ANTONIN DE FOUGEROLLES,ERIC YI-CHUN HUANG,JEFF LYNN ELLSWORTH,JOSEPH BEENE BOLEN,JUSTIN GUILD,STEPHEN G. HOGE
申请号：
BR112015023386
公开号：
BR112015023386A8
申请日:
2014.03.14
申请国别(地区):
BR
年份:
2018
代理人:
摘要：
A composition, characterized in that it comprises: (a) synthetic polynucleotide encoding negative ldlr pcsk9, and (b) synthetic polynucleotide encoding cyp7a1 in an acceptable diluent or carrier. Composition according to Claim 1, characterized in that it further comprises: (c) a statin selected from the group consisting of atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, simvastatin, and combinations thereof. Composition according to Claim 1 or 2, characterized in that the synthetic polynucleotide comprises: (a) first region of linked nucleosides, said first region encoding at least one cholesterol regulating polypeptide； (b) first flanking region located at the 5 'terminus of said first region comprising: (i) linked nucleoside sequence selected from the group consisting of 5' native untranslated region (utr), seq id no: 1 and variants functional factors； (c) second flanking region located at the 3 'terminus of said first region comprising:； (i ') linked nucleoside sequence selected from the group consisting of a native 3', any of the foregoing comprising one or more microrna or microrna binding site or seeds and functional variants or combinations thereof； and (ii ') 3' tail sequence of linked nucleosides； wherein the first bound nucleoside region comprises at least one modified first nucleoside. Composition according to Claim 3, characterized in that the second flanking region encodes at least one mir binding site. Composition according to Claim 4, characterized in that said mir binding site is selected from the group consisting of mir-122a and mir-422a. Composition according to any one of Claims 1 to 5, characterized in that the synthetic polynucleotide comprises at least one chemical modification. A method according to which it comprises contacting a hepatocyte in an individual with the composition as defined in any one of claims 1 to 6. A method according to claim 7, further comprising measuring cholesterol levels. in
