Back to results
US 9,284,551 B2Granted
RNAi sequence-independent modification formats, and stabilized forms thereof
AssigneeApplied Biosystems, LLC
InventorsNitin Puri, Irudaya Charles, Susan Magdaleno, Alexander Vlassov, Chris Burnett
Life of this patent
Estimating the term…
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.
Claims7
A RNA, comprising:
- a sense oligonucleotide having a length of 17 to 30 nucleotides and comprising:
- sequence-independent modification:
- 5′ mp-Nx-m-m-Nq-nr 3′ wherein p is 2, x is 10;
- r is 0, 1, or 2;
- and q is an integer representing the length of the sense oligonucleotide minus (p+x+r+2);
- and
- an antisense oligonucleotide having 17 to 30 nucleotides, a region of continuous complementarity to the sense oligonucleotide of at least 12 nucleotides;
- the antisense oligonucleotide further having complementarity to at least a portion of a target mRNA;
- wherein
- each m is independently a 2′-modified nucleotide wherein the 2′ modification is OR
- wherein R is alkyl, and where the alkyl portion is C1-C6;
- each n is independently a deoxynucleotide, modified nucleotide, or ribonucleotide;
- and
- each N is independently a nucleotide other than the 2′-modified nucleotide,
- wherein the RNA does not have Format G:
- Passenger (Sense) Strand Guide (Antisense) Strand
13 more elements
Dependencies are inferred from the claim text.