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OLIGONUCLEOTIDES COMPRISING A MODIFIED OR NON-NATURAL NUCLEOBASE
专利权人:
ALNYLAM PHARMACEUTICALS; INC.
发明人:
MANOHARAN, MUTHIAH,XIA, JIE,RAJEEV, KALLANTHOTTATHIL G.
申请号:
CA2574088
公开号:
CA2574088C
申请日:
2005.07.21
申请国别(地区):
CA
年份:
2013
代理人:
摘要:
One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain e4mbodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphrothioate linkage.
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