Martin Maier,Don Foster,Stuart Milstein,Satya Kuchimanchi,Vasant Jadhav,Kallanthottathil Rajeev,Muthiah Manoharan,Rubina Parmar
申请号：
US16272721
公开号：
US10612024B2
申请日:
2019.02.11
申请国别(地区):
US
年份:
2020
代理人:
摘要：
One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand； and the antisense strand of the dsRNA agent comprises at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2′；-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.
