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US 10,329,564 B2Granted
siRNA sequence-independent modification formats for reducing off-target phenotypic effects in RNAi, and stabilized forms thereof
AssigneeApplied Biosystems, LLC
InventorsNitin Puri, Irudaya Charles, Susan Maylin Magdaleno, Alexander Vlassov, Christopher Burnett
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Abstract
Modification formats having modified nucleotides are provided for siRNA. Short interfering RNA having modification formats and modified nucleotides provided herein reduce off-target effects in RNA interference of endogenous genes. Further modification formatted siRNAs are demonstrated to be stabilized to nuclease-rich environments. Unexpectedly, increasing or maintaining strand bias, while necessary to maintain potency for endogenous RNA interference, is not sufficient for reducing off-target effects in cell biology assays.
Claims18
A RNA, comprising:
- a passenger oligonucleotide having a length of 15 to 30 nucleotides and consisting of a modification format wherein nucleotides 1, 2, 13, and 14 are modified wherein nucleotides are numbered from the 5′ end, and
- a guide oligonucleotide having a length of 15 to 30 nucleotides, a region of continuous complementarity to the passenger oligonucleotide of at least 12 nucleotides, and complementarity to at least a portion of target noncoding RNA,
- wherein each modified nucleotide is independently a bicyclonucleotide, a tricyclonucleotide, or a 2′-modified nucleotide.
Dependencies are inferred from the claim text.