. 다른 실시태양에서, MYH7B 억제제의 투여는 대상에서 병적 심근비대증, 심근경색증 또는 심부전증의 개시에 지연을 초래한다. 하나 이상의 개선된 증상은, 예를 들어, 증가된 운동 능력, 증가된 심장 배출 부피, 감소된 좌심실 이완 말기 압력, 감소된 폐 모세혈관 쐐기 압력, 증가된 심박출량, 증가된 심지수, 감소된 폐동맥 압력, 감소된 좌심실 수축 및 이완 말기 치수, 감소된 심장 섬유증, 심근의 감소된 콜라겐 침착, 감소된 좌심실 및 우심실 벽 스트레스, 감소된 벽 긴장, 삶의 질 향상, 및 감소된 질병 관련 이환율 또는 사망률이다.
일부 실시태양에서, MYH7B의 억제제는 앱타머이다. 본 발명에 사용된 용어 "앱타머"는 고전적인 왓슨-크릭 염기쌍 형성 이외의 상호 작용을 통해 특정 표적 분자에 대한 특이적 결합 친화력을 갖는 핵산 분자를 의미한다. 이 앱타머는 표적 분자에 결합함으로써 표적 분자의 활성 또는 기능을 억제할 수 있다. 일부 실시태양에서, 본 발명의 앱타머는 MYH7B 단백질의 하나 이상의 에피토프에 결합한다. 특정 실시태양에서, 앱타머는 인간 MYH7B 단백질에 결합한다. 항-MHH7B 앱타머는 리보뉴클레오티드, 데옥시리보뉴클레오티드, 변형 뉴클레오티드 또는 이의 혼합물로 구성될 수 있다. 예를 들어, 앱타머는 하나 이상의 2'-O-알킬(예를 들어, 2'-O-메틸) 또는 2'-할로 (예를 들어, 2'-플루오로) 변형을 포함할 수 있다. 일부 실시태양에서, 상기 앱타머는 앱타머의 순환 반감기를 향상시키기 위해 중합체, 예를 들어 PEG 폴리머에 접합될 수 있다.
MYH7B에 대한 앱타머는 미국특허 제 5,270,163호에 기술된 바와 같이, 지수 적 농축에 의한 리간드의 체계적인 진화(SELEX)를 사용하여 확인될 수 있다(Tuerk & Gold, Science 249:505-510, 1990; Ellington & Szostak, Nature 346:818-822, 1990). 핵산의 라이브러리는 표적 MYH7B와 접촉될 수 있으며, 표적에 특이적으로 결합된 핵산은 표적에 특이적으로 결합하지 않는 라이브러리 내의 핵산의 나머지로부터 분할된다. 분할된 핵산은 증폭되어 리간드가 풍부한 풀을 생성한다. 다수의 결합, 분할 및 증폭(즉, 선택)의 여러 사이클은 원하는 활성을 갖는 하나 이상의 앱타머의 동정을 초래한다. 미국 특허공보 제 20090264508호에 기술된 레이저 SELEX 또는 deSELEX와 같은 변형된 방법이 또한 사용될 수 있다.
특정 실시태양에서, MYH7B의 발현 또는 활성을 억제하는데 유용한 앱타머의 길이는 약 10 내지 약 30개 뉴클레오티드, 약 15 내지 약 35개 뉴클레오티드, 약 20 내지 약 35개 뉴클레오티드, 약 20 내지 약 40개 뉴클레오티드, 또는 약 25 내지 약 50개 뉴클레오티드이다.
일부 실시태양에서, MYH7B의 억제제는 리보자임이다. 용어 "리보자임"은 촉매 활성을 갖는 RNA 분자를 의미한다. 다양한 활성을 갖는 리보자임이 공지되어 있다. 선택적으로, 표적 특이적 RNA 절단 활성을 갖는 리보자임이 설계될 수 있다. 특정 실시태양에서, MYH7B의 억제제로서 사용될 수 있는 리보자임은 그룹 I 및 그룹 II 인트론 유형 리보자임, 해머헤드 리보자임 및 헤어핀 리보자임과 같은 공지된 또는 인공적으로 생성된 RNase P 리보자임을 포함한다. 일부 실시태양에서, MYH7B의 억제제로서 사용될 수 있는 리보자임은 약 200 내지 약 500개 뉴클레오티드 또는 약 300 내지 약 450개 뉴클레오티드의 길이를 가진다. 다른 실시태양에서, MYH7B의 리보자임 억제제는 약 30 내지 약 100개 뉴클레오티드, 약 40 내지 약 80개 뉴클레오티드, 또는 약 40 내지 약 60개 뉴클레오티드의 길이를 가질 수 있다.
한 실시태양에서, MYH7B의 억제제는 소형 간섭 RNA이다. 본 발명에 사용된 용어 "소형 간섭" 또는 "짧은 간섭 RNA" 또는 "siRNA"는 MYH7B 유전자를 표적으로 하고 MYH7B 유전자의 발현을 억제할 수 있는 뉴클레오티드의 RNA 이중 가닥을 의미한다. 특정 실시태양에서, MYH7B의 억제제로서 사용될 수 있는 siRNA는 약 10 내지 약 30개 뉴클레오티드, 특히 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 또는 30개 염기쌍을 형성하고 1개 또는 2개의 뉴클레오티드의 5' 및/또는 3' 오버행(overhang)을 소유하는 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 또는 30개 뉴클레오티드의 2개의 상보적인 단일 가닥 RAN를 포함한다. siRNA 이중 가닥은 MYH7B 유전자의 서열과 실질적으로 동일한 서열을 갖는 제 1 가닥 및 제 1 가닥에 부분적으로, 실질적으로 또는 완전히 상보적인 서열을 갖는 제 2 가닥을 포함한다. 특정 실시태양에서, MYH7B siRNA의 제 1 가닥은 MYH7B 유전자의 서열과 적어도 70%, 75%, 80%, 85%, 90%, 95%, 96%, 98%, 99% 또는 100% 동일한 서열을 포함하며 제 2 가닥은 제 1 가닥에 실질적으로 또는 완전히 상보적인 서열을 포함한다. 일부 실시태양에서, MYH7B 유전자를 표적으로 하는 siRNA의 제 1 RNA 가닥은 인간 MYH7B 유전자(SEQ ID NO: 6)의 암호화 영역과 적어도 70%, 75%, 80%, 85%, 90%, 95% 또는 100% 동일하다. 특정 실시태양에서, MYH7B 유전자를 표적으로 하는 siRNA의 제 1 RNA 가닥은 5'-GAGGCCAAGATCAA-3'의 서열(SEQ ID NO: 4)과 적어도 70%, 75%, 80%, 85%, 90%, 95% 또는 100% 동일하다. 다른 실시태양에서, MYH7B 유전자를 표적으로 하는 siRNA의 제 1 RNA 가닥은 5'-TGGAGGAGCTGCAG-3'의 서열(SEQ ID NO: 5)과 적어도 70%, 75%, 80%, 85%, 90%, 95% 또는 100% 동일하다. MYH7B의 siRNA 억제제는 심장 세포에 투여되거나 하나 이상의 벡터로부터 심장 세포에서 발현될 수 있다.
다른 실시태양에서, MYH7B의 억제제는 소형 헤어핀 RNA(shRNA)이다. 본 발명에 사용된 용어 "shRNA"는 이중 가닥의 일부가 헤어핀 구조 (shRNA)의 일부인 RNA 이중 가닥을 의미한다. 이중 부분 이외에, 헤어핀 구조는 이중 구조를 형성하는 두 개의 제 1 및 제 2 가닥 사이에 위치된 루프 부분을 함유할 수 있다. 루프는 길이가 다를 수 있다. 일부 실시태양에서, 루프는 5, 6, 7, 8, 9, 10, 11, 12 또는 13개 뉴클레오티드 길이이다. 헤어핀 구조는 또한 3'또는 5' 오버행을 포함할 수 있다. 일부 양태에서, 오버행은 0, 1, 2, 3, 4 또는 5개 뉴클레오티드 길이의 3'또는 5' 오버행이다. MYH7B를 표적으로 하는 shRNA의 이중 가닥 부분 또는 이중 가닥 영역은 약 10 내지 약 30개 뉴클레오티드 길이이고 적어도 MYH7B 유전자의 서열과 적어도 70%, 75%, 80%, 85%, 90%, 95%, 96%, 98%, 99% 또는 100% 동일한 제 1 RNA 가닥 및 제 1 가닥에 실질적으로 또는 완전히 상보적인 제 2 가닥을 포함한다. 특정 실시태양에서, MYH7B 유전자를 표적으로 하는 이중 가닥 부분의 제 1 RNA 가닥은 인간 MYH7B 유전자(SEQ ID NO: 6)의 암호화 영역과 적어도 70%, 75%, 80%, 85%, 90%, 95% 또는 100% 동일하다. 일부 실시태양에서, MYH7B 유전자를 표적으로 하는 이중 가닥 부분의 제 1 RNA 가닥은 5'-GAGGCCAAGATCAA-3'의 서열(SEQ ID NO: 4)과 적어도 70%, 75%, 80%, 85%, 90%, 95% 또는 100% 동일하다. 다른 실시태양에서, MYH7B 유전자를 표적으로 하는 이중 가닥 부분의 제 1 RNA 가닥은 5'-TGGAGGAGCTGCAG-3'의 서열(SEQ ID NO: 5)과 적어도 70%, 75%, 80%, 85%, 90%, 95% 또는 100% 동일하다. MYH7B의 siRNA 억제제는 심장 세포에 투여되거나 한 벡터로부터 심장 세포에서 발현될 수 있다.
안티센스 올리고뉴클레오티드와 유사하게, 본 발명에 기술된 다른 억제 뉴클레오티드 분자(앱타머, 리보자임, siRNA, shRNA)는 상기 하나 이상의 화학적으로 변형된 뉴클레오티드를 함유할 수 있다. 예를 들어, MYH7B를 표적으로 하는 억제 뉴클레오티드 분자는 2'-O-알킬 (예를 들어, 2'-O-메틸, 2'-O-메톡시에틸), 2'-할로(예를 들어, 2'-플루오로, 2'-클로로, 2'-브로모) 및 4' 티오 변형과 같은 바이사이클릭 당 뉴클레오시드(BSN) 변형, 잠금 핵산(LNA) 변형, 당 변형, 하나 이상의 포스포로티오에이트, 모르폴리노 또는 포스포노카복실레이트 결합과 같은 주쇄 변형, 5- 메틸시티딘 또는 2'-4'-가교 바이사이클릭 뉴클레오시드 변형과 같은 염기 변형을 포함한다.
또 다른 실시태양에서, MYH7B의 억제제는 MYH7B 단백질의 하나 이상의 에피토프에 특이적으로 결합하는 항체 또는 이의 결합 단편이다. 예를 들어, 특정 실시 태양에서, MYH7B의 억제제는 MYH7B 단백질의 하나 이상의 에피토프에 특이적으로 결합하는 단클론 또는 다클론 항체이다. 단클론 항체는 키메릭화 또는 인간화될 수 있다. 다른 실시태양에서, MYH7B의 억제제는 MYH7B-특이적 항체로부터 유래된 단편이며, 이 단편은 MYH7B 단백질의 하나 이상의 에피토프에 특이적으로 결합한다. 이러한 결합 단편은 Fab 단편, scFv 단편, 또는 다이아바디(diabody), 트라이바디 (triabody), 미니바디(minibody) 또는 단일 도메인 항체와 같은 조작된 항체 단편을 포함할 수 있다. 항-MYH7B 항체는 IgM, IgG, IgD, IgE 및 IgA 또는 IgG 서브 클래스(예를 들어, IgG1, IgG2, IgG2a, IgG2b, IgG3 또는 IgGM)를 포함하는 이들의 서브 클래스와 같은 모든 면역글로불린 클래스를 포함한다. 바람직하게는, 항-MYH7B 항체 또는 이의 결합 단편은 약 1 x 10-7 M 내지 약 1 x 10-12 M, 약 1 x 10-8 M 내지 약 1 x 10-11 M, 또는 약 1 x 10-9 M 내지 약 5 x 10-10 M 범위의 MYH7B에 대한 결합 친화력을 가진다.
본 발명에 사용된 용어 "대상" 또는 "환자"는 인간 및 다른 영장류(예를 들어, 침팬지 및 다른 유인원 및 원숭이 종), 농장 동물(예를 들어, 소, 양, 돼지, 염소 및 말), 가정용 포유류 (예를 들어, 개 및 고양이), 실험용 동물(예를 들어, 생쥐, 쥐 및 기니피그 등의 설치류) 및 조류(예를 들어, 닭, 칠면조 및 다른 가금류, 오리, 오리, 거위 등과 같은 가정용, 야생용 및 경기용 조류)를 포함하나 이에 제한되지 않는 임의의 척추동물을 의미한다. 일부 실시태양에서, 대상은 포유동물이다. 다른 실시태양에서, 대상은 인간이고 억제 분자는 인간 MYH7B 유전자, mRNA, 전 mRNA 또는 단백질을 표적으로 한다.
본 발명에 기술된 MYH7B의 임의의 핵산 억제제는 세포에 MYH7B 억제제를 암호화하는 발현 벡터를 전달함으로써 표적 세포(예를 들어, 심장 세포 및 골격근 세포)에 전달될 수 있다. "벡터"는 관심 핵산을 세포의 내부로 전달하기 위해 사용될 수 있는 물질의 조성물이다. 선형 폴리뉴클레오티드, 이온성 또는 친양쪽성 화합물과 연관된 폴리뉴클레오티드, 플라스미드, 및 바이러스를 포함하지만 여기에 제한되지 않는 여러 벡터가 당업계에 알려져 있다. 따라서 용어 "벡터"는 자율적으로 복제하는 플라스미드 또는 바이러스를 포함한다. 바이러스성 벡터의 예는 아데노바이러스 벡터, 아데노-연관 바이러스 벡터, 레트로바이러스 벡터 등을 포함하나 여기에 제한되지 않는다. 발현 구조체(expression construct)는 살아있는 세포(living cell)에서 복제되거나 또는 합성적으로 만들어질 수 있다. 본 출원의 목적을 위하여, 용어 "발현 구조체", "발현 벡터", 및 "벡터"라는 용어는 일반적이고, 설명적인 의미에서 본 발명의 출원을 설명하기 위해 상호 교환적으로 사용되며 본 발명을 제한하려는 것은 아니다.
한 실시태양에서, MYH7B의 억제제를 발현하기 위한 발현 벡터는 5'-TTGATCTTGGCCTC-3'의 서열을 포함하는 안티센스 올리고뉴클레오티드를 암호화하는 폴리뉴클레오티드에 작동 가능하게 연결된 프로모터를 포함한다. 다른 실시태양에서, MYH7B의 억제제를 발현하기 위한 발현 벡터는 5'-CTGCAGCTCCTCCA-3'의 서열을 포함하는 안티센스 올리고뉴클레오티드를 암호화하는 폴리뉴클레오티드에 작동 가능하게 연결된 프로모터를 포함한다. 본 발명에서 사용된 "작동가능하게 연결된(operably linked)" 또는 "전사 조절 하에서(under transcriptional control)"라는 문구는 프로모터가 RNA 중합효소 및 폴리뉴클레오티드의 발현에 의해 전사의 개시를 제어하기 위해 폴리뉴클레오티드에 대한 관계에서 정확한 위치와 방향에 있다는 것을 의미한다.
본 발명에 사용된 대로, "프로모터"는 세포의 합성 기관(synthetic machinery) 또는 유전자의 특정 전사를 시작하기에 필요한 유도된 합성 기관(induced synthetic machinery)에 의해 인식된 DNA 서열을 의미한다. 적합한 프로모터는 RNA 중합효소I(polI), RNA 중합효소II(polII), RNA 중합효소III(polIII), 및 바이러스성 프로모터(viral promoter)(예를 들어, 인간 세포거대바이러스 즉각 조기 유전자 프로모터(human cytomegalovirus (CMV) immediate early gene promoter), SV40 초기 프로모터(SV40 early promoter), 및 라우스육종바이러스 긴말단 반복(the Rous sarcoma virus long terminal repeat)를 포함하나 이에 제한되는 것은 아니다. 한 실시태양에서, 프로모터는 조직 특이적 프로모터이다. 특히 관심 있는 것은 근육 특이적 프로모터들이며, 더욱 특히 심장 특이적 프로모터들이다. 이들은 미오신 경쇄-2 프로모터(the myosin light chain-2 promoter)(Franz et al. (1994) Cardioscience, Vol. 5(4):235-43; Kelly et al (1995) J. Cell Biol, Vol. 129(2):383-396), 알파 액틴 프로모터(the alpha actin promoter)(Moss et al (1996) Biol. Chem ., Vol. 271(49):31688-31694), 트로포닌 1 프로모터(the troponin 1 promoter)(Bhavsar et al. (1996) Genomics, Vol. 35(1): 11-23); Na+/Ca2+ 교환기 프로모터(the Na+/Ca2+ exchanger promoter)(Barnes et al (1997) J. Biol . Chem., Vol. 272(17):11510-11517), 디스트로핀 프로모터(the dystrophin promoter)(Kimura et al. (1997) Dev . Growth Differ., Vol. 39(3):257-265), 알파7 인테그린 프로모터(the alpha7 integrin promoter)(Ziober and Kramer (1996) J. Bio. Chem., Vol. 271(37):22915-22), 뇌 나트륨이뇨 펩타이드 프로모터(the brain natriuretic peptide promoter)(LaPointe et al (1996) Hypertension, Vol. 27(3 Pt 2):715-22) 및 알파 B-크리스탈린/소형열충격단백질 프로모터(the alpha B-crystallin/small heat shock protein promoter)(Gopal-Srivastava (1995) J. MoI . Cell. Biol, Vol. 15(12):7081-709O), 알파 미오신 중쇄 프로모터(alpha myosin heavy chain promoter)(Yamauchi-Takihara et al (1989) Proc . Natl . Acad . Sci USA, Vol. 86(10):3504-3508) 및 ANF 프로모터(ANF promoter)(LaPointe et al. (1988) J. Biol. Chem., Vol. 263(19):9075-9078)를 포함한다.
특정 실시태양에서, MYH7B 억제제를 암호화하는 폴리뉴클레오티드에 작동 가능하게 연결된 프로모터는 유도성 프로모터일 수 있다. 유도성 프로모터는 당업계에 공지되어 있으며 테트라사이클린 프로모터(tetracycline promoter), 메탈로티오네인 IIA 프로모터(metallothionein IIA promoter), 열충격 프로모터(heat shock promoter), 스테로이드/갑상선호르몬/레티노산 반응 요소(steroid/thyroid hormone/retinoic acid response elements), 아데노바이러스 후기 프로모터(the adenovirus late promoter), 및 유도성 생쥐 유방 종양 바이러스 LTR(the inducible mouse mammary tumor virus LTR)을 포함하나 이에 제한되지 않는다.
발현 구조체와 핵산을 세포에 전달하는 방법은 당업계에 공지되어 있고, 예를 들어, 인산칼슘 공동 침전, 전기천공법, 미세주사, DEAE-덱스트란, 리포펙션, 폴리아민 형질감염 시약을 사용하는 형질감염, 세포 초음파, 고속 미세추진체를 사용하는 유전자 충돌 및 수용체-매개 형질감염을 포함할 수 있다.
또한, 본 발명은 MYH7B의 억제제(예, 안티센스 올리고뉴클레오티드, 앱타머, 리보자임, siRNA, shRNA 또는 항체) 및 약학적으로 허용가능한 담체 또는 부형제를 포함하는 약학적 조성물을 포함한다. 예를 들어, 본 발명은 MYH7B의 안티센스 올리고뉴클레오티드 및 약학적으로 허용가능한 담체 또는 부형제를 포함하는 조성물을 제공한다.
한 실시태양에서, 약학적 조성물은 유효량의 MYH7B 억제제 및 약학적으로 허용가능한 담체를 포함한다. 예를 들어, 약학적 조성물은 MYH7B를 표적으로 하는 유효량의 안티센스 올리고뉴클레오티드 또는 본 발명에 기재된 MYH7B를 표적으로 하는 유효량의 변형 안티센스 올리고뉴클레오티드를 포함한다. 한 실시태양에서, 약학적 조성물은 5'-lTslTslGsdAsdTsdCsdTsdTsdGsdGsdCslCslTslC-3'(SEQ ID NO: 146)의 서열을 갖는 안티센스 올리고뉴클레오티드를 포함한다. 다른 실시태양에서, 약학적 조성물은 5'-lCslTslGsdCsdAsdGsdCsdTsdCsdCsdTslCslCslA-3'(SEQ ID NO: 148)의 서열을 갖는 안티센스 올리고뉴클레오티드를 포함한다. 일부 다른 실시태양에서, 약학적 조성물은 표 1-5에 열거된 서열로부터 선택된 서열을 갖는 안티센스 올리고뉴클레오티드 및 변형 안티센스 올리고뉴클레오티드를 포함한다.
"유효량"은 유익한 또는 원하는 임상 결과를 얻기에 충분한 양이다. 본 발명의 MYH7B 억제제의 유효량은 약 1 mg/kg 내지 약 100 mg/kg, 약 2.5 mg/kg 내지 약 50 mg/kg 또는 약 5 mg/kg 내지 약 25 mg/kg 일 수 있다. 유효량으로 생각될 양의 정확한 결정은 크기, 연령, 장애 유형(예를 들어, 비대성 심근병증, 심근경색증, 심부전증 또는 심장비대증) 및 억제제의 성질(예를 들어, 안티센스 올리고뉴클레오티드, siRNA, shRNA, 발현 구조체, 항체 등)을 포함하여 각 환자에게 개별적인 요인에 기반할 수 있다. 따라서, 투여량은 본 발명 및 당업계의 지식으로부터 당업자에 의해 용이하게 확인될 수 있다.
특정 실시태양에서, 본 발명은 MYH7B의 억제제 및 제 2 치료제를 투여하는 것을 포함하여, 병적 심근비대증, 심근경색증, 심부전증 또는 비대성 심근병증을 치료 또는 예방하는 방법을 제공한다. 일부 실시태양에서, 제 2 치료제는 miR-208a, miR-208b, miR-499, miR-15a, miR-15b, miR-16, miR-195 또는 이들의 조합 의 안티센스 올리고뉴클레오티드 억제제와 같은 심장 치료제이다. 이러한 miRNA의 예시적인 억제제는 WO 2012/083005 및 WO 2013/192486에 기재되어 있으며, 이들의 전문이 본 발명에 참고로 포함된다. 제 2 치료제가 포함되는 실시태양에서, 제 2 제제는 동시에 투여되지만 별도의 제형으로 또는 순차적으로 투여될 수 있다. 다른 실시태양에서, 제 2 치료제는 MYH7B 억제제의 투여 이전 또는 이후 상이한 시간에 투여될 수 있다. 사전 투여는, 예를 들어, 제 2 제제 투여 전 약 1 주 내지 최대 30 분 범위 내에서 제 1 제제의 투여를 포함한다. 사후 투여는 또한, 예를 들어, 제 2 제제의 투여 전 약 2 주 내지 최대 30분 범위 내의 제 1 제제의 투여를 포함할 수 있다. 이후 또는 나중 투여는, 예를 들어, 제 1 제제 투여 후 약 1 주 내지 최대 30분 범위 내에서 제 2 제제 투여를 포함한다. 이후 또는 나중의 투여는 또한, 예를 들어, 제 1 제제 투여 후 약 2 주 내지 최대 30분 범위 내에서 제 2 제제의 투여를 포함할 수 있다.
본 발명은 MYH7B의 억제제, 제 2 치료제 및 약학적으로 허용가능한 담체 또는 부형제를 포함하는 약학적 조성물을 포함한다. 특정 실시태양에서, 약학적 조성물은 MYH7B의 둘 이상의 억제제를 포함할 수 있다. 일부 실시태양에서, 제 2 치료제는 miR-208a, miR-208b, miR-499, miR-15a, miR-15b, miR-16, miR-195 또는 이들의 조합의 안티센스 올리고뉴클레오티드 억제제와 같은 심장 치료제이다. 이런 실시태양에서, 제 2 치료제는 MYH7B의 억제제와 동일한 제제 또는 별도의 제제에 포함될 수 있다. 임상 적용이 고려되는 경우, 약학적 조성물은 의도된 용도에 적합한 형태로 제조될 것이다. 일반적으로, 이것은 발열원뿐만 아니라 인간 또는 동물에게 해를 줄 수 있는 다른 불순물이 본질적으로 없는 조성물의 제조를 수반할 것이다.
거대분자 복합체, 나노캡슐, 미소구체, 비드, 및 수중유 에멀전, 미셀, 혼합 미셀, 및 리포솜을 포함하는 지질-기반 시스템과 같은 콜로이드 분산 시스템이 MYH7B의 올리고뉴클레오티드 억제제 또는 MYH7B 뉴클레오티드 억제제를 발현하는 구조체를 위한 전달 비히클로서 사용될 수 있다. 본 발명의 핵산을 심장 및 골격 근육 조직으로 전달하기에 적합한 상업적으로 구입가능한 지방 에멀전은 Intralipid®, Liposyn®, Liposyn®II, Liposyn®III, Nutrilipid, 및 다른 유사한 지질 에멀전을 포함한다. 생체내 전달 비히클로 사용하기 위한 바람직한 콜로이드 시스템은 리포솜(즉, 인공 막소포)이다. 이러한 시스템의 제조 및 사용은 당업계에 주지되어 있다. 예시적인 제제는 또한 전문이 본 발명에 참조로서 포함되는 US 5,981,505; US 6,217,900; US 6,383,512; US 5,783,565; US 7,202,227; US 6,379,965; US 6,127,170; US 5,837,533; US 6,747,014; 및 WO03/093449에서 개시된다.
특정 실시태양에서, 전달에 사용되는 리포솜은 미국 특허 출원 공개공보 제 20110076322호에 상세히 기술된 SMARTICLES®(Marina Biotech, Inc.)와 같은 친양쪽성 리포좀이다. SMARTICLES®의 표면 전하는 완전히 가역적이라서 이를 핵산 전달에 특히 적합하게 만든다. SMARTICLES®는 주사를 통해 전달되고, 안정적으로 유지되며, 핵산을 전달하기 위해 유리 세포 및 교차 세포막을 응집시킬 수 있다.
일부 실시태양에서, 적절한 염 및 버퍼는 전달 비히클을 안정하게 하고 표적 세포에 의한 흡수를 허용한다. 본 발명의 수용성 조성물은 약학적으로 허용 가능한 담체(carrier) 또는 수성 매질(aqueous medium)에 용해 또는 분산된 억제제 폴리뉴클레오티드(예를 들어, 리포솜 또는 다른 복합체 또는 발현 벡터)을 포함하는 유효량의 전달 비히클을 포함한다. "약학적으로 허용가능한" 또는 "약리학적으로 허용가능한"이란 문구는 동물 또는 사람에게 투여되었을 때, 해로운, 알레르기의, 또는 다른 뜻밖의(untoward) 반응들을 일으키지 않는 분자 독립체(molecular entities) 및 조성물을 나타낸다. 본 발명에 사용된 "약학적으로 허용가능한 담체"는 용매, 버퍼, 용액, 분산매, 코팅, 항균 및 항진균제, 등장성 및 흡수 지연제 및 인간에 투여하기 적합한 약과 같은 약의 제제화에 사용이 허용되는 다른 물질을 포함한다. 임의의 통상적인 매질 또는 제제가 본 발명의 활성 성분과 양립 불가능한 것을 제외하고는, 치료 조성물에서의 이의 사용이 고려된다. 약학적 활성 물질들을 위한 이와 같은 매질 및 제제의 사용은 당업계에 주지되어 있다. 보충적인 활성 성분들 또한 조성물에 혼합될 수 있다.
본 발명의 활성 조성물은 전형적인 약학 제제를 포함할 수 있다. 본 발명에 따른 이들 조성물의 투여는 표적 조직이 그 경로를 통해 이용 가능한 한 임의의 통상적인 경로를 통해 이루어질 수 있다. 여기에는 구강, 비강(흡입) 또는 협측이 포함된다. 선택적으로, 투여는 피내, 피하, 근육 내, 복강 내 또는 정맥 내 주사에 의해, 또는 심근 조직으로의 직접 주사에 의한 것일 수 있다. MYH7B 억제제 또는 MYH7B 억제제를 포함하는 발현 구조체를 포함하는 약학적 조성물은 치료제를 심장에 전달하기 위해 관상 순환을 분리하는 카테터 시스템 또는 시스템에 의해 투여될 수도 있다. 심장 및 관상 혈관계에 치료제를 전달하기 위한 다양한 카테터 시스템이 당업계에 공지되어 있다. 본 발명에서 사용하기에 적합한 카테터-기반 전달 방법 또는 관상 격리 방법의 일부 비 제한적인 예들은 전문이 본 발명에 참조로서 포함되는 미국특허 6,416,510; 미국특허 6,716,196; 미국특허 6,953,466, WO 2005/082440, WO 2006/089340, 미국특허공보 2007/0203445, 미국특허공보 2006/0148742, 및 미국특허공보 2007/0060907에 개시된다. 이런 조성물은 일반적으로 본 발명에 기재된 바와 같은 약학적으로 허용가능한 조성물로서 투여될 것이다.
본 발명의 다른 실시태양에서, 본 발명에 기재된 MYH7B 억제제를 포함하는 조성물은 스텐트, 벌룬 또는 카테터와 같은 의료 장치용 코팅제로서 제제화될 수 있다. 대상에서 심장 질환을 치료하는 방법에 특히 유용하게, MYH7B의 억제제는 약물 스텐트를 제조하기 위해 금속 스텐트를 코팅하는데 사용될 수 있다. 약물 용출 스텐트는 협착된 또는 병에 걸린 동맥을 개방시켜 유지하고 화합물을 방출하여 세포 증식 및/또는 염증을 예방하기 위한 스캐폴드이다. MYH7B의 억제제는 억제제를 시간이 지남에 따라 방출하기 위해 얇은 중합체에 묻혀있는 금속 스텐트에 도포될 수 있다. 장치-기반 전달 방법 및 코팅 장치의 방법은 약물-용출 스텐트 및 다른 이식가능한 장치와 마찬가지로 당업계에 주지되어 있다. 예를 들어, 미국 특허 제 7,294,329호, 제 7,247,313호, 제 7,236,821호, 제 7,244,522호, 제 7,105,018호, 제 7,087,263호, 제 7,083,642호, 제 7,055,237호, 제 7,041,127호, 제 6,716,242호 및 제 6,589,286호 및 WO 2004/004602에 개시되어있다. 따라서, 본 발명은 MYH7B 억제제로 코팅된 벌룬, 카테터 또는 스텐트와 같은 의료 장치를 포함한다. 일부 실시태양에서, MYH7B 억제제는 약물-용출 스텐트에 혼입하기 위한 제제를 제조하기 위해 다른 치료제(예를 들어, 항 혈관재협착 화합물)와 조합하여 사용될 수 있다.
활성 화합물은 또한 비경구 또는 복강 내 투여될 수 있다. 예시로서, 유리 염기 또는 약리학적으로 허용가능한 염으로서 활성 화합물의 용액은 하이드록시프로필셀룰로오스와 같은 계면 활성제와 적절하게 혼합된 물에서 제조될 수 있다. 분산액은 또한 글리세롤, 액체 폴리에틸렌 글리콜 및 이들의 혼합물 및 오일에서 제조될 수 있다. 통상적인 보관 및 사용 조건하에서, 이들 제제는 일반적으로 미생물의 성장을 방지하기 위한 방부제를 함유한다.
주사용 또는 카테터 전달에 적합한 약학적 형태는, 예를 들어, 살균 수성 용액 또는 분산액 및 살균 주사 용액 또는 분산액의 즉석 제조를 위한 살균 분말을 포함한다. 일반적으로 이들 제제는 살균되며 쉬운 주입성이 존재할 정도로 유동성이다. 제제는 제조 및 보관 조건하에서 안정해야 하며 세균 및 균류와 같은 미생물의 오염 작용에 대비하여 보관되어야 한다. 적합한 용매 또는 분산매는 예를 들어, 물, 에탄올, 폴리올(예를 들어, 글리세롤, 프로필렌 글리콜, 및 액체 폴리에틸렌 글리콜 등), 이들의 적절한 혼합물, 및 식물 오일을 포함할 수 있다. 적절한 유동성은, 예를 들어, 레시틴과 같은 코팅제의 사용에 의해, 분산액의 경우에 필요한 입자 크기의 유지에 의해, 계면활성제의 사용에 의해 유지될 수 있다. 미생물 작용의 방지는 예를 들어, 파라벤, 클로로부탄올, 페놀, 소르빈산, 티메로살 등의 다양한 항균 및 항진균제에 의해 이루어질 수 있다. 많은 경우에서, 등장성 물질, 예를 들어, 당 또는 염화나트륨을 포함하는 것이 바람직할 것이다. 주사 가능한 조성물의 장기 흡수는 흡수 지연제, 예를 들어, 알루미늄 모노스테아레이트 및 젤라틴을 조성물에 사용하여 이루어질 수 있다.
살균 주사 용액은 적절한 양의 컨주게이트를 용매에 원하는 임의의 다른 성분(예를 들어, 상기에서 열거한 것)과 함께 혼합함으로써 제조될 수 있다. 일반적으로, 분산액은 다양한 살균 활성 성분들을 기본적인 분산매와 원하는 다른 성분들, 예를 들어 앞에서 열거한 것들을 포함하는 살균 비히클에 혼합함으로써 제조된다. 살균 주사 용액 제조를 위한 살균 분말의 경우, 바람직한 제조방법은 상기 살균-여과된 용액으로부터 어떠한 추가적으로 요구되는 성분들을 더한 활성 성분(들)의 파우더를 생산하는 진공-건조 및 동결-건조 기술을 포함한다.
본 발명의 조성물은 일반적으로 중성 또는 염 형태로 제제화될 수 있다. 약학적으로 허용가능한 염은, 예를 들어, 무기산(예를 들어, 염산 또는 인산) 또는 유기산(예를 들어, 아세트산, 옥살산, 타르타르산, 만델산 등)으로부터 유도된 산 부가 염(단백질의 유리 아미노기로 형성됨)을 포함한다. 단백질의 유리 카복실기로 형성된 염은 무기 염기(예를 들어, 나트륨, 칼륨, 암모늄, 칼슘 또는 수산화 제 2 철) 또는 유기 염기(예를 들어, 아이소프로필아민, 트라이메틸아민, 히스티딘, 프로카인 등)로부터 유도될 수 있다.
제제 시에, 용액들은 되도록 투약 제제에 적합한 방식 및 치료에 효과적인 양으로 투여된다. 제제는 주사 가능한 용액, 약물 방출 캡슐 등과 같은 다양한 투약 형태로 쉽게 투여될 수 있다. 수용액에서 비경구적 투여를 위해서, 예를 들어, 용액은 일반적으로 적절하게 완충되고, 액상 희석액은 먼저 예를 들어 충분한 식염수 또는 글루코스로 등장성을 만든다. 이러한 수용액은 예를 들어, 정맥내, 근육내, 피하 및 복막내 투여에 사용될 수 있다. 바람직하게는, 특히 본 명세서의 관점에서, 당업계의 통상적인 기술을 가진자에게 이미 알려진 바대로 살균 수성 매질이 사용된다. 예로써, 단일 복용량은 1ml의 등장성 NaCl 용액에 용해되고 1000ml의 피하주액 유체(hypodermoclysis fluid)에 첨가되거나 또는 예정된 주입 부위에 주사될 수 있다(예를 들어, "Remington's Pharmaceutical Sciences" 15th Edition, 페이지 1035-1038 및 1570-1580 참조). 치료받는 대상의 질환에 따라 용량의 일부 변화는 필연적으로 생기게 된다. 투여에 대해 책임을 지는 사람은 어떤 일이 있어도 개개의 대상을 위한 적합한 용량을 결정할 것이다. 또한, 인간 투여에 있어, 제제는 제제 당국에 의해 요구되는 살균성, 발열원성, 일반 안전 및 순도 기준을 만족해야만 한다.
본 발명의 특정 실시태양에서, 본 발명의 약학적 조성물은 투여용 장치와 함께 포장되거나 또는 투여용 장치 내에 저장된다. 주사 제제용 장치는 주사 포트, 자동 주사기, 주사 펌프 및 주사 펜을 포함하나 이에 제한되지 않는다. 에어로졸 또는 분말 제제용 장치는 흡입기, 흡입기, 흡인기 등을 포함하나 이에 제한되지 않는다. 따라서, 본 발명은 본 발명에 기술된 하나 이상의 장애를 치료 또는 예방하기 위한 본 발명의 약학적 조성물을 포함하는 투여 장치를 포함한다.
본 발명은 제한적으로 해석되지 않는 다음 추가 실시예에 의해 추가로 설명된다. 당업자는 본 발명의 관점에서 개시된 특정 실시태양에 여러 변화를 가할 수 있고 본 발명의 취지와 범위를 벗어나지 않고 유사하거나 동일한 결과를 여전히 얻을 수 있다는 것을 안다.
본 발명 전체에서 언급된 모든 특허 및 비 특허 문헌은 모든 목적을 위해 전문이 참조로 본 발명에 포함된다.
실시예 :
실시예 1: MYH7B의 억제는 MYH7을 하향 조절한다
인간 iPS 심근세포를 MYH7B를 표적으로 하는 대조군 올리고뉴클레오티드 또는 안티센스 올리고뉴클레오티드(Anti-7b #1(5'-GTGAATGCGGATGAA-3'; SEQ ID NO: 1) 및 Anti-7b #2(5'-GAAGTGGTAGTCATA-3'; SEQ ID NO: 2))로 형질감염시켰다. MYH7B 및 MYH7(β-MHC) mRNA의 수준은 실시간 PCR을 사용하여 48시간에 측정하였다. 갑상선 호르몬, T3로 치료된 인간 iPS 심근세포를 양성 대조군으로 사용하였다. T3는 β-MHC의 발현을 하향 조절하는 것으로 알려져 있다. 형질감염된 세포로부터 분리된 RNA의 실시간 PCR 분석은 MYH7B의 저해가 MYH7B뿐만 아니라 MYH7(β-MHC)의 하향 조절을 초래하였다는 것을 나타내었다. 예상한 대로, T3는 MYH7(β-MHC)을 하향 조절하였으나(도 1b) MYH7B 또는 miR-208a, miR-208b 및 miR-499의 수준에는 영향을 미치지 않았다(도 1a 및 2).
MYH7B의 넉다운이 마이오신 전환을 초래한다는 관찰은 부분적으로 마이오신의 인트론성 miRNA (MYH7B, miR-499; MYH7, miR-208b; MYH6, miR-208a)의 조절을 통해 일어날 수 있다. 따라서, 본 발명자는 인간 iPS 심근세포에서 MYH7B의 억제가 myomiRs, miR-208a, miR-208b 또는 miR-499의 발현에 영향을 주는지 여부를 테스트 하였다.
구체적으로, MYH7B의 하향 조절이 myomiRs(miR-208a, miR-499 및 miR-208b)의 발현에 어떠한 영향을 미치는지를 측정하기 위해, miR-208a, miR-499 및 miR-208b의 수준을 형질감염 48시간 후에 측정하였다. miR-208a, miR-499 또는 miR-208b의 발현에 현저한 효과는 관찰되지 않았다(도 2). 시간이 지남에 따라, MYH7의 하향 조절 때문에 miR-208b의 하향 조절이 있을 수 있으나, 도 2의 데이터는 MYH7B에 대한 안티센스 올리고뉴클레오티드가 직접적으로 또는 즉시 myomiRs의 발현에 영향을 미치지 않는 것을 나타낸다. 따라서, MYH7B의 억제에 의한 마이오신 전환의 조절은 심장 세포에서 신규한 miRNA 독립적인 매커니즘을 나타낸다.
miR-208a는 설치류에서 miR-499의 상류에 작용하고 출생 후의 miR-499, MYH7B 및 β-MHC 발현에 필요하다는 것이 밝혀졌다(van Rooji et al., "Control of stress-dependent cardiac growth and gene expression by a microRNA," Science, 2007, 316(5824), 575-579; Montgomery et al., "Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure," Circulation, 2011, 124(14), 1537-1547). miR-499와 MYH7B의 손실이 설치류의 심장에서 β-MHC 하향 조절에 필요하다(van Rooji et al., "A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance," Dev. Cell, 2009, 17, 662-673). 이 연구는 myomiR은 설치류와 같은 α-MHC 우성 종에서 β-MHC 발현의 조절에 중요한 역할을 한다는 것을 나타내지만, 돼지, 토끼 및 인간과 같은 β-MHC 우성 동물에서의 연구는 대체 매커니즘이 β-MHC 우성 동물에서 β-MHC의 발현을 조절하는데 관련될 수 있다는 것을 나타낸다.
실시예 2: 비대성 심근병증 환자로부터 유래된 iPS 심장 세포에서 MYH7B의 억제는 MYH7을 하향 조절한다
대조군iPS 심근세포 및 돌연변이 R663H를 갖는 비대성 심근병증(HCM) 환자로부터 유래된 iPS 심근세포를 대조군 올리고뉴클레오티드 또는 MYH7B 안티센스 올리고뉴클레오티드(Anti-7b # 1 및 Anti-7b # 2; SEQ ID NOs: 1 및 2)로 형질감염시켰다. 실시간 PCR을 사용하여 형질 감염 후 48시간 및 1주(168시간)에 MYH7(β-MHC) mRNA의 수준을 측정하였다. 실시간 PCR 분석은 MYH7B의 억제가 HCM 심근세포에 MYH7(β-MHC) 발현의 하향 조절을 초래한다는 것을 나타내었다(도 3a). 또한, MYH7(β-MHC)의 발현의 하향 조절은 치료 후 1 주까지 지속되었다(도 3b).
실시예 3: MYH7B의 억제는 β- MHC 단백질을 하향 조절한다
MYH7B의 억제가 단백질 수준에서 MYH7의 하향 조절을 초래하는지를 측정하기 위해 대조군 및 HCM R663H 인간 iPS 심근세포를 대조 올리고뉴클레오티드, MYH7B ASO #1(SEQ ID NO: 1), MYH7B ASO 및 TINY로 형질감염시켰다. TINY는 miR-208a, miR-208b 및 miR-499의 씨드 영역에 상보적인 8mer 올리고이다. MYH7(β-MHC) 단백질의 수준은 웨스턴 블럿 분석에 의해 평가되었다. 결과는 MYH7B 안티센스 올리고뉴클레오티드를 사용하는 대조군 또는 HCM iPS 심근세포의 치료가 치료 후 96시간에서 MYH7(β-MHC) 단백질을 현저하게 하향 조절하였다는 것을 나타내었다(도 4). 대조군 올리고는 효과를 나타내지 않았다. T3를 양성 대조군으로 사용하였다.
실시예 4 : MYH7B에 대한 안티센스 올리고뉴클레오티드( ASOs )의 스크리닝
인간 iPS 심근세포를 대조 올리고뉴클레오티드(모조(Mock)) 또는 MYH7B를 표적으로 하는 1.5 nM의 테스트 ASO로 형질감염시켰다. MYH7B mRNA의 수준은 실시간 PCR을 사용하여 48시간에 측정하였다(도 5). 다수의 ASO는 MYH7B 수준의 50% 초과 억제를 나타냈다. 특히, 하기 ASO 화합물을 테스트하였다:
CPD # SEQ ID NO:
Comp-1 SEQ ID NO: 52
Comp-2 SEQ ID NO: 8
Comp-3 SEQ ID NO: 22
Comp-4 SEQ ID NO: 82
Comp-5 SEQ ID NO: 96
Comp-6 SEQ ID NO: 110
Comp-7 SEQ ID NO: 3
Comp-8 SEQ ID NO: 140
Comp-9 SEQ ID NO: 154
Comp-10 SEQ ID NO: 170
Comp-11 SEQ ID NO: 38
Comp-12 SEQ ID NO: 54
Comp-13 SEQ ID NO: 24
Comp-14 SEQ ID NO: 68
Comp-15 SEQ ID NO: 84
Comp-16 SEQ ID NO: 98
Comp-17 SEQ ID NO: 112
Comp-18 SEQ ID NO: 126
Comp-19 SEQ ID NO: 142
Comp-20 SEQ ID NO: 156
Comp-21 SEQ ID NO: 172
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Comp-32 SEQ ID NO: 174
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Comp-34 SEQ ID NO: 58
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Comp-37 SEQ ID NO: 72
Comp-38 SEQ ID NO: 88
Comp-39 SEQ ID NO: 102
Comp-40 SEQ ID NO: 116
Comp-41 SEQ ID NO: 130
Comp-42 SEQ ID NO: 146
Comp-43 SEQ ID NO: 160
Comp-44 SEQ ID NO: 176
Comp-45 SEQ ID NO: 44
Comp-46 SEQ ID NO: 60
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Comp-49 SEQ ID NO: 74
Comp-50 SEQ ID NO: 90
Comp-51 SEQ ID NO: 104
Comp-52 SEQ ID NO: 118
Comp-53 SEQ ID NO: 132
Comp-54 SEQ ID NO: 148
Comp-55 SEQ ID NO: 162
Comp-56 SEQ ID NO: 178
Comp-57 SEQ ID NO: 46
Comp-58 SEQ ID NO: 62
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Comp-60 SEQ ID NO: 32
Comp-61 SEQ ID NO: 76
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Comp-63 SEQ ID NO: 3
Comp-64 SEQ ID NO: 120
Comp-65 SEQ ID NO: 134
Comp-66 SEQ ID NO: 150
Comp-67 SEQ ID NO: 164
Comp-68 SEQ ID NO: 180
Comp-69 SEQ ID NO: 48
Comp-70 SEQ ID NO: 64
Comp-71 SEQ ID NO: 18
Comp-72 SEQ ID NO: 34
Comp-73 SEQ ID NO: 78
Comp-74 SEQ ID NO: 106
Comp-75 SEQ ID NO: 122
Comp-76 SEQ ID NO: 136
Comp-77 SEQ ID NO: 152
Comp-78 SEQ ID NO: 166
Comp-79 SEQ ID NO: 182
Comp-80 SEQ ID NO: 50
Comp-81 SEQ ID NO: 66
Comp-82 SEQ ID NO: 36
Comp-83 SEQ ID NO: 80
Comp-84 SEQ ID NO: 94
Comp-85 SEQ ID NO: 108
Comp-86 SEQ ID NO: 124
Comp-87 SEQ ID NO: 138
Comp-88 SEQ ID NO: 168
실시예 5 : ASO의 수동적 투여시 MYH7B의 억제
실시예 4에서 MYH7B 수준의 50% 초과의 억제를 나타내는 ASO는 수동적 섭취시 이들의 억제 가능성에 대해 추가로 테스트하였다. 구체적으로, 선택된 ASO를 1, 5 또는 10μM ASO 농도에서 168시간 동안 인간 iPS 심근세포와 함께 배양하였다. MYH7B, MYH7(β-MHC) 및 MYH6(α-MHC) mRNA의 수준은 실시간 PCR을 사용하여 168시간에 측정하였다. 실시간 PCR 분석은 많은 ASO가 MYH7B mRNA 수준을 하향 조절하였다는 것을 나타내었다(도 6a). 또한, SEQ ID NO: 146의 서열을 갖는 안티센스 올리고뉴클레오티드는 마이오신의 수준에서 "전환"을 나타내었고, 여기서 MYH7B의 억제 후에 β-MHC가 하향 조절되고 α-MHC가 상향 조절된다(도 6b 및 6c). 일부 다른 ASO는 또한 β-및 α-MHC 수준에서 유사한 경향을 나타내었다(도 6b 및 6c).
SEQ ID NO: 146의 서열을 갖는 또 다른 ASO 화합물을 또한 수동적 섭취시 억제 활성에 대해 테스트하였다. 인간 iPS 심근세포를 SEQ ID NO: 146의 화합물 5 μM과 함께 168시간 동안 배양하고, 실시간 PCR을 사용하여 MYH7B, MYH7(β-MHC) 및 MYH6(α-MHC) mRNA의 수준을 측정하였다. 도 7에 도시된 바오 같이, SEQ ID NO: 146을 갖는 화합물은 또한 마이오신의 수준에서 "전환"을 나타내었고, 여기서 β-MHC는 MYH7B의 억제 후에 β-MHC가 하향 조절되고 α-MHC가 상향 조절된다.
실시예 6 : 테스트 ASO의 생체내 활성
MYH7B의 생체외 억제를 나타내는 ASO를 이들의 생체내 억제 잠재성에 대해 추가로 테스트하였다. 구체적으로, 선택된 ASO를 3일 연속 하루 당 25mg/kg의 용량으로 쥐에 피하 주사하였고, 최종 투여 48시간 후 쥐를 희생시켰다. 쥐의 좌심실에서 MYH7B mRNA의 수준을 실시간 PCR을 사용하여 측정하였다(도 8). 도 8에 도시된 바와 같이, 수동적 투여(예를 들어, SEQ ID NO: 146)를 통해 강력한 활성을 나타낸 안티센스 올리고뉴클레오티드 화합물은 생체 내에서 MYH7B의 하향 조절을 나타내지만, 수동적 투여(예를 들어, SEQ ID NO: 32)를 통해 활성을 나타내지 않는 화합물 또한 생체내에서 활성을 나타내지 않았다.
쥐에서 강력한 활성을 나타낸 SEQ ID NO: 146 및 148의 서열을 갖는 화합물을 β-MHC 우성 종에서의 평가를 위한 토끼 연구에 대해 선택하였다. 토끼에게 1일, 3일, 5일, 10일 및 17일에 SEQ ID NO: 146 및 148을 갖는 화합물 10, 15, 20 또는 25mg/kg을 피하 주사하고 18일에 희생시켰다. MYH7B에 대한 실시간 PCR 데이터는 두 심실 모두에서 MYH7B의 용량-의존성 감소를 나타낸다(도 9a-9b). 또한, MYH7B(5003)의 가장 강력한 억제를 가진 토끼는 β-MHC(MYH7)에서 가장 강력한 감소를 나타내었다. 도 9c 및 9d 참조.
실시예 7 : MYH7B ASO의 활성에 대한 뉴클레오티드 변형의 영향
SEQ ID NO: 146의 ASO 화합물을 다양한 위치에서 변형시켜 그의 활성에 대한 변형의 효과를 평가하였다. 변형은 LNA 뉴클레오티드를 상응하는 ENA 뉴클레오티드 및 다른 염기 및 당 변형으로 대체하는 것을 포함한다. 도 10a는 LNA에 대한 ENA의 치환이 MYH7B를 표적으로 하는 수동적 활성을 유지하였다는 것을 나타낸다. 마찬가지로, 시티딘의 5'-메틸 시티딘에 의한 치환 및 LNA 염기의 2'O-메틸 변형 뉴클레오티드에 의한 치환은 활성을 보유한다(도 10b). 도 10c는 주쇄 변형이 화합물의 수동적 활성에 크게 영향을 준다는 것을 나타낸다.
실시예 8: 추가 ASO의 스크리닝
추가의 안티센스 올리고뉴클레오티드 화합물을 수동적 투여시 이들의 억제 가능성에 대해 스크리닝하였다. 인간 iPS 심근세포를 48시간 동안 테스트 화합물 5μM로 수동적으로 치료하였다. MYH7B mRNA의 수준은 실시간 PCR을 사용하여 48시간에 측정하였다. 다수의 ASO는 MYH7B 수준의 강력한 억제를 나타내었지만 다른 화합물은 MYH7B 수준에 영향을 나타내지 않았다. 도 11a 내지도 11d는 4개의 개별적인 연구 결과를 나타낸다. 특히, 다음 ASO 화합물을 테스트하였다.
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SEQUENCE LISTING <110> Miragen Therapeutics, Inc. Montgomery, Rusty Dalby, Christina <120> INHIBITORS OF MYH7B AND USES THEREOF <130> MIRG-046/01WO 308934-2479 <150> US 62/033,018 <151> 2014-08-04 <160> 792 <170> PatentIn version 3.5 <210> 1 <211> 15 <212> DNA <213> Homo sapiens <400> 1 gtgaatgcgg atgaa 15 <210> 2 <211> 15 <212> DNA <213> Homo sapiens <400> 2 gaagtggtag tcata 15 <210> 3 <211> 15 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(15) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (15)..(15) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 3 gtgaatgcgg atgaa 15 <210> 4 <211> 14 <212> DNA <213> Homo sapiens <400> 4 gaggccaaga tcaa 14 <210> 5 <211> 14 <212> DNA <213> Homo sapiens <400> 5 tggaggagct gcag 14 <210> 6 <211> 6602 <212> DNA <213> Homo sapiens <400> 6 taggcttaaa gagcaggcgg ggcagagacc catacctttg gcgctgagtc gaggccagga 60 aggggcggtc gatgagaggg cggccttagc attaggagtg cgtcggctgc accctggcgg 120 atggaccttg ggaaggaggg gaggggacca tcggggtcgg cggggagcta cgggttcccc 180 tcttccaaga cgggtgccaa gtgatgagta tcaggtgtct atggtgagat ttggggagga 240 tcccagacct taacagccct ttggttgaaa cctctcacaa tgtggcagag atggggtttt 300 gatgtgttgc ccaggctggt cttgaactcc tgagcttaag tgatgtgtcc gcctgggcct 360 cccaaagtgc tggaattaca gacatgagtg gcaataaaag gggtagcaga gcttcctgcc 420 ctcaccgtgg tgccgagtgc ctgctgcctt gggccgcctt gaacctccag ggtttccagc 480 tcctcctcct tcaccccagt gccactgcca tgatggatgt gagtgaactt ggggagtctg 540 cccgctacct ccgccagggc taccaggaga tgacgaaggt gcacactatc ccatgggacg 600 ggaagaagcg agtctgggtg cctgatgaac aggacgccta cgtggaggcc gaggtcaagt 660 cggaggctac cgggggcaga gtcaccgtgg agaccaaaga ccagaaggtg ctgatggtgc 720 gtgaagccga gctgcagccc atgaacccgc ctcgcttcga cttactggag gacatggcca 780 tgatgacgca cctgaacgag gcctctgtgc tgcacaacct gcgccagcgc tatgcccgct 840 ggatgatcta tacctactca ggcctcttct gtgtcaccat caacccctac aaatggctcc 900 cagtctatac ggcctccgta gtggctgctt acaagggaaa gcgccgctca gattccccgc 960 cccatatata tgcggtggcg gacaacgcct acaacgacat gctgcgcaac cgagacaacc 1020 agtccatgct gatcaccgga gagtcggggg ccggtaagac ggttaacacc aagcgggtca 1080 ttcagtactt tgccatcgtc gctgccctgg gagacgggcc gggcaagaag gcccaatttc 1140 tggcaacaaa gacggggggc acccttgagg atcaaatcat cgaggccaac cctgccatgg 1200 aggcctttgg caacgccaag accctgagga atgataactc ctcccgcttt ggcaagttca 1260 tccgcattca ctttggtccc tctgggaagc tggcatccgc ggatattgac agctatctcc 1320 tggagaagtc gcgggtgatc ttccagttgc ctggtgagcg cagctaccat gtctactacc 1380 agatcctctc agggaggaag ccagagctgc aggacatgct gcttctgtct atgaacccct 1440 atgactacca cttctgcagc cagggcgtca tcaccgtgga caacatgaat gatggggagg 1500 agctcatcgc caccgaccat gccatggaca tcctaggctt cagcgtggat gagaaatgtg 1560 cctgctataa gatcgtgggc gccctcctgc actttggcaa catgaagttc aagcagaagc 1620 agcgggagga gcaggcggag gccgatggca ctgagagtgc tgacaaggct gcctacctga 1680 tgggggtcag cagtggggac ctcctcaaag gccttttgca cccccgggtg cgtgtaggga 1740 acgagtacgt gaccaagggc cagagtgtgg agcaggtggt gtttgctgtg ggggctctgg 1800 ccaaggccac ctatgaccgg ctgttcaggt ggctggtgtc tcggatcaac cagaccctgg 1860 acacaaagct gccccggcag ttcttcatcg gggttctgga catcgctggg tttgagatct 1920 ttgagttcaa cagcttcgaa cagctgtgca tcaacttcac caatgagaaa ttgcagcagt 1980 tcttcaacca gcacatgttt gtgctggagc aggaggagta caagcgggag ggcatcgact 2040 gggtcttcat cgacttcggc cttgacctgc agccttgcat cgacctcatc gagaagccac 2100 tgggcatcct gtccatcctg gaggaggaat gcatgttccc caaggcctca gacgccagct 2160 tccgggccaa gctctacgac aaccacgcgg ggaagtcacc caatttccag cagcctcggc 2220 ctgacaagaa gcgcaagtac caggcccact tcgaggtggt ccactacgca ggcgtggtgc 2280 cttacagcat tgtgggctgg ctggagaaaa acaaggatcc cctgaatgag accgtggtcc 2340 ccatcttcca gaagtcacag aataggctcc tggcgactct ctatgagaat tatgcgggct 2400 cctgctccac tgagcccccc aagtctgggg tgaaagagaa gcgtaagaag gcagcatcgt 2460 tccagacggt gtcccagctg cacaaggaga acctcaacaa gctgatgacc aacctgcggg 2520 ccacacagcc ccacttcgtc cgctgcattg tccccaacga gaacaaaacc ccaggggtca 2580 tggatgcctt cttggtgcta caccagctgc gctgcaatgg ggtcctggag gggatccgga 2640 tctgccgcca agggttcccc aacaggttgc tctacaccga cttccggcag cggtaccgta 2700 tcctgaaccc cagtgccatc ccggatgaca ccttcatgga cagcaggaag gccacagaga 2760 aactgctggg ctcgctggac ttggatcaca cccagtacca gtttggccac accaaggtgt 2820 tcttcaaggc tgggcttcta ggcgtcctgg aagagctccg tgaccagcgc ctggccaagg 2880 tgctgacgct gctgcaggcg cggagccgtg gccgcctcat gcgccttgag taccagcgcc 2940 tgctgggagg cagggatgcg ctgttcacca tccagtggaa catccgtgcc ttcaatgccg 3000 tcaagaactg gtcatggatg aagctctttt tcaagatgaa gccgctgctg cgctcggcgc 3060 aggctgagga ggagctggcg gccctgcggg cagagctgcg ggggttgcga ggggcgctgg 3120 ctgcggccga ggccaagcgc caggaactgg aggagacgca cgtcagcatc acccaggaga 3180 agaatgacct ggccctgcag ctgcaggctg agcaggacaa cctggcagat gccgaggagc 3240 gctgccactt gctgatcaag tccaaggtgc agctggaggg gaaggtgaag gagctgagtg 3300 agcggctgga ggatgaggag gaggtgaacg ctgacctggc cgcccgccgg cgcaagctgg 3360 aggacgagtg cacggagctc aagaaggaca ttgatgacct ggagctgaca ctggccaaag 3420 ctgagaagga gaagcaagcc actgagaaca aggtgaagaa cctgacggaa gagatggctg 3480 cgctggacga gtcagtggcc cggctgacca aggagaagaa ggcgttgcag gaggcccacc 3540 aacaggccct gggtgacctg caggccgagg aggaccgtgt gagcgcgctg accaaggcca 3600 agctccggct ggagcaacag gtggaggacc tggaatgctc cctggagcag gagaagaagc 3660 tgcgcatgga cacggagcgg gccaagcgca agctggaggg tgacctgaag ctgacgcagg 3720 agtcggtggc tgatgctgct caagacaagc agcagctgga ggagaagctc aagaagaagg 3780 actccgagct gagccagctg agcctgcggg tggaagacga gcagctcttg ggggcccaga 3840 tgcagaagaa gatcaaggag ctgcaggctc gggcggagga gctggaagag gagctggagg 3900 cagagcgggc agcccgggcc cgcgtggaga agcagcgtgc agaggcggcg cgggagctgg 3960 aggagctgag cgagcggctg gaggaggcag gcggcgcatc cgcggggcag cgcgagggct 4020 gccgcaagcg ggaggcggag ctggggaggc tgcggcggga gctggaggag gcggcgctgc 4080 ggcacgaggc cacagtggcg gcactgcggc gcaagcaggc ggagggcgcg gcggagctgg 4140 gggagcaggt ggacagcctg cagcgggtgc ggcagaagct ggagaaggag aagagtgagc 4200 tgcgcatgga ggtggacgac ctggctgcca acgtggagac tctgacccgc gccaaggcca 4260 gtgcagagaa gctgtgccgg acctatgagg atcagctaag cgaggccaag atcaaggtgg 4320 aggagctgca gcggcagctg gcggacgcaa gcacgcagcg tgggcgacta cagacggaaa 4380 gcggggagct gagtcgcctg ctagaggaga aggagtgtct gatcagtcag ctgagccgtg 4440 gaaaggccct ggccgcccaa agcctggaag agttgcggcg ccagctagag gaggaaagca 4500 aggccaagag tgccctggcc cacgccgtgc aggctctgcg gcacgactgt gacctcctgc 4560 gggagcaaca cgaggaggag gctgaggccc aggctgagct gcagcggctg ctgtccaagg 4620 ccaatgccga ggtggcccag tggaggagca agtacgaagc agatgccatc cagaggaccg 4680 aggagctgga ggaggccaaa aaaaagctgg cactgcggct gcaggaggca gaggagggcg 4740 tggaggctgc caacgccaag tgctcatcgt tggagaaggc caagctgcgg ctacagacag 4800 agtcagagga tgtaaccctg gagctggagc gggcgacctc agcagctgct gcgctggaca 4860 agaagcagcg gcacttggaa cgggcactgg aggaacggcg gcggcaggag gaggagatgc 4920 agcgggagct ggaggcggca cagagggagt cccgtggcct gggcaccgag ctcttccggc 4980 tgcggcacgg ccacgaggag gcacttgaag ccctggagac gctcaagcgg gagaacaaga 5040 acctgcagga ggagatcagc gacctcacag accaggtgag tctcagtggg aagagcatcc 5100 aggaactgga gaaaaccaag aaggcgctgg aaggcgagaa gagtgagatc caggctgcac 5160 tggaggaggc agagggggcc ctggagctgg aggagaccaa gacgctgcgg atccagctgg 5220 agctctccca ggtcaaagca gaagtggacc ggaagctggc agagaaagac gaggagtgcg 5280 ctaacctgag gcgcaaccac cagcgagctg tggagtccct gcaggcctcc ctggatgcag 5340 agacacgggc ccgcaatgag gcgctgcggc tcaagaagaa gatggagggt gacctcaacg 5400 acctggagct gcagctgggc catgccaccc gtcaggccac agaggcccag gctgccacgc 5460 ggctgatgca ggcacagctc aaggaggagc aggcagggcg ggacgaggag cagcggctgg 5520 cagctgagct ccacgagcag gcgcaggctc tggagcgccg ggcctcgctg ctggctgcgg 5580 agctggagga gctgcgggct gccctggagc agggcgagcg cagccggcga ctggcagagc 5640 aggagctttt ggaggccacc gagcgcctca accttctgca ttcgcagaac acaggcctcc 5700 taaaccagaa gaagaagctg gaggcggact tggcccagct gagcggggag gtggaggagg 5760 ctgcacagga gaggcgggag gctgaggaga aggccaaaaa ggccatcact gatgcggcca 5820 tgatggccga ggagctgaag aaggagcagg acacaagtgc acacctggaa cggatgaaga 5880 agacgctgga gcagacggtg cgcgagctcc aggcccgcct tgaggaggca gaacaggccg 5940 ccctccgtgg cgggaagaag caggtgcaga agctggaggc caaggtacgg gagctggagg 6000 ctgagcttga tgcagagcag aagaagcacg ccgaggccct taagggcgtg cgcaagcatg 6060 agcgccgtgt caaggagctc gcataccagg ccgaggagga caggaagaac ctggctcgca 6120 tgcaggacct ggtggacaag ctgcagagca aggtcaagag ctacaagcgc cagtttgagg 6180 aggcggagca gcaggccaac accaacctgg ccaagtatcg caaggcccag cacgagctgg 6240 atgatgcgga ggagcgggca gacatggcgg aaacccaggc caacaagctg cgggcacgga 6300 cccgggacgc cctgggcccc aagcacaagg agtgacggcc tgaccccctg ggctctaaag 6360 aggaatgtct gctgttgcac atctggctga ggccacctgc cccgatcctg ccatctctgc 6420 atcgccccct gctgccttca gccttccctg ggccctgaat aaacaccaca gccagtttcc 6480 ttctcattct tttctttggg gttcaggagg aaaaacacag tcctagggac aaaagccagg 6540 tccacagcag tcatttttaa aataaagtta tttaatagtc tccaaaaaaa aaaaaaaaaa 6600 aa 6602 <210> 7 <211> 14 <212> DNA <213> Homo sapiens <400> 7 gttcatgggc tgca 14 <210> 8 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 8 gttcatgggc tgca 14 <210> 9 <211> 14 <212> DNA <213> Homo sapiens <400> 9 ggttcatggg ctgc 14 <210> 10 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 10 ggttcatggg ctgc 14 <210> 11 <211> 14 <212> DNA <213> Homo sapiens <400> 11 gggttcatgg gctg 14 <210> 12 <211> 14 <212> DNA <213> Artificial Sequence <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 12 gggttcatgg gctg 14 <210> 13 <211> 14 <212> DNA <213> Homo sapiens <400> 13 atggtgacac agaa 14 <210> 14 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 14 atggtgacac agaa 14 <210> 15 <211> 14 <212> DNA <213> Homo sapiens <400> 15 atcagcatgg actg 14 <210> 16 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 16 atcagcatgg actg 14 <210> 17 <211> 14 <212> DNA <213> Homo sapiens <400> 17 gcttggtgtt aacc 14 <210> 18 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 18 gcttggtgtt aacc 14 <210> 19 <211> 14 <212> DNA <213> Homo sapiens <400> 19 tccatggcag ggtt 14 <210> 20 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 20 tccatggcag ggtt 14 <210> 21 <211> 14 <212> DNA <213> Homo sapiens <400> 21 ctccatggca gggt 14 <210> 22 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 22 ctccatggca gggt 14 <210> 23 <211> 14 <212> DNA <213> Homo sapiens <400> 23 cctccatggc aggg 14 <210> 24 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 24 cctccatggc aggg 14 <210> 25 <211> 14 <212> DNA <213> Homo sapiens <400> 25 gcctccatgg cagg 14 <210> 26 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 26 gcctccatgg cagg 14 <210> 27 <211> 14 <212> DNA <213> Homo sapiens <400> 27 agatagctgt caat 14 <210> 28 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 28 agatagctgt caat 14 <210> 29 <211> 14 <212> DNA <213> Homo sapiens <400> 29 gagatagctg tcaa 14 <210> 30 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 30 gagatagctg tcaa 14 <210> 31 <211> 14 <212> DNA <213> Homo sapiens <400> 31 ggagatagct gtca 14 <210> 32 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 32 ggagatagct gtca 14 <210> 33 <211> 14 <212> DNA <213> Homo sapiens <400> 33 aggagatagc tgtc 14 <210> 34 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 34 aggagatagc tgtc 14 <210> 35 <211> 14 <212> DNA <213> Homo sapiens <400> 35 caggagatag ctgt 14 <210> 36 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 36 caggagatag ctgt 14 <210> 37 <211> 14 <212> DNA <213> Homo sapiens <400> 37 ccaggagata gctg 14 <210> 38 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 38 ccaggagata gctg 14 <210> 39 <211> 14 <212> DNA <213> Homo sapiens <400> 39 tccaggagat agct 14 <210> 40 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 40 tccaggagat agct 14 <210> 41 <211> 14 <212> DNA <213> Homo sapiens <400> 41 cagaagtggt agtc 14 <210> 42 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 42 cagaagtggt agtc 14 <210> 43 <211> 14 <212> DNA <213> Homo sapiens <400> 43 tgcagaagtg gtag 14 <210> 44 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 44 tgcagaagtg gtag 14 <210> 45 <211> 14 <212> DNA <213> Homo sapiens <400> 45 ctgcagaagt ggta 14 <210> 46 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 46 ctgcagaagt ggta 14 <210> 47 <211> 14 <212> DNA <213> Homo sapiens <400> 47 gcactctcag tgcc 14 <210> 48 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 48 gcactctcag tgcc 14 <210> 49 <211> 14 <212> DNA <213> Homo sapiens <400> 49 taggcagcct tgtc 14 <210> 50 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 50 taggcagcct tgtc 14 <210> 51 <211> 14 <212> DNA <213> Homo sapiens <400> 51 acactctggc cctt 14 <210> 52 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 52 acactctggc cctt 14 <210> 53 <211> 14 <212> DNA <213> Homo sapiens <400> 53 tccacactct ggcc 14 <210> 54 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 54 tccacactct ggcc 14 <210> 55 <211> 14 <212> DNA <213> Homo sapiens <400> 55 ctccacactc tggc 14 <210> 56 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 56 ctccacactc tggc 14 <210> 57 <211> 14 <212> DNA <213> Homo sapiens <400> 57 gctccacact ctgg 14 <210> 58 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 58 gctccacact ctgg 14 <210> 59 <211> 14 <212> DNA <213> Homo sapiens <400> 59 tgctccacac tctg 14 <210> 60 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 60 tgctccacac tctg 14 <210> 61 <211> 14 <212> DNA <213> Homo sapiens <400> 61 acctgctcca cact 14 <210> 62 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 62 acctgctcca cact 14 <210> 63 <211> 14 <212> DNA <213> Homo sapiens <400> 63 ccacctgctc caca 14 <210> 64 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 64 ccacctgctc caca 14 <210> 65 <211> 14 <212> DNA <213> Homo sapiens <400> 65 accacctgct ccac 14 <210> 66 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 66 accacctgct ccac 14 <210> 67 <211> 14 <212> DNA <213> Homo sapiens <400> 67 ctcaaagatc tcaa 14 <210> 68 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 68 ctcaaagatc tcaa 14 <210> 69 <211> 14 <212> DNA <213> Homo sapiens <400> 69 actcaaagat ctca 14 <210> 70 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 70 actcaaagat ctca 14 <210> 71 <211> 14 <212> DNA <213> Homo sapiens <400> 71 aactcaaaga tctc 14 <210> 72 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 72 aactcaaaga tctc 14 <210> 73 <211> 14 <212> DNA <213> Homo sapiens <400> 73 atgaagaccc agtc 14 <210> 74 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 74 atgaagaccc agtc 14 <210> 75 <211> 14 <212> DNA <213> Homo sapiens <400> 75 gatgaagacc cagt 14 <210> 76 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 76 gatgaagacc cagt 14 <210> 77 <211> 14 <212> DNA <213> Homo sapiens <400> 77 tagtggacca cctc 14 <210> 78 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 78 tagtggacca cctc 14 <210> 79 <211> 14 <212> DNA <213> Homo sapiens <400> 79 aggttctcct tgtg 14 <210> 80 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 80 aggttctcct tgtg 14 <210> 81 <211> 14 <212> DNA <213> Homo sapiens <400> 81 gaggttctcc ttgt 14 <210> 82 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 82 gaggttctcc ttgt 14 <210> 83 <211> 14 <212> DNA <213> Homo sapiens <400> 83 tgaggttctc cttg 14 <210> 84 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 84 tgaggttctc cttg 14 <210> 85 <211> 14 <212> DNA <213> Homo sapiens <400> 85 ttgaggttct cctt 14 <210> 86 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 86 ttgaggttct cctt 14 <210> 87 <211> 14 <212> DNA <213> Homo sapiens <400> 87 gttgaggttc tcct 14 <210> 88 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 88 gttgaggttc tcct 14 <210> 89 <211> 14 <212> DNA <213> Homo sapiens <400> 89 cttgttgagg ttct 14 <210> 90 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 90 cttgttgagg ttct 14 <210> 91 <211> 14 <212> DNA <213> Homo sapiens <400> 91 gggctgtgtg gccc 14 <210> 92 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 92 gggctgtgtg gccc 14 <210> 93 <211> 14 <212> DNA <213> Homo sapiens <400> 93 ccttcctgct gtcc 14 <210> 94 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 94 ccttcctgct gtcc 14 <210> 95 <211> 14 <212> DNA <213> Homo sapiens <400> 95 ggccttcctg ctgt 14 <210> 96 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 96 ggccttcctg ctgt 14 <210> 97 <211> 14 <212> DNA <213> Homo sapiens <400> 97 tggatggtga acag 14 <210> 98 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 98 tggatggtga acag 14 <210> 99 <211> 14 <212> DNA <213> Homo sapiens <400> 99 ctggatggtg aaca 14 <210> 100 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 100 ctggatggtg aaca 14 <210> 101 <211> 14 <212> DNA <213> Homo sapiens <400> 101 cactggatgg tgaa 14 <210> 102 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 102 cactggatgg tgaa 14 <210> 103 <211> 14 <212> DNA <213> Homo sapiens <400> 103 tccactggat ggtg 14 <210> 104 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 104 tccactggat ggtg 14 <210> 105 <211> 14 <212> DNA <213> Homo sapiens <400> 105 ttccactgga tggt 14 <210> 106 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 106 ttccactgga tggt 14 <210> 107 <211> 14 <212> DNA <213> Homo sapiens <400> 107 tgcagggcca ggtc 14 <210> 108 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 108 tgcagggcca ggtc 14 <210> 109 <211> 14 <212> DNA <213> Homo sapiens <400> 109 ctgcagggcc aggt 14 <210> 110 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 110 ctgcagggcc aggt 14 <210> 111 <211> 14 <212> DNA <213> Homo sapiens <400> 111 accttggact tgat 14 <210> 112 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 112 accttggact tgat 14 <210> 113 <211> 14 <212> DNA <213> Homo sapiens <400> 113 gcaccttgga cttg 14 <210> 114 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 114 gcaccttgga cttg 14 <210> 115 <211> 14 <212> DNA <213> Homo sapiens <400> 115 tgcaccttgg actt 14 <210> 116 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 116 tgcaccttgg actt 14 <210> 117 <211> 14 <212> DNA <213> Homo sapiens <400> 117 ctgcaccttg gact 14 <210> 118 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 118 ctgcaccttg gact 14 <210> 119 <211> 14 <212> DNA <213> Homo sapiens <400> 119 gctgcacctt ggac 14 <210> 120 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 120 gctgcacctt ggac 14 <210> 121 <211> 14 <212> DNA <213> Homo sapiens <400> 121 agctgcacct tgga 14 <210> 122 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 122 agctgcacct tgga 14 <210> 123 <211> 14 <212> DNA <213> Homo sapiens <400> 123 ctgcactggc cttg 14 <210> 124 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 124 ctgcactggc cttg 14 <210> 125 <211> 14 <212> DNA <213> Homo sapiens <400> 125 tctgcactgg cctt 14 <210> 126 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 126 tctgcactgg cctt 14 <210> 127 <211> 14 <212> DNA <213> Homo sapiens <400> 127 ctctgcactg gcct 14 <210> 128 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 128 ctctgcactg gcct 14 <210> 129 <211> 14 <212> DNA <213> Homo sapiens <400> 129 tctctgcact ggcc 14 <210> 130 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 130 tctctgcact ggcc 14 <210> 131 <211> 14 <212> DNA <213> Homo sapiens <400> 131 ttctctgcac tggc 14 <210> 132 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 132 ttctctgcac tggc 14 <210> 133 <211> 14 <212> DNA <213> Homo sapiens <400> 133 cttctctgca ctgg 14 <210> 134 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 134 cttctctgca ctgg 14 <210> 135 <211> 14 <212> DNA <213> Homo sapiens <400> 135 gcttctctgc actg 14 <210> 136 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 136 gcttctctgc actg 14 <210> 137 <211> 14 <212> DNA <213> Homo sapiens <400> 137 agcttctctg cact 14 <210> 138 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 138 agcttctctg cact 14 <210> 139 <211> 14 <212> DNA <213> Homo sapiens <400> 139 cagcttctct gcac 14 <210> 140 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 140 cagcttctct gcac 14 <210> 141 <211> 14 <212> DNA <213> Homo sapiens <400> 141 acagcttctc tgca 14 <210> 142 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 142 acagcttctc tgca 14 <210> 143 <211> 14 <212> DNA <213> Homo sapiens <400> 143 cacagcttct ctgc 14 <210> 144 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 144 cacagcttct ctgc 14 <210> 145 <211> 14 <212> DNA <213> Homo sapiens <400> 145 ttgatcttgg cctc 14 <210> 146 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 146 ttgatcttgg cctc 14 <210> 147 <211> 14 <212> DNA <213> Homo sapiens <400> 147 ctgcagctcc tcca 14 <210> 148 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 148 ctgcagctcc tcca 14 <210> 149 <211> 14 <212> DNA <213> Homo sapiens <400> 149 tgcctcctgc agcc 14 <210> 150 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 150 tgcctcctgc agcc 14 <210> 151 <211> 14 <212> DNA <213> Homo sapiens <400> 151 agcttggcct tctc 14 <210> 152 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 152 agcttggcct tctc 14 <210> 153 <211> 14 <212> DNA <213> Homo sapiens <400> 153 tctcctcctc ctgc 14 <210> 154 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 154 tctcctcctc ctgc 14 <210> 155 <211> 14 <212> DNA <213> Homo sapiens <400> 155 aggttcttcc tgtc 14 <210> 156 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 156 aggttcttcc tgtc 14 <210> 157 <211> 14 <212> DNA <213> Homo sapiens <400> 157 ccaggttctt cctg 14 <210> 158 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 158 ccaggttctt cctg 14 <210> 159 <211> 14 <212> DNA <213> Homo sapiens <400> 159 gccaggttct tcct 14 <210> 160 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 160 gccaggttct tcct 14 <210> 161 <211> 14 <212> DNA <213> Homo sapiens <400> 161 agccaggttc ttcc 14 <210> 162 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 162 agccaggttc ttcc 14 <210> 163 <211> 14 <212> DNA <213> Homo sapiens <400> 163 gagccaggtt cttc 14 <210> 164 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 164 gagccaggtt cttc 14 <210> 165 <211> 14 <212> DNA <213> Homo sapiens <400> 165 gaccttgctc tgca 14 <210> 166 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 166 gaccttgctc tgca 14 <210> 167 <211> 14 <212> DNA <213> Homo sapiens <400> 167 tgaccttgct ctgc 14 <210> 168 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 168 tgaccttgct ctgc 14 <210> 169 <211> 14 <212> DNA <213> Homo sapiens <400> 169 ttgaccttgc tctg 14 <210> 170 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 170 ttgaccttgc tctg 14 <210> 171 <211> 14 <212> DNA <213> Homo sapiens <400> 171 tcttgacctt gctc 14 <210> 172 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 172 tcttgacctt gctc 14 <210> 173 <211> 14 <212> DNA <213> Homo sapiens <400> 173 agctcttgac cttg 14 <210> 174 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 174 agctcttgac cttg 14 <210> 175 <211> 14 <212> DNA <213> Homo sapiens <400> 175 gtagctcttg acct 14 <210> 176 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 176 gtagctcttg acct 14 <210> 177 <211> 14 <212> DNA <213> Homo sapiens <400> 177 gtgctgggcc ttgc 14 <210> 178 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 178 gtgctgggcc ttgc 14 <210> 179 <211> 14 <212> DNA <213> Homo sapiens <400> 179 ttgttggcct gggt 14 <210> 180 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 180 ttgttggcct gggt 14 <210> 181 <211> 14 <212> DNA <213> Homo sapiens <400> 181 cagcttgttg gcct 14 <210> 182 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 182 cagcttgttg gcct 14 <210> 183 <211> 14 <212> DNA <213> Homo sapiens <400> 183 tcactcacat ccat 14 <210> 184 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 184 tcactcacat ccat 14 <210> 185 <211> 14 <212> DNA <213> Homo sapiens <400> 185 ttcactcaca tcca 14 <210> 186 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 186 ttcactcaca tcca 14 <210> 187 <211> 14 <212> DNA <213> Homo sapiens <400> 187 gttcactcac atcc 14 <210> 188 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 188 gttcactcac atcc 14 <210> 189 <211> 14 <212> DNA <213> Homo sapiens <400> 189 agttcactca catc 14 <210> 190 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 190 agttcactca catc 14 <210> 191 <211> 14 <212> DNA <213> Homo sapiens <400> 191 aagttcactc acat 14 <210> 192 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 192 aagttcactc acat 14 <210> 193 <211> 14 <212> DNA <213> Homo sapiens <400> 193 caagttcact caca 14 <210> 194 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 194 caagttcact caca 14 <210> 195 <211> 14 <212> DNA <213> Homo sapiens <400> 195 ccaagttcac tcac 14 <210> 196 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 196 ccaagttcac tcac 14 <210> 197 <211> 14 <212> DNA <213> Homo sapiens <400> 197 cccaagttca ctca 14 <210> 198 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 198 cccaagttca ctca 14 <210> 199 <211> 14 <212> DNA <213> Homo sapiens <400> 199 ccccaagttc actc 14 <210> 200 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 200 ccccaagttc actc 14 <210> 201 <211> 14 <212> DNA <213> Homo sapiens <400> 201 tccccaagtt cact 14 <210> 202 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 202 tccccaagtt cact 14 <210> 203 <211> 14 <212> DNA <213> Homo sapiens <400> 203 ctccccaagt tcac 14 <210> 204 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 204 ctccccaagt tcac 14 <210> 205 <211> 14 <212> DNA <213> Homo sapiens <400> 205 actccccaag ttca 14 <210> 206 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 206 actccccaag ttca 14 <210> 207 <211> 14 <212> DNA <213> Homo sapiens <400> 207 gactccccaa gttc 14 <210> 208 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 208 gactccccaa gttc 14 <210> 209 <211> 14 <212> DNA <213> Homo sapiens <400> 209 agactcccca agtt 14 <210> 210 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 210 agactcccca agtt 14 <210> 211 <211> 14 <212> DNA <213> Homo sapiens <400> 211 cagactcccc aagt 14 <210> 212 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 212 cagactcccc aagt 14 <210> 213 <211> 14 <212> DNA <213> Homo sapiens <400> 213 gcagactccc caag 14 <210> 214 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 214 gcagactccc caag 14 <210> 215 <211> 14 <212> DNA <213> Homo sapiens <400> 215 aggcacccag actc 14 <210> 216 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 216 aggcacccag actc 14 <210> 217 <211> 14 <212> DNA <213> Homo sapiens <400> 217 caggcaccca gact 14 <210> 218 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 218 caggcaccca gact 14 <210> 219 <211> 14 <212> DNA <213> Homo sapiens <400> 219 tcaggcaccc agac 14 <210> 220 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 220 tcaggcaccc agac 14 <210> 221 <211> 14 <212> DNA <213> Homo sapiens <400> 221 atcaggcacc caga 14 <210> 222 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 222 atcaggcacc caga 14 <210> 223 <211> 14 <212> DNA <213> Homo sapiens <400> 223 gctgcagaag tggt 14 <210> 224 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 224 gctgcagaag tggt 14 <210> 225 <211> 14 <212> DNA <213> Homo sapiens <400> 225 atgtccatgg catg 14 <210> 226 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 226 atgtccatgg catg 14 <210> 227 <211> 14 <212> DNA <213> Homo sapiens <400> 227 atcttatagc aggc 14 <210> 228 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 228 atcttatagc aggc 14 <210> 229 <211> 14 <212> DNA <213> Homo sapiens <400> 229 actctcagtg ccat 14 <210> 230 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 230 actctcagtg ccat 14 <210> 231 <211> 14 <212> DNA <213> Homo sapiens <400> 231 cactctcagt gcca 14 <210> 232 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 232 cactctcagt gcca 14 <210> 233 <211> 14 <212> DNA <213> Homo sapiens <400> 233 agcactctca gtgc 14 <210> 234 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 234 agcactctca gtgc 14 <210> 235 <211> 14 <212> DNA <213> Homo sapiens <400> 235 cagcactctc agtg 14 <210> 236 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 236 cagcactctc agtg 14 <210> 237 <211> 14 <212> DNA <213> Homo sapiens <400> 237 tcagcactct cagt 14 <210> 238 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 238 tcagcactct cagt 14 <210> 239 <211> 14 <212> DNA <213> Homo sapiens <400> 239 gtcagcactc tcag 14 <210> 240 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 240 gtcagcactc tcag 14 <210> 241 <211> 14 <212> DNA <213> Homo sapiens <400> 241 tgtcagcact ctca 14 <210> 242 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 242 tgtcagcact ctca 14 <210> 243 <211> 14 <212> DNA <213> Homo sapiens <400> 243 ccttgtcagc actc 14 <210> 244 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 244 ccttgtcagc actc 14 <210> 245 <211> 14 <212> DNA <213> Homo sapiens <400> 245 cactgctgac cccc 14 <210> 246 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 246 cactgctgac cccc 14 <210> 247 <211> 14 <212> DNA <213> Homo sapiens <400> 247 ccactgctga cccc 14 <210> 248 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 248 ccactgctga cccc 14 <210> 249 <211> 14 <212> DNA <213> Homo sapiens <400> 249 cccactgctg accc 14 <210> 250 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 250 cccactgctg accc 14 <210> 251 <211> 14 <212> DNA <213> Homo sapiens <400> 251 ccccactgct gacc 14 <210> 252 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 252 ccccactgct gacc 14 <210> 253 <211> 14 <212> DNA <213> Homo sapiens <400> 253 tccccactgc tgac 14 <210> 254 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 254 tccccactgc tgac 14 <210> 255 <211> 14 <212> DNA <213> Homo sapiens <400> 255 gtccccactg ctga 14 <210> 256 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 256 gtccccactg ctga 14 <210> 257 <211> 14 <212> DNA <213> Homo sapiens <400> 257 ggtccccact gctg 14 <210> 258 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 258 ggtccccact gctg 14 <210> 259 <211> 14 <212> DNA <213> Homo sapiens <400> 259 aggtccccac tgct 14 <210> 260 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 260 aggtccccac tgct 14 <210> 261 <211> 14 <212> DNA <213> Homo sapiens <400> 261 gaggtcccca ctgc 14 <210> 262 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 262 gaggtcccca ctgc 14 <210> 263 <211> 14 <212> DNA <213> Homo sapiens <400> 263 ggaggtcccc actg 14 <210> 264 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 264 ggaggtcccc actg 14 <210> 265 <211> 14 <212> DNA <213> Homo sapiens <400> 265 aggaggtccc cact 14 <210> 266 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 266 aggaggtccc cact 14 <210> 267 <211> 14 <212> DNA <213> Homo sapiens <400> 267 gaggaggtcc ccac 14 <210> 268 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 268 gaggaggtcc ccac 14 <210> 269 <211> 14 <212> DNA <213> Homo sapiens <400> 269 tgaggaggtc ccca 14 <210> 270 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 270 tgaggaggtc ccca 14 <210> 271 <211> 14 <212> DNA <213> Homo sapiens <400> 271 tttgaggagg tccc 14 <210> 272 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 272 tttgaggagg tccc 14 <210> 273 <211> 14 <212> DNA <213> Homo sapiens <400> 273 aaggcctttg agga 14 <210> 274 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 274 aaggcctttg agga 14 <210> 275 <211> 14 <212> DNA <213> Homo sapiens <400> 275 gcaaacacca cctg 14 <210> 276 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 276 gcaaacacca cctg 14 <210> 277 <211> 14 <212> DNA <213> Homo sapiens <400> 277 agcaaacacc acct 14 <210> 278 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 278 agcaaacacc acct 14 <210> 279 <211> 14 <212> DNA <213> Homo sapiens <400> 279 cagcaaacac cacc 14 <210> 280 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 280 cagcaaacac cacc 14 <210> 281 <211> 14 <212> DNA <213> Homo sapiens <400> 281 acagcaaaca ccac 14 <210> 282 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 282 acagcaaaca ccac 14 <210> 283 <211> 14 <212> DNA <213> Homo sapiens <400> 283 agacaccagc cacc 14 <210> 284 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 284 agacaccagc cacc 14 <210> 285 <211> 14 <212> DNA <213> Homo sapiens <400> 285 gagacaccag ccac 14 <210> 286 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 286 gagacaccag ccac 14 <210> 287 <211> 14 <212> DNA <213> Homo sapiens <400> 287 cttcttgtca ggcc 14 <210> 288 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 288 cttcttgtca ggcc 14 <210> 289 <211> 14 <212> DNA <213> Homo sapiens <400> 289 aagtgggcct ggta 14 <210> 290 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 290 aagtgggcct ggta 14 <210> 291 <211> 14 <212> DNA <213> Homo sapiens <400> 291 gtagtggacc acct 14 <210> 292 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 292 gtagtggacc acct 14 <210> 293 <211> 14 <212> DNA <213> Homo sapiens <400> 293 gcatccatga cccc 14 <210> 294 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 294 gcatccatga cccc 14 <210> 295 <211> 14 <212> DNA <213> Homo sapiens <400> 295 ggcatccatg accc 14 <210> 296 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 296 ggcatccatg accc 14 <210> 297 <211> 14 <212> DNA <213> Homo sapiens <400> 297 aggcatccat gacc 14 <210> 298 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 298 aggcatccat gacc 14 <210> 299 <211> 14 <212> DNA <213> Homo sapiens <400> 299 aaggcatcca tgac 14 <210> 300 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 300 aaggcatcca tgac 14 <210> 301 <211> 14 <212> DNA <213> Homo sapiens <400> 301 tgatcctcat aggt 14 <210> 302 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 302 tgatcctcat aggt 14 <210> 303 <211> 14 <212> DNA <213> Homo sapiens <400> 303 ctgatcctca tagg 14 <210> 304 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 304 ctgatcctca tagg 14 <210> 305 <211> 14 <212> DNA <213> Homo sapiens <400> 305 gctgatcctc atag 14 <210> 306 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 306 gctgatcctc atag 14 <210> 307 <211> 14 <212> DNA <213> Homo sapiens <400> 307 agctgatcct cata 14 <210> 308 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 308 agctgatcct cata 14 <210> 309 <211> 14 <212> DNA <213> Homo sapiens <400> 309 accttgatct tggc 14 <210> 310 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 310 accttgatct tggc 14 <210> 311 <211> 14 <212> DNA <213> Homo sapiens <400> 311 atggcatctg cttc 14 <210> 312 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 312 atggcatctg cttc 14 <210> 313 <211> 14 <212> DNA <213> Homo sapiens <400> 313 gatggcatct gctt 14 <210> 314 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 314 gatggcatct gctt 14 <210> 315 <211> 14 <212> DNA <213> Homo sapiens <400> 315 tctggatggc atct 14 <210> 316 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 316 tctggatggc atct 14 <210> 317 <211> 14 <212> DNA <213> Homo sapiens <400> 317 accttgctct gcag 14 <210> 318 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 318 accttgctct gcag 14 <210> 319 <211> 14 <212> DNA <213> Homo sapiens <400> 319 aggcagcagg cact 14 <210> 320 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 320 aggcagcagg cact 14 <210> 321 <211> 14 <212> DNA <213> Homo sapiens <400> 321 aaggcagcag gcac 14 <210> 322 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 322 aaggcagcag gcac 14 <210> 323 <211> 14 <212> DNA <213> Homo sapiens <400> 323 caaggcagca ggca 14 <210> 324 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 324 caaggcagca ggca 14 <210> 325 <211> 14 <212> DNA <213> Homo sapiens <400> 325 ccaaggcagc aggc 14 <210> 326 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 326 ccaaggcagc aggc 14 <210> 327 <211> 14 <212> DNA <213> Homo sapiens <400> 327 ggtgaaggag gagg 14 <210> 328 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 328 ggtgaaggag gagg 14 <210> 329 <211> 14 <212> DNA <213> Homo sapiens <400> 329 gggtgaagga ggag 14 <210> 330 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 330 gggtgaagga ggag 14 <210> 331 <211> 14 <212> DNA <213> Homo sapiens <400> 331 tcacatccat catg 14 <210> 332 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 332 tcacatccat catg 14 <210> 333 <211> 14 <212> DNA <213> Homo sapiens <400> 333 actcacatcc atca 14 <210> 334 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 334 actcacatcc atca 14 <210> 335 <211> 14 <212> DNA <213> Homo sapiens <400> 335 cactcacatc catc 14 <210> 336 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 336 cactcacatc catc 14 <210> 337 <211> 14 <212> DNA <213> Homo sapiens <400> 337 ttcatcaggc accc 14 <210> 338 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 338 ttcatcaggc accc 14 <210> 339 <211> 14 <212> DNA <213> Homo sapiens <400> 339 gttcatcagg cacc 14 <210> 340 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 340 gttcatcagg cacc 14 <210> 341 <211> 14 <212> DNA <213> Homo sapiens <400> 341 gtcctgttca tcag 14 <210> 342 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 342 gtcctgttca tcag 14 <210> 343 <211> 14 <212> DNA <213> Homo sapiens <400> 343 tggtctttgg tctc 14 <210> 344 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 344 tggtctttgg tctc 14 <210> 345 <211> 14 <212> DNA <213> Homo sapiens <400> 345 ttgtgcagca caga 14 <210> 346 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 346 ttgtgcagca caga 14 <210> 347 <211> 14 <212> DNA <213> Homo sapiens <400> 347 gttgtgcagc acag 14 <210> 348 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 348 gttgtgcagc acag 14 <210> 349 <211> 14 <212> DNA <213> Homo sapiens <400> 349 gactgggagc catt 14 <210> 350 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 350 gactgggagc catt 14 <210> 351 <211> 14 <212> DNA <213> Homo sapiens <400> 351 agactgggag ccat 14 <210> 352 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 352 agactgggag ccat 14 <210> 353 <211> 14 <212> DNA <213> Homo sapiens <400> 353 gtctcccagg gcag 14 <210> 354 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 354 gtctcccagg gcag 14 <210> 355 <211> 14 <212> DNA <213> Homo sapiens <400> 355 ctcagggtct tggc 14 <210> 356 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 356 ctcagggtct tggc 14 <210> 357 <211> 14 <212> DNA <213> Homo sapiens <400> 357 cctcagggtc ttgg 14 <210> 358 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 358 cctcagggtc ttgg 14 <210> 359 <211> 14 <212> DNA <213> Homo sapiens <400> 359 tcctcagggt cttg 14 <210> 360 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 360 tcctcagggt cttg 14 <210> 361 <211> 14 <212> DNA <213> Homo sapiens <400> 361 attcctcagg gtct 14 <210> 362 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 362 attcctcagg gtct 14 <210> 363 <211> 14 <212> DNA <213> Homo sapiens <400> 363 cattcctcag ggtc 14 <210> 364 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 364 cattcctcag ggtc 14 <210> 365 <211> 14 <212> DNA <213> Homo sapiens <400> 365 atcattcctc aggg 14 <210> 366 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 366 atcattcctc aggg 14 <210> 367 <211> 14 <212> DNA <213> Homo sapiens <400> 367 gttatcattc ctca 14 <210> 368 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 368 gttatcattc ctca 14 <210> 369 <211> 14 <212> DNA <213> Homo sapiens <400> 369 agttatcatt cctc 14 <210> 370 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 370 agttatcatt cctc 14 <210> 371 <211> 14 <212> DNA <213> Homo sapiens <400> 371 agggaccaaa gtga 14 <210> 372 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 372 agggaccaaa gtga 14 <210> 373 <211> 14 <212> DNA <213> Homo sapiens <400> 373 cccagaggga ccaa 14 <210> 374 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 374 cccagaggga ccaa 14 <210> 375 <211> 14 <212> DNA <213> Homo sapiens <400> 375 tcccagaggg acca 14 <210> 376 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 376 tcccagaggg acca 14 <210> 377 <211> 14 <212> DNA <213> Homo sapiens <400> 377 ttcccagagg gacc 14 <210> 378 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 378 ttcccagagg gacc 14 <210> 379 <211> 14 <212> DNA <213> Homo sapiens <400> 379 cttcccagag ggac 14 <210> 380 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 380 cttcccagag ggac 14 <210> 381 <211> 14 <212> DNA <213> Homo sapiens <400> 381 gcttcccaga ggga 14 <210> 382 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 382 gcttcccaga ggga 14 <210> 383 <211> 14 <212> DNA <213> Homo sapiens <400> 383 agctgtcaat atcc 14 <210> 384 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 384 agctgtcaat atcc 14 <210> 385 <211> 14 <212> DNA <213> Homo sapiens <400> 385 tagctgtcaa tatc 14 <210> 386 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 386 tagctgtcaa tatc 14 <210> 387 <211> 14 <212> DNA <213> Homo sapiens <400> 387 atagctgtca atat 14 <210> 388 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 388 atagctgtca atat 14 <210> 389 <211> 14 <212> DNA <213> Homo sapiens <400> 389 gatagctgtc aata 14 <210> 390 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 390 gatagctgtc aata 14 <210> 391 <211> 14 <212> DNA <213> Homo sapiens <400> 391 ctgagaggat ctgg 14 <210> 392 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 392 ctgagaggat ctgg 14 <210> 393 <211> 14 <212> DNA <213> Homo sapiens <400> 393 cctgagagga tctg 14 <210> 394 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 394 cctgagagga tctg 14 <210> 395 <211> 14 <212> DNA <213> Homo sapiens <400> 395 agacagaagc agca 14 <210> 396 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 396 agacagaagc agca 14 <210> 397 <211> 14 <212> DNA <213> Homo sapiens <400> 397 tagacagaag cagc 14 <210> 398 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 398 tagacagaag cagc 14 <210> 399 <211> 14 <212> DNA <213> Homo sapiens <400> 399 atagacagaa gcag 14 <210> 400 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 400 atagacagaa gcag 14 <210> 401 <211> 14 <212> DNA <213> Homo sapiens <400> 401 catagacaga agca 14 <210> 402 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 402 catagacaga agca 14 <210> 403 <211> 14 <212> DNA <213> Homo sapiens <400> 403 tcatagacag aagc 14 <210> 404 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 404 tcatagacag aagc 14 <210> 405 <211> 14 <212> DNA <213> Homo sapiens <400> 405 ttcatagaca gaag 14 <210> 406 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 406 ttcatagaca gaag 14 <210> 407 <211> 14 <212> DNA <213> Homo sapiens <400> 407 gttcatagac agaa 14 <210> 408 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 408 gttcatagac agaa 14 <210> 409 <211> 14 <212> DNA <213> Homo sapiens <400> 409 ggttcataga caga 14 <210> 410 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 410 ggttcataga caga 14 <210> 411 <211> 14 <212> DNA <213> Homo sapiens <400> 411 gggttcatag acag 14 <210> 412 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 412 gggttcatag acag 14 <210> 413 <211> 14 <212> DNA <213> Homo sapiens <400> 413 ccccatcatt catg 14 <210> 414 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 414 ccccatcatt catg 14 <210> 415 <211> 14 <212> DNA <213> Homo sapiens <400> 415 ttatagcagg caca 14 <210> 416 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 416 ttatagcagg caca 14 <210> 417 <211> 14 <212> DNA <213> Homo sapiens <400> 417 cttatagcag gcac 14 <210> 418 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 418 cttatagcag gcac 14 <210> 419 <211> 14 <212> DNA <213> Homo sapiens <400> 419 tcttatagca ggca 14 <210> 420 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 420 tcttatagca ggca 14 <210> 421 <211> 14 <212> DNA <213> Homo sapiens <400> 421 gatcttatag cagg 14 <210> 422 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 422 gatcttatag cagg 14 <210> 423 <211> 14 <212> DNA <213> Homo sapiens <400> 423 aaagtgcagg aggg 14 <210> 424 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 424 aaagtgcagg aggg 14 <210> 425 <211> 14 <212> DNA <213> Homo sapiens <400> 425 ttgccaaagt gcag 14 <210> 426 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 426 ttgccaaagt gcag 14 <210> 427 <211> 14 <212> DNA <213> Homo sapiens <400> 427 aaaggccttt gagg 14 <210> 428 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 428 aaaggccttt gagg 14 <210> 429 <211> 14 <212> DNA <213> Homo sapiens <400> 429 aaaaggcctt tgag 14 <210> 430 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 430 aaaaggcctt tgag 14 <210> 431 <211> 14 <212> DNA <213> Homo sapiens <400> 431 caaaaggcct ttga 14 <210> 432 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 432 caaaaggcct ttga 14 <210> 433 <211> 14 <212> DNA <213> Homo sapiens <400> 433 gcaaaaggcc tttg 14 <210> 434 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 434 gcaaaaggcc tttg 14 <210> 435 <211> 14 <212> DNA <213> Homo sapiens <400> 435 tgcaaaaggc cttt 14 <210> 436 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 436 tgcaaaaggc cttt 14 <210> 437 <211> 14 <212> DNA <213> Homo sapiens <400> 437 gtgcaaaagg cctt 14 <210> 438 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 438 gtgcaaaagg cctt 14 <210> 439 <211> 14 <212> DNA <213> Homo sapiens <400> 439 ggtgcaaaag gcct 14 <210> 440 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 440 ggtgcaaaag gcct 14 <210> 441 <211> 14 <212> DNA <213> Homo sapiens <400> 441 gggtgcaaaa ggcc 14 <210> 442 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 442 gggtgcaaaa ggcc 14 <210> 443 <211> 14 <212> DNA <213> Homo sapiens <400> 443 gtcataggtg gcct 14 <210> 444 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 444 gtcataggtg gcct 14 <210> 445 <211> 14 <212> DNA <213> Homo sapiens <400> 445 ggtcataggt ggcc 14 <210> 446 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 446 ggtcataggt ggcc 14 <210> 447 <211> 14 <212> DNA <213> Homo sapiens <400> 447 ccacctgaac agcc 14 <210> 448 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 448 ccacctgaac agcc 14 <210> 449 <211> 14 <212> DNA <213> Homo sapiens <400> 449 gccacctgaa cagc 14 <210> 450 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 450 gccacctgaa cagc 14 <210> 451 <211> 14 <212> DNA <213> Homo sapiens <400> 451 gacaccagcc acct 14 <210> 452 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 452 gacaccagcc acct 14 <210> 453 <211> 14 <212> DNA <213> Homo sapiens <400> 453 tgtccagggt ctgg 14 <210> 454 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 454 tgtccagggt ctgg 14 <210> 455 <211> 14 <212> DNA <213> Homo sapiens <400> 455 gtgtccaggg tctg 14 <210> 456 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 456 gtgtccaggg tctg 14 <210> 457 <211> 14 <212> DNA <213> Homo sapiens <400> 457 tgtgtccagg gtct 14 <210> 458 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 458 tgtgtccagg gtct 14 <210> 459 <211> 14 <212> DNA <213> Homo sapiens <400> 459 tgggtgactt cccc 14 <210> 460 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 460 tgggtgactt cccc 14 <210> 461 <211> 14 <212> DNA <213> Homo sapiens <400> 461 ttgggtgact tccc 14 <210> 462 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 462 ttgggtgact tccc 14 <210> 463 <211> 14 <212> DNA <213> Homo sapiens <400> 463 attgggtgac ttcc 14 <210> 464 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 464 attgggtgac ttcc 14 <210> 465 <211> 14 <212> DNA <213> Homo sapiens <400> 465 gctggaaatt gggt 14 <210> 466 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 466 gctggaaatt gggt 14 <210> 467 <211> 14 <212> DNA <213> Homo sapiens <400> 467 ctgtaaggca ccac 14 <210> 468 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 468 ctgtaaggca ccac 14 <210> 469 <211> 14 <212> DNA <213> Homo sapiens <400> 469 gctgtaaggc acca 14 <210> 470 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 470 gctgtaaggc acca 14 <210> 471 <211> 14 <212> DNA <213> Homo sapiens <400> 471 tgctgtaagg cacc 14 <210> 472 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 472 tgctgtaagg cacc 14 <210> 473 <211> 14 <212> DNA <213> Homo sapiens <400> 473 attctgtgac ttct 14 <210> 474 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 474 attctgtgac ttct 14 <210> 475 <211> 14 <212> DNA <213> Homo sapiens <400> 475 tattctgtga cttc 14 <210> 476 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 476 tattctgtga cttc 14 <210> 477 <211> 14 <212> DNA <213> Homo sapiens <400> 477 ctattctgtg actt 14 <210> 478 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 478 ctattctgtg actt 14 <210> 479 <211> 14 <212> DNA <213> Homo sapiens <400> 479 cctattctgt gact 14 <210> 480 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 480 cctattctgt gact 14 <210> 481 <211> 14 <212> DNA <213> Homo sapiens <400> 481 gcctattctg tgac 14 <210> 482 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 482 gcctattctg tgac 14 <210> 483 <211> 14 <212> DNA <213> Homo sapiens <400> 483 agcctattct gtga 14 <210> 484 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 484 agcctattct gtga 14 <210> 485 <211> 14 <212> DNA <213> Homo sapiens <400> 485 gagcctattc tgtg 14 <210> 486 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 486 gagcctattc tgtg 14 <210> 487 <211> 14 <212> DNA <213> Homo sapiens <400> 487 ggagcctatt ctgt 14 <210> 488 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 488 ggagcctatt ctgt 14 <210> 489 <211> 14 <212> DNA <213> Homo sapiens <400> 489 aggagcctat tctg 14 <210> 490 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 490 aggagcctat tctg 14 <210> 491 <211> 14 <212> DNA <213> Homo sapiens <400> 491 caggagccta ttct 14 <210> 492 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 492 caggagccta ttct 14 <210> 493 <211> 14 <212> DNA <213> Homo sapiens <400> 493 ccaggagcct attc 14 <210> 494 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 494 ccaggagcct attc 14 <210> 495 <211> 14 <212> DNA <213> Homo sapiens <400> 495 gccaggagcc tatt 14 <210> 496 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 496 gccaggagcc tatt 14 <210> 497 <211> 14 <212> DNA <213> Homo sapiens <400> 497 tctcatagag agtc 14 <210> 498 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 498 tctcatagag agtc 14 <210> 499 <211> 14 <212> DNA <213> Homo sapiens <400> 499 ttctcataga gagt 14 <210> 500 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 500 ttctcataga gagt 14 <210> 501 <211> 14 <212> DNA <213> Homo sapiens <400> 501 tggagcagga gccc 14 <210> 502 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 502 tggagcagga gccc 14 <210> 503 <211> 14 <212> DNA <213> Homo sapiens <400> 503 gtggagcagg agcc 14 <210> 504 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 504 gtggagcagg agcc 14 <210> 505 <211> 14 <212> DNA <213> Homo sapiens <400> 505 tgctgccttc ttac 14 <210> 506 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 506 tgctgccttc ttac 14 <210> 507 <211> 14 <212> DNA <213> Homo sapiens <400> 507 atgctgcctt ctta 14 <210> 508 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 508 atgctgcctt ctta 14 <210> 509 <211> 14 <212> DNA <213> Homo sapiens <400> 509 gatgctgcct tctt 14 <210> 510 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 510 gatgctgcct tctt 14 <210> 511 <211> 14 <212> DNA <213> Homo sapiens <400> 511 agaaggcatc catg 14 <210> 512 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 512 agaaggcatc catg 14 <210> 513 <211> 14 <212> DNA <213> Homo sapiens <400> 513 aagaaggcat ccat 14 <210> 514 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 514 aagaaggcat ccat 14 <210> 515 <211> 14 <212> DNA <213> Homo sapiens <400> 515 caagaaggca tcca 14 <210> 516 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 516 caagaaggca tcca 14 <210> 517 <211> 14 <212> DNA <213> Homo sapiens <400> 517 caccaagaag gcat 14 <210> 518 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 518 caccaagaag gcat 14 <210> 519 <211> 14 <212> DNA <213> Homo sapiens <400> 519 gcaccaagaa ggca 14 <210> 520 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 520 gcaccaagaa ggca 14 <210> 521 <211> 14 <212> DNA <213> Homo sapiens <400> 521 tagcaccaag aagg 14 <210> 522 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 522 tagcaccaag aagg 14 <210> 523 <211> 14 <212> DNA <213> Homo sapiens <400> 523 gtagcaccaa gaag 14 <210> 524 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 524 gtagcaccaa gaag 14 <210> 525 <211> 14 <212> DNA <213> Homo sapiens <400> 525 tgtagcacca agaa 14 <210> 526 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 526 tgtagcacca agaa 14 <210> 527 <211> 14 <212> DNA <213> Homo sapiens <400> 527 gtgtagcacc aaga 14 <210> 528 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 528 gtgtagcacc aaga 14 <210> 529 <211> 14 <212> DNA <213> Homo sapiens <400> 529 ggtgtagcac caag 14 <210> 530 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 530 ggtgtagcac caag 14 <210> 531 <211> 14 <212> DNA <213> Homo sapiens <400> 531 tggtgtagca ccaa 14 <210> 532 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 532 tggtgtagca ccaa 14 <210> 533 <211> 14 <212> DNA <213> Homo sapiens <400> 533 gggatggcac tggg 14 <210> 534 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 534 gggatggcac tggg 14 <210> 535 <211> 14 <212> DNA <213> Homo sapiens <400> 535 gctgtccatg aagg 14 <210> 536 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 536 gctgtccatg aagg 14 <210> 537 <211> 14 <212> DNA <213> Homo sapiens <400> 537 gcctagaagc ccag 14 <210> 538 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 538 gcctagaagc ccag 14 <210> 539 <211> 14 <212> DNA <213> Homo sapiens <400> 539 ggcattgaag gcac 14 <210> 540 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 540 ggcattgaag gcac 14 <210> 541 <211> 14 <212> DNA <213> Homo sapiens <400> 541 acttgatcag caag 14 <210> 542 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 542 acttgatcag caag 14 <210> 543 <211> 14 <212> DNA <213> Homo sapiens <400> 543 gacttgatca gcaa 14 <210> 544 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 544 gacttgatca gcaa 14 <210> 545 <211> 14 <212> DNA <213> Homo sapiens <400> 545 gcattccagg tcct 14 <210> 546 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 546 gcattccagg tcct 14 <210> 547 <211> 14 <212> DNA <213> Homo sapiens <400> 547 agcattccag gtcc 14 <210> 548 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 548 agcattccag gtcc 14 <210> 549 <211> 14 <212> DNA <213> Homo sapiens <400> 549 ggagcattcc aggt 14 <210> 550 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 550 ggagcattcc aggt 14 <210> 551 <211> 14 <212> DNA <213> Homo sapiens <400> 551 gggagcattc cagg 14 <210> 552 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 552 gggagcattc cagg 14 <210> 553 <211> 14 <212> DNA <213> Homo sapiens <400> 553 cagggagcat tcca 14 <210> 554 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 554 cagggagcat tcca 14 <210> 555 <211> 14 <212> DNA <213> Homo sapiens <400> 555 caggctcagc tggc 14 <210> 556 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 556 caggctcagc tggc 14 <210> 557 <211> 14 <212> DNA <213> Homo sapiens <400> 557 gcaggctcag ctgg 14 <210> 558 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 558 gcaggctcag ctgg 14 <210> 559 <211> 14 <212> DNA <213> Homo sapiens <400> 559 gtcagagtct ccac 14 <210> 560 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 560 gtcagagtct ccac 14 <210> 561 <211> 14 <212> DNA <213> Homo sapiens <400> 561 ggtcagagtc tcca 14 <210> 562 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 562 ggtcagagtc tcca 14 <210> 563 <211> 14 <212> DNA <213> Homo sapiens <400> 563 gggtcagagt ctcc 14 <210> 564 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 564 gggtcagagt ctcc 14 <210> 565 <211> 14 <212> DNA <213> Homo sapiens <400> 565 ttagctgatc ctca 14 <210> 566 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 566 ttagctgatc ctca 14 <210> 567 <211> 14 <212> DNA <213> Homo sapiens <400> 567 cttagctgat cctc 14 <210> 568 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 568 cttagctgat cctc 14 <210> 569 <211> 14 <212> DNA <213> Homo sapiens <400> 569 atcagacact cctt 14 <210> 570 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 570 atcagacact cctt 14 <210> 571 <211> 14 <212> DNA <213> Homo sapiens <400> 571 tgatcagaca ctcc 14 <210> 572 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 572 tgatcagaca ctcc 14 <210> 573 <211> 14 <212> DNA <213> Homo sapiens <400> 573 ctgatcagac actc 14 <210> 574 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 574 ctgatcagac actc 14 <210> 575 <211> 14 <212> DNA <213> Homo sapiens <400> 575 actgatcaga cact 14 <210> 576 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 576 actgatcaga cact 14 <210> 577 <211> 14 <212> DNA <213> Homo sapiens <400> 577 gactgatcag acac 14 <210> 578 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 578 gactgatcag acac 14 <210> 579 <211> 14 <212> DNA <213> Homo sapiens <400> 579 tgactgatca gaca 14 <210> 580 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 580 tgactgatca gaca 14 <210> 581 <211> 14 <212> DNA <213> Homo sapiens <400> 581 ctgactgatc agac 14 <210> 582 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 582 ctgactgatc agac 14 <210> 583 <211> 14 <212> DNA <213> Homo sapiens <400> 583 gctgactgat caga 14 <210> 584 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 584 gctgactgat caga 14 <210> 585 <211> 14 <212> DNA <213> Homo sapiens <400> 585 agctgactga tcag 14 <210> 586 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 586 agctgactga tcag 14 <210> 587 <211> 14 <212> DNA <213> Homo sapiens <400> 587 ctcagctgac tgat 14 <210> 588 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 588 ctcagctgac tgat 14 <210> 589 <211> 14 <212> DNA <213> Homo sapiens <400> 589 gctcagctga ctga 14 <210> 590 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 590 gctcagctga ctga 14 <210> 591 <211> 14 <212> DNA <213> Homo sapiens <400> 591 ggctcagctg actg 14 <210> 592 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 592 ggctcagctg actg 14 <210> 593 <211> 14 <212> DNA <213> Homo sapiens <400> 593 tcctctgact ctgt 14 <210> 594 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 594 tcctctgact ctgt 14 <210> 595 <211> 14 <212> DNA <213> Homo sapiens <400> 595 atcctctgac tctg 14 <210> 596 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 596 atcctctgac tctg 14 <210> 597 <211> 14 <212> DNA <213> Homo sapiens <400> 597 catcctctga ctct 14 <210> 598 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 598 catcctctga ctct 14 <210> 599 <211> 14 <212> DNA <213> Homo sapiens <400> 599 acatcctctg actc 14 <210> 600 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 600 acatcctctg actc 14 <210> 601 <211> 14 <212> DNA <213> Homo sapiens <400> 601 tacatcctct gact 14 <210> 602 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 602 tacatcctct gact 14 <210> 603 <211> 14 <212> DNA <213> Homo sapiens <400> 603 ttacatcctc tgac 14 <210> 604 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 604 ttacatcctc tgac 14 <210> 605 <211> 14 <212> DNA <213> Homo sapiens <400> 605 gttacatcct ctga 14 <210> 606 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 606 gttacatcct ctga 14 <210> 607 <211> 14 <212> DNA <213> Homo sapiens <400> 607 ggttacatcc tctg 14 <210> 608 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 608 ggttacatcc tctg 14 <210> 609 <211> 14 <212> DNA <213> Homo sapiens <400> 609 gggttacatc ctct 14 <210> 610 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 610 gggttacatc ctct 14 <210> 611 <211> 14 <212> DNA <213> Homo sapiens <400> 611 agggttacat cctc 14 <210> 612 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 612 agggttacat cctc 14 <210> 613 <211> 14 <212> DNA <213> Homo sapiens <400> 613 cagggttaca tcct 14 <210> 614 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 614 cagggttaca tcct 14 <210> 615 <211> 14 <212> DNA <213> Homo sapiens <400> 615 ccagggttac atcc 14 <210> 616 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 616 ccagggttac atcc 14 <210> 617 <211> 14 <212> DNA <213> Homo sapiens <400> 617 gctccagggt taca 14 <210> 618 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 618 gctccagggt taca 14 <210> 619 <211> 14 <212> DNA <213> Homo sapiens <400> 619 agctccaggg ttac 14 <210> 620 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 620 agctccaggg ttac 14 <210> 621 <211> 14 <212> DNA <213> Homo sapiens <400> 621 gcagctgctg aggt 14 <210> 622 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 622 gcagctgctg aggt 14 <210> 623 <211> 14 <212> DNA <213> Homo sapiens <400> 623 agcagctgct gagg 14 <210> 624 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 624 agcagctgct gagg 14 <210> 625 <211> 14 <212> DNA <213> Homo sapiens <400> 625 cccttaaggg cctc 14 <210> 626 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 626 cccttaaggg cctc 14 <210> 627 <211> 14 <212> DNA <213> Homo sapiens <400> 627 aggcagcagg cact 14 <210> 628 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 628 aggcagcagg cact 14 <210> 629 <211> 14 <212> DNA <213> Homo sapiens <400> 629 tcactcacat ccat 14 <210> 630 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 630 tcactcacat ccat 14 <210> 631 <211> 14 <212> DNA <213> Homo sapiens <400> 631 actccccaag ttca 14 <210> 632 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 632 actccccaag ttca 14 <210> 633 <211> 14 <212> DNA <213> Homo sapiens <400> 633 aggcacccag actc 14 <210> 634 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 634 aggcacccag actc 14 <210> 635 <211> 14 <212> DNA <213> Homo sapiens <400> 635 gggttcatgg gctg 14 <210> 636 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 636 gggttcatgg gctg 14 <210> 637 <211> 14 <212> DNA <213> Homo sapiens <400> 637 atggtgacac agaa 14 <210> 638 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 638 atggtgacac agaa 14 <210> 639 <211> 14 <212> DNA <213> Homo sapiens <400> 639 atcagcatgg actg 14 <210> 640 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 640 atcagcatgg actg 14 <210> 641 <211> 14 <212> DNA <213> Homo sapiens <400> 641 gcttggtgtt aacc 14 <210> 642 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 642 gcttggtgtt aacc 14 <210> 643 <211> 14 <212> DNA <213> Homo sapiens <400> 643 tccatggcag ggtt 14 <210> 644 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 644 tccatggcag ggtt 14 <210> 645 <211> 14 <212> DNA <213> Homo sapiens <400> 645 agatagctgt caat 14 <210> 646 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 646 agatagctgt caat 14 <210> 647 <211> 14 <212> DNA <213> Homo sapiens <400> 647 cagaagtggt agtc 14 <210> 648 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 648 cagaagtggt agtc 14 <210> 649 <211> 14 <212> DNA <213> Homo sapiens <400> 649 gctgcagaag tggt 14 <210> 650 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 650 gctgcagaag tggt 14 <210> 651 <211> 14 <212> DNA <213> Homo sapiens <400> 651 atgtccatgg catg 14 <210> 652 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 652 atgtccatgg catg 14 <210> 653 <211> 14 <212> DNA <213> Homo sapiens <400> 653 atcttatagc aggc 14 <210> 654 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 654 atcttatagc aggc 14 <210> 655 <211> 14 <212> DNA <213> Homo sapiens <400> 655 gcactctcag tgcc 14 <210> 656 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 656 gcactctcag tgcc 14 <210> 657 <211> 14 <212> DNA <213> Homo sapiens <400> 657 taggcagcct tgtc 14 <210> 658 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 658 taggcagcct tgtc 14 <210> 659 <211> 14 <212> DNA <213> Homo sapiens <400> 659 tgaggaggtc ccca 14 <210> 660 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 660 tgaggaggtc ccca 14 <210> 661 <211> 14 <212> DNA <213> Homo sapiens <400> 661 acactctggc cctt 14 <210> 662 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 662 acactctggc cctt 14 <210> 663 <211> 14 <212> DNA <213> Homo sapiens <400> 663 acctgctcca cact 14 <210> 664 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 664 acctgctcca cact 14 <210> 665 <211> 14 <212> DNA <213> Homo sapiens <400> 665 agacaccagc cacc 14 <210> 666 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 666 agacaccagc cacc 14 <210> 667 <211> 14 <212> DNA <213> Homo sapiens <400> 667 ctcaaagatc tcaa 14 <210> 668 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 668 ctcaaagatc tcaa 14 <210> 669 <211> 14 <212> DNA <213> Homo sapiens <400> 669 atgaagaccc agtc 14 <210> 670 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 670 atgaagaccc agtc 14 <210> 671 <211> 14 <212> DNA <213> Homo sapiens <400> 671 cttcttgtca ggcc 14 <210> 672 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 672 cttcttgtca ggcc 14 <210> 673 <211> 14 <212> DNA <213> Homo sapiens <400> 673 tagtggacca cctc 14 <210> 674 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 674 tagtggacca cctc 14 <210> 675 <211> 14 <212> DNA <213> Homo sapiens <400> 675 aggttctcct tgtg 14 <210> 676 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 676 aggttctcct tgtg 14 <210> 677 <211> 14 <212> DNA <213> Homo sapiens <400> 677 gggctgtgtg gccc 14 <210> 678 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 678 gggctgtgtg gccc 14 <210> 679 <211> 14 <212> DNA <213> Homo sapiens <400> 679 ccttcctgct gtcc 14 <210> 680 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 680 ccttcctgct gtcc 14 <210> 681 <211> 14 <212> DNA <213> Homo sapiens <400> 681 tggatggtga acag 14 <210> 682 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 682 tggatggtga acag 14 <210> 683 <211> 14 <212> DNA <213> Homo sapiens <400> 683 tgcagggcca ggtc 14 <210> 684 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 684 tgcagggcca ggtc 14 <210> 685 <211> 14 <212> DNA <213> Homo sapiens <400> 685 accttggact tgat 14 <210> 686 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 686 accttggact tgat 14 <210> 687 <211> 14 <212> DNA <213> Homo sapiens <400> 687 gcattccagg tcct 14 <210> 688 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 688 gcattccagg tcct 14 <210> 689 <211> 14 <212> DNA <213> Homo sapiens <400> 689 gcaggctcag ctgg 14 <210> 690 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 690 gcaggctcag ctgg 14 <210> 691 <211> 14 <212> DNA <213> Homo sapiens <400> 691 ctgcactggc cttg 14 <210> 692 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 692 ctgcactggc cttg 14 <210> 693 <211> 14 <212> DNA <213> Homo sapiens <400> 693 gcttctctgc actg 14 <210> 694 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 694 gcttctctgc actg 14 <210> 695 <211> 14 <212> DNA <213> Homo sapiens <400> 695 ttgatcttgg cctc 14 <210> 696 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 696 ttgatcttgg cctc 14 <210> 697 <211> 14 <212> DNA <213> Homo sapiens <400> 697 ctgcagctcc tcca 14 <210> 698 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 698 ctgcagctcc tcca 14 <210> 699 <211> 14 <212> DNA <213> Homo sapiens <400> 699 tgactgatca gaca 14 <210> 700 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 700 tgactgatca gaca 14 <210> 701 <211> 14 <212> DNA <213> Homo sapiens <400> 701 atggcatctg cttc 14 <210> 702 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 702 atggcatctg cttc 14 <210> 703 <211> 14 <212> DNA <213> Homo sapiens <400> 703 tgcctcctgc agcc 14 <210> 704 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 704 tgcctcctgc agcc 14 <210> 705 <211> 14 <212> DNA <213> Homo sapiens <400> 705 agcttggcct tctc 14 <210> 706 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 706 agcttggcct tctc 14 <210> 707 <211> 14 <212> DNA <213> Homo sapiens <400> 707 ttacatcctc tgac 14 <210> 708 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 708 ttacatcctc tgac 14 <210> 709 <211> 14 <212> DNA <213> Homo sapiens <400> 709 agcagctgct gagg 14 <210> 710 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 710 agcagctgct gagg 14 <210> 711 <211> 14 <212> DNA <213> Homo sapiens <400> 711 tctcctcctc ctgc 14 <210> 712 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 712 tctcctcctc ctgc 14 <210> 713 <211> 14 <212> DNA <213> Homo sapiens <400> 713 cccttaaggg cctc 14 <210> 714 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 714 cccttaaggg cctc 14 <210> 715 <211> 14 <212> DNA <213> Homo sapiens <400> 715 aggttcttcc tgtc 14 <210> 716 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 716 aggttcttcc tgtc 14 <210> 717 <211> 14 <212> DNA <213> Homo sapiens <400> 717 gaccttgctc tgca 14 <210> 718 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 718 gaccttgctc tgca 14 <210> 719 <211> 14 <212> DNA <213> Homo sapiens <400> 719 agctcttgac cttg 14 <210> 720 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 720 agctcttgac cttg 14 <210> 721 <211> 14 <212> DNA <213> Homo sapiens <400> 721 gtgctgggcc ttgc 14 <210> 722 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 722 gtgctgggcc ttgc 14 <210> 723 <211> 14 <212> DNA <213> Homo sapiens <400> 723 ttgttggcct gggt 14 <210> 724 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 724 ttgttggcct gggt 14 <210> 725 <211> 14 <212> DNA <213> Homo sapiens <400> 725 cagcttgttg gcct 14 <210> 726 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 726 cagcttgttg gcct 14 <210> 727 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 727 ttgatcttgg cctc 14 <210> 728 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 728 ttgatcttgg cctc 14 <210> 729 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 729 ttgatcttgg cctc 14 <210> 730 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 730 ttgatcttgg cctc 14 <210> 731 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 731 ttgatcttgg cctc 14 <210> 732 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 732 ttgatcttgg cctc 14 <210> 733 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C ethylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C ethylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C ethylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C ethylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C ethylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C ethylene bridged cytidine <400> 733 ttgatcttgg cctc 14 <210> 734 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 734 ttgatcttgg cctc 14 <210> 735 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 735 ttgatcttgg cctc 14 <210> 736 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 736 ttgatcttgg cctc 14 <210> 737 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C ethylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C ethylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C ethylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C ethylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C ethylene bridged cytidine <400> 737 ttgatcttgg cctc 14 <210> 738 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 738 ttgatcttgg cctc 14 <210> 739 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C ethylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 739 ttgatcttgg cctc 14 <210> 740 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 740 ttgatcttgg cctc 14 <210> 741 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C ethylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 741 ttgatcttgg cctc 14 <210> 742 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 742 ttgatcttgg cctc 14 <210> 743 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C ethylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 743 ttgatcttgg cctc 14 <210> 744 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 744 ttgatcttgg cctc 14 <210> 745 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C ethylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 745 ttgatcttgg cctc 14 <210> 746 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 746 ttgatcttgg cctc 14 <210> 747 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C ethylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 747 ttgatcttgg cctc 14 <210> 748 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 748 ttgatcttgg cctc 14 <210> 749 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C ethylene bridged cytidine <400> 749 ttgatcttgg cctc 14 <210> 750 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 750 ttgatcttgg cctc 14 <210> 751 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(3) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (12)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 751 ttgatcttgg cctc 14 <210> 752 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 752 ttgatcttgg cctc 14 <210> 753 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(4) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (11)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 753 ttgatcttgg cctc 14 <210> 754 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 754 ttgatcttgg cctc 14 <210> 755 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(3) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MISC_FEATURE <222> (4)..(5) <223> May be joined through phosphorothioate bonds <220> <221> MISC_FEATURE <222> (6)..(7) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (8)..(9) <223> May be joined through phosphorothioate bonds <220> <221> MISC_FEATURE <222> (10)..(11) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (12)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 755 ttgatcttgg cctc 14 <210> 756 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 756 ttgatcttgg cctc 14 <210> 757 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(2) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MISC_FEATURE <222> (3)..(4) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MISC_FEATURE <222> (5)..(6) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (7)..(8) <223> May be joined through phosphorothioate bonds <220> <221> MISC_FEATURE <222> (9)..(10) <223> May be joined through phosphorothioate bonds <220> <221> MISC_FEATURE <222> (11)..(12) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MISC_FEATURE <222> (13)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 757 ttgatcttgg cctc 14 <210> 758 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 758 ttgatcttgg cctc 14 <210> 759 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(3) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MISC_FEATURE <222> (4)..(7) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (8)..(11) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (12)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 759 ttgatcttgg cctc 14 <210> 760 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 760 ctgcagctcc tcca 14 <210> 761 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl guanosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 761 ctgcagctcc tcca 14 <210> 762 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 762 ctgcagctcc tcca 14 <210> 763 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(3) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MISC_FEATURE <222> (4)..(5) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (6)..(7) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (8)..(9) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (10)..(11) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (12)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 763 ctgcagctcc tcca 14 <210> 764 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 764 ctgcagctcc tcca 14 <210> 765 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(3) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MISC_FEATURE <222> (4)..(7) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (8)..(11) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MISC_FEATURE <222> (12)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 765 ctgcagctcc tcca 14 <210> 766 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 766 ttgatcttgg cctc 14 <210> 767 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 767 tugatcttgg ccuc 14 <210> 768 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <400> 768 ttgatcttgg cctc 14 <210> 769 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime fluoro guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime fluoro cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 769 ttgatcttgg cctc 14 <210> 770 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 770 tcuggatggc auct 14 <210> 771 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl cytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 771 gactgggagc catt 14 <210> 772 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl adenosine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 772 ccaggagcct autc 14 <210> 773 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 773 agacagaagc agca 14 <210> 774 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 774 agutcactca catc 14 <210> 775 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl adenosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl guanosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 775 aaagtgcagg aggg 14 <210> 776 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <400> 776 tcctcagggt cutg 14 <210> 777 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 777 gtucactcac aucc 14 <210> 778 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl cytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (9)..(9) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 778 ttcactcaca tcca 14 <210> 779 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl adenosine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 779 ggutcataga caga 14 <210> 780 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (5)..(5) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 780 atucctcagg guct 14 <210> 781 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl adenosine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (8)..(8) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 781 tcactcacat ccat 14 <210> 782 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <400> 782 agutatcatt cctc 14 <210> 783 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 783 gtuatcattc cuca 14 <210> 784 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O methyl uridine <220> <221> MOD_RES <222> (4)..(4) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O methyl cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <400> 784 acuctcagtg ccat 14 <210> 785 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged thymidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (11)..(11) <223> May be a 2 prime O methyl deoxycytidine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged cytidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged cytidine <400> 785 ttgatcttgg cctc 14 <210> 786 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged cytidine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged guanosine <400> 786 gcaccttgga cttg 14 <210> 787 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(14) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged thymidine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged adenosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime CH2-NH-CH2 4 prime bridged guanosine <400> 787 tgaggttctc cttg 14 <210> 788 <211> 20 <212> PRT <213> Unknown <220> <223> peptide with high selectivity for cardiomyocytes in vivo <400> 788 Trp Leu Ser Glu Ala Gly Pro Val Val Thr Val Arg Ala Leu Arg Gly 1 5 10 15 Thr Gly Ser Trp 20 <210> 789 <211> 15 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(15) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (13)..(13) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (15)..(15) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 789 gtgaatgcgg atgaa 15 <210> 790 <211> 15 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(15) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (2)..(2) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (15)..(15) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 790 gaagtggtag tcata 15 <210> 791 <211> 15 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(15) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (15)..(15) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 791 gtgaatgcgg atgaa 15 <210> 792 <211> 15 <212> DNA <213> Artificial Sequence <220> <223> modified nucleotide MYHB7B antisense oligonucleotide <220> <221> MISC_FEATURE <222> (1)..(15) <223> May be joined through phosphorothioate bonds <220> <221> MOD_RES <222> (1)..(1) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (3)..(3) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <220> <221> MOD_RES <222> (6)..(6) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (7)..(7) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (10)..(10) <223> May be a 2 prime O, 4 prime C methylene bridged guanosine <220> <221> MOD_RES <222> (12)..(12) <223> May be a 2 prime O, 4 prime C methylene bridged cytidine <220> <221> MOD_RES <222> (14)..(14) <223> May be a 2 prime O, 4 prime C methylene bridged thymidine <220> <221> MOD_RES <222> (15)..(15) <223> May be a 2 prime O, 4 prime C methylene bridged adenosine <400> 792 gaagtggtag tcata 15

Claims (41)

  1. MYH7B의 안티센스 올리고뉴클레오티드 억제제로서, 안티센스 올리고뉴클레오티드 억제제는 8 내지 18개 뉴클레오티드의 길이를 가지며, 상기 안티센스 올리고뉴클레오티드의 서열은 SEQ ID NO: 6의 서열에 실질적으로 상보적인 안티센스 올리고뉴클레오티드 억제제.
  2. 제 1 항에 있어서,
    안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4300-4335로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 안티센스 올리고뉴클레오티드 억제제.
  3. 제 2 항에 있어서,
    안티센스 올리고뉴클레오티드는 12 내지 18개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4300-4317로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 안티센스 올리고뉴클레오티드 억제제.
  4. 제 2 항에 있어서,
    안티센스 올리고뉴클레오티드는 12 내지 18개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4316-4333으로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 안티센스 올리고뉴클레오티드 억제제.
  5. 제 3 항에 있어서,
    안티센스 올리고뉴클레오티드는 14개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4302-4315로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 안티센스 올리고뉴클레오티드 억제제.
  6. 제 4 항에 있어서,
    안티센스 올리고뉴클레오티드는 14개 뉴클레오티드의 길이를 가지며, 안티센스 올리고뉴클레오티드의 서열은 뉴클레오티드 4318-4331로부터의 SEQ ID NO: 6의 서열에 실질적으로 상보적인 안티센스 올리고뉴클레오티드 억제제.
  7. 제 1 항에 있어서,
    안티센스 올리고뉴클레오티드는 적어도 하나의 변형 뉴클레오티드를 함유하는 안티센스 올리고뉴클레오티드 억제제.
  8. 제 7 항에 있어서,
    상기 변형 뉴클레오티드는 당, 염기 및/또는 주쇄 변형을 포함하는 안티센스 올리고뉴클레오티드 억제제.
  9. 제 7 항에 있어서,
    상기 변형 뉴클레오티드는 잠금 뉴클레오티드인 안티센스 올리고뉴클레오티드 억제제.
  10. 제 1 항에 있어서,
    상기 안티센스 올리고뉴클레오티드는 1개 내지 6개 잠금 뉴클레오티드를 함유하는 안티센스 올리고뉴클레오티드 억제제.
  11. 제 1 항에 있어서,
    상기 안티센스 올리고뉴클레오티드는 5' 말단에 적어도 3개의 잠금 뉴클레오티드를 함유하는 안티센스 올리고뉴클레오티드 억제제.
  12. 제 1 항에 있어서,
    상기 안티센스 올리고뉴클레오티드는 3' 말단에 적어도 3개의 잠금 뉴클레오티드를 함유하는 안티센스 올리고뉴클레오티드 억제제.
  13. 제 11 항에 있어서,
    5' 말단에 있는 적어도 3개의 잠금 뉴클레오티드는 리보뉴클레오티드인 안티센스 올리고뉴클레오티드 억제제.
  14. 제 12 항에 있어서,
    3' 말단에 있는 적어도 3개의 잠금 뉴클레오티드는 리보뉴클레오티드인 안티센스 올리고뉴클레오티드 억제제.
  15. 제 1 항에 있어서,
    상기 안티센스 올리고뉴클레오티드는 적어도 하나의 데옥시리보뉴클레오티드를 함유하는 안티센스 올리고뉴클레오티드 억제제.
  16. 제 15 항에 있어서,
    상기 안티센스 올리고뉴클레오티드는 2 내지 8개의 데옥시리보뉴클레오티드를 함유하는 안티센스 올리고뉴클레오티드 억제제.
  17. 제 8 항에 있어서,
    당 변형은 2'-O, 4'-C 메틸렌 가교, 2'-O, 4'-C 에틸렌 가교, 2'-CH2-NH-CH2-4' 가교, 2'-데옥시, 2'-O-알킬 및 2'-할로 변형으로 이루어진 그룹으로부터 선택되는 안티센스 올리고뉴클레오티드 억제제.
  18. 제 8 항에 있어서,
    주쇄 변형은 포스포로티오에이트 결합인 안티센스 올리고뉴클레오티드 억제제.
  19. 제 18 항에 있어서,
    상기 안티센스 올리고뉴크레오티드는 둘 이상의 포스포로티오에이트 결합을 함유하는 안티센스 올리고뉴클레오티드 억제제.
  20. 제 19 항에 있어서,
    상기 안티센스 올리고뉴클레오티드는 완전히 포스포로티오에이트 결합되는 안티센스 올리고뉴클레오티드 억제제.
  21. 제 7 항에 있어서,
    상기 변형 뉴클레오티드는 5'-메틸 시티딘인 안티센스 올리고뉴클레오티드 억제제.
  22. 제 1 항에 있어서,
    상기 안티센스 올리고뉴클레오티드는 표 1-5로부터 선택된 서열을 포함하는 안티센스 올리고뉴클레오티드 억제제.
  23. 제 1 항에 있어서,
    상기 안티센스 올리고뉴클레오티드는 5'-lTslTslGsdAsdTsdCsdTsdTsdGsdGsdCslCslTslC-3'(SEQ ID NO: 146) 또는 5'-lCslTslGsdCsdAsdGsdCsdTsdCsdCsdTslCslCslA-3'(SEQ ID NO: 148)의 서열을 포함하는 안티센스 올리고뉴클레오티드 억제제.
  24. 제 1 항 내지 제 23 항 중 어느 한 항의 MYH7B의 안티센스 올리고뉴클레오티드 억제제 및 약학적으로 허용가능한 부형제를 포함하는 약학적 조성물.
  25. 제 24 항에 있어서,
    제 2 치료제를 더 포함하며, 제 2 치료제는 miR-208a, miR-208b, miR-499, miR-15a, miR-15b, miR-16, miR-195 또는 이의 혼합물의 안티센스 올리고뉴클레오티드 억제제인 약학적 조성물.
  26. 제 1 항의 안티센스 올리고뉴클레오티드 억제제를 대상에게 투여하는 단계를 포함하여, 필요한 대상의 병적 심근비대증, 심근경색증 또는 심부전증을 치료 또는 예방하는 방법.
  27. 제 26 항에 있어서,
    병적 심근비대증은 비대성 심근병증인 방법.
  28. 제 26 항에 있어서,
    대상은 병적 심근비대증의 위험이 있는 것인 방법.
  29. 제 28 항에 있어서,
    위험이 있는 대상은 베타 마이오신 중쇄 유전자에서 돌연변이를 갖는 것인 방법.
  30. 제 26 항에 있어서,
    MYH7B의 발현 또는 활성은 억제제의 투여 후 대상의 심장 세포에서 감소되는 것인 방법.
  31. 제 26 항에 있어서,
    베타 마이오신 중쇄의 발현은 억제제의 투여 후 대상의 심장 세포에서 감소되는 것인 방법.
  32. 제 26 항에 있어서,
    대상의 심장 세포에서 miR-499의 발현은 억제제의 투여 후 통계적으로 상이하지 않은 것인 방법.
  33. 제 26 항에 있어서,
    안티센스 올리고뉴클레오티드는 5'-lTslTslGsdAsdTsdCsdTsdTsdGsdGsdCslCslTslC-3'(SEQ ID NO: 146) 또는 5'-lCslTslGsdCsdAsdGsdCsdTsdCsdCsdTslCslCslA-3'(SEQ ID NO: 148)의 서열을 포함하는 것인 방법.
  34. 제 26 항에 있어서,
    제 2 심장 치료제를 투여하는 단계를 더 포함하는 것인 방법.
  35. 제 34 항에 있어서,
    제 2 심장 치료제는 miR-208a, miR-208b, miR-499, miR-15a, miR-15b, miR-16, miR-195 또는 이의 조합의 안티센스 올리고뉴클레오티드 억제제인 방법.
  36. 제 26 항에 있어서,
    대상은 인간인 방법.
  37. MYH7B의 억제제를 대상에게 투여하는 단계를 포함하여, 필요한 대상의 병적 심근비대증, 심근경색증 또는 심부전증을 치료 또는 예방하는 방법.
  38. 제 37 항에 있어서,
    MYH7B의 억제제는 안티센스 올리고뉴클레오티드, 앱타머, 리보자임, 소형 간섭 RNA 또는 소형 헤어핀 RNA로부터 선택되는 핵산 억제제인 방법.
  39. 제 38 항에 있어서,
    핵산 억제제는 약 10 내지 약 30개 뉴클레오티드의 이중 가닥 영역을 포함하는 소형 간섭 RNA 또는 소형 헤어핀 RNA이며, 상기 이중 가닥 영역은 (i) 인간 Myh7b 유전자의 서열과 적어도 70% 동일한 서열을 갖는 제 1 RNA 가닥 및 (ⅱ) 제 1 RNA 가닥에 부분적으로, 실질적으로 또는 완전히 상보적인 제 2 RNA 가닥을 포함하는 것인 방법.
  40. 제 39 항에 있어서,
    제 1 RNA 가닥은 5'-GAGGCCAAGATCAA-3'(SEQ ID NO: 4)의 서열과 적어도 70% 동일한 서열을 갖는 것인 방법.
  41. 제 39 항에 있어서,
    제 1 RNA 가닥은 5'-TGGAGGAGCTGCAG-3'(SEQ ID NO: 5)의 서열과 적어도 70% 동일한 서열을 갖는 것인 방법.
KR1020177005777A 2014-08-04 2015-08-04 Myh7b의 억제제 및 이의 용도 KR20170042625A (ko)

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Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9752144B2 (en) 2014-08-04 2017-09-05 MiRagen Therapeutics, Inc. Inhibitors of MYH7B and uses thereof
AU2015304945B2 (en) * 2014-08-20 2022-04-07 Lifesplice Pharma Llc Splice modulating oligonucleotides and methods of use thereof
US11015196B2 (en) 2016-05-20 2021-05-25 The General Hospital Corporation Using microRNAs to control activation status of hepatic stellate cells and to prevent fibrosis in progressive liver diseases
AU2017368050A1 (en) 2016-11-29 2019-06-20 Puretech Lyt, Inc. Exosomes for delivery of therapeutic agents
EP3813844A1 (en) * 2018-06-28 2021-05-05 United Kingdom Research and Innovation Treatment of cardiomyopathy through modulation of hypoxia-induced erna activity
WO2020028842A1 (en) * 2018-08-02 2020-02-06 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating hypertrophic cardiomyopathy
KR20210081324A (ko) 2018-08-02 2021-07-01 다인 세라퓨틱스, 인크. 근육 표적화 복합체 및 안면견갑상완 근육 이영양증을 치료하기 위한 그의 용도
US11638761B2 (en) 2021-07-09 2023-05-02 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating Facioscapulohumeral muscular dystrophy

Family Cites Families (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5270163A (en) 1990-06-11 1993-12-14 University Research Corporation Methods for identifying nucleic acid ligands
US7517644B1 (en) * 1991-08-23 2009-04-14 Larry J. Smith Method and compositions for cellular reprogramming
US5981505A (en) 1993-01-26 1999-11-09 The Trustees Of The University Of Pennsylvania Compositions and methods for delivery of genetic material
AU7404994A (en) 1993-07-30 1995-02-28 Regents Of The University Of California, The Endocardial infusion catheter
US5837533A (en) 1994-09-28 1998-11-17 American Home Products Corporation Complexes comprising a nucleic acid bound to a cationic polyamine having an endosome disruption agent
US5840710A (en) 1994-12-09 1998-11-24 Genzyme Corporation Cationic amphiphiles containing ester or ether-linked lipophilic groups for intracellular delivery of therapeutic molecules
US6639062B2 (en) * 1997-02-14 2003-10-28 Isis Pharmaceuticals, Inc. Aminooxy-modified nucleosidic compounds and oligomeric compounds prepared therefrom
US6416510B1 (en) 1997-03-13 2002-07-09 Biocardia, Inc. Drug delivery catheters that attach to tissue and methods for their use
US6217900B1 (en) 1997-04-30 2001-04-17 American Home Products Corporation Vesicular complexes and methods of making and using the same
WO1999001579A1 (en) 1997-07-01 1999-01-14 Isis Pharmaceuticals, Inc. Compositions and methods for the delivery of oligonucleotides via the alimentary canal
US6749617B1 (en) 1997-11-04 2004-06-15 Scimed Life Systems, Inc. Catheter and implants for the delivery of therapeutic agents to tissues
NZ507913A (en) 1998-05-26 2003-02-28 Icn Pharmaceuticals Novel nucleosides having bicyclic sugar moiety
US6838283B2 (en) 1998-09-29 2005-01-04 Isis Pharmaceuticals Inc. Antisense modulation of survivin expression
US6716242B1 (en) 1999-10-13 2004-04-06 Peter A. Altman Pulmonary vein stent and method for use
US6693187B1 (en) 2000-10-17 2004-02-17 Lievre Cornu Llc Phosphinoamidite carboxlates and analogs thereof in the synthesis of oligonucleotides having reduced internucleotide charge
US7083642B2 (en) 2000-12-22 2006-08-01 Avantec Vascular Corporation Delivery of therapeutic capable agents
US7247313B2 (en) 2001-06-27 2007-07-24 Advanced Cardiovascular Systems, Inc. Polyacrylates coatings for implantable medical devices
US6589286B1 (en) 2001-09-12 2003-07-08 Jason Litner Eustachian tube stent
US7236821B2 (en) 2002-02-19 2007-06-26 Cardiac Pacemakers, Inc. Chronically-implanted device for sensing and therapy
AU2003266014B2 (en) 2002-05-06 2009-05-14 Alnylam Pharmaceuticals, Inc. Methods for delivery of nucleic acids
US20040133270A1 (en) 2002-07-08 2004-07-08 Axel Grandt Drug eluting stent and methods of manufacture
US7294329B1 (en) 2002-07-18 2007-11-13 Advanced Cardiovascular Systems, Inc. Poly(vinyl acetal) coatings for implantable medical devices
US7232573B1 (en) 2002-09-26 2007-06-19 Advanced Cardiovascular Systems, Inc. Stent coatings containing self-assembled monolayers
US7087263B2 (en) 2002-10-09 2006-08-08 Advanced Cardiovascular Systems, Inc. Rare limiting barriers for implantable medical devices
US7144422B1 (en) 2002-11-13 2006-12-05 Advanced Cardiovascular Systems, Inc. Drug-eluting stent and methods of making the same
JP2006507841A (ja) 2002-11-14 2006-03-09 ダーマコン， インコーポレイテッド 機能的ｓｉＲＮＡおよび超機能的ｓｉＲＮＡ
US7105018B1 (en) 2002-12-30 2006-09-12 Advanced Cardiovascular Systems, Inc. Drug-eluting stent cover and method of use
US7156869B1 (en) 2003-01-27 2007-01-02 Advanced Cardiovascular Systems, Inc. Drug-eluting stent and delivery system with tapered stent in shoulder region
US7041127B2 (en) 2003-05-28 2006-05-09 Ledergerber Walter J Textured and drug eluting coronary artery stent
US7055237B2 (en) 2003-09-29 2006-06-06 Medtronic Vascular, Inc. Method of forming a drug eluting stent
US20070203445A1 (en) 2004-02-26 2007-08-30 V-Kardia Pty Ltd Isolating cardiac circulation
EP1735037B1 (en) 2004-02-26 2015-05-20 Osprey Medical Inc. Isolating cardiac circulation
US7722596B2 (en) 2004-02-26 2010-05-25 Osprey Medical, Inc. Regional cardiac tissue treatment
US7842800B2 (en) * 2004-04-02 2010-11-30 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory bacterial and bacterial associated oligonucleotides and uses thereof
WO2006089340A2 (en) 2005-02-23 2006-08-31 V-Kardia Pty Ltd Polynucleotide delivery to cardiac tissue
CA2622584C (en) 2005-09-15 2015-08-11 Novosom Ag Improvements in or relating to amphoteric liposomes
US8367627B2 (en) 2005-09-15 2013-02-05 Duke University Focused libraries, functional profiling, laser SELEX, and DESELEX
WO2008076324A2 (en) * 2006-12-14 2008-06-26 Novartis Ag Compositions and methods to treat muscular & cardiovascular disorders
MX2010001216A (es) * 2007-07-31 2010-04-30 Univ Texas Microarn que controla la expresion de miosina y la identidad de miofibras.
AU2008306327B2 (en) * 2007-10-04 2014-05-15 Roche Innovation Center Copenhagen A/S Micromirs
US8629119B2 (en) * 2009-02-04 2014-01-14 The Board Of Regents, The University Of Texas System Dual targeting of MIR-208 and MIR-499 in the treatment of cardiac disorders
EP3165606A1 (en) * 2009-05-01 2017-05-10 Ophthotech Corporation Methods for treating or preventing ophthalmological diseases
EP2611918A1 (en) * 2010-05-28 2013-07-10 Vereniging Voor Christelijk Hoger Onderwijs, Weten Mirnas involved in the blood brain barrier function
AU2011343720A1 (en) * 2010-12-15 2013-04-11 Miragen Therapeutics MicroRNA inhibitors comprising locked nucleotides
WO2012140234A1 (en) * 2011-04-13 2012-10-18 Vib Vzw Modulation of mirna in diseases with aberrant angiogenesis
EP3401401B1 (en) * 2011-09-20 2020-04-15 Ionis Pharmaceuticals, Inc. Antisense modulation of gcgr expression
EP2763703B1 (en) * 2011-10-06 2018-02-14 Miragen Therapeutics, Inc. Control of whole body energy homeostasis by microrna regulation
CN104704122A (zh) * 2012-04-20 2015-06-10 艾珀特玛治疗公司 产热的miRNA调节剂
US9034839B2 (en) 2012-04-20 2015-05-19 Aptamir Therapeutics, Inc. miRNA modulators of thermogenesis
CN104602714A (zh) * 2012-05-16 2015-05-06 Rana医疗有限公司 用于调节bdnf表达的组合物和方法
US9163235B2 (en) 2012-06-21 2015-10-20 MiRagen Therapeutics, Inc. Inhibitors of the miR-15 family of micro-RNAs
CA2876180C (en) * 2012-06-21 2019-11-19 MiRagen Therapeutics, Inc. Oligonucleotide-based inhibitors comprising locked nucleic acid motif
US9752144B2 (en) 2014-08-04 2017-09-05 MiRagen Therapeutics, Inc. Inhibitors of MYH7B and uses thereof

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AR101449A1 (es) 2016-12-21
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WO2016022536A3 (en) 2016-03-31
CN108064175A (zh) 2018-05-22
AU2015301221A1 (en) 2017-03-02
TW201614069A (en) 2016-04-16
WO2016022536A2 (en) 2016-02-11
US9752144B2 (en) 2017-09-05
AU2015301221B2 (en) 2020-07-02
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