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NOVEL FORMATS FOR ORGANIC COMPOUNDS FOR USE IN RNA INTERFERENCE
专利权人:
NOVARTIS AG
发明人:
HUNZIKER, Juerg,NATT, Francois Jean-Charles,PATNAIK, Anup,PATTERSON, Andrew,RONDEAU, Jean-Michel Rene,WEILER, Jan,ZHU, Meicheng,BARYZA, Jeremy Lee,BLOMMERS, Marcel,CHUTKOW, William,FERNANDEZ, Cesar,GE
申请号:
USUS2014/059301
公开号:
WO2015/051366A2
申请日:
2014.10.06
申请国别(地区):
WO
年份:
2015
代理人:
摘要:
The disclosure relates to compositions comprising a RNAi agent having a novel format including a spacer subunit. The disclosure relates to compositions comprising a RNAi agent having a novel format: an 18-mer format with at least one internal spacer. These RNAi agents comprise a first and a second 18-mer strand, wherein the first strand is 18 ribonucleotides or 18 total ribonucleotides and spacer subunit(s), and the second strand is 18 total ribonucleotides and spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer a spacer subunit can be at any position in the strand the two strands form a duplex with at least one blunt end and the 3 end of one or both strands terminates in a phosphate or modified internucleoside linker and further comprises, in 5 to 3 order: a second spacer a second phosphate or modified internucleoside linker, and a 3 end cap. In various embodiments, the RNAi agents comprise a first and a second strand, wherein each strand is a 30-mer or shorter, the first strand comprises ribonucleotides, and the second strand comprises ribonucleotides and one or more spacer subunit(s), wherein: each spacer subunit consists of: (a) a phosphate or modified internucleoside linker and (b) a spacer a spacer subunit can be at any position in the strand. In some embodiments, the 3 end of both strands further comprise, in 5 to 3 order: a second spacer a second phosphate or modified internucleoside linker and a 3 end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3 end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the first two base-pairing nucleotides on the 3 end of the one or both strand are 2-MOE. Optionally, the RNAi agent can be modified on one or both 5 end. Optiona
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