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US 2013/0174286 A1Published application
In Vivo Gene Silencing By Chemically Modified and Stable siRNA
AssigneeUniversity of Massachusetts
InventorTariq M. Rana
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AssigneeUniversity of Massachusetts
InventorTariq M. Rana
Estimating the term…
The present invention provides compositions for RNA interference and methods of use thereof. In particular, the invention provides small interfering RNAs (siRNAs) having modification that enhance the stability of the siRNA without a concomitant loss in the ability of the siRNA to participate in RNA interference (RNAi). The invention also provides siRNAs having modification that increase targeting efficiency. Modifications include chemical crosslinking between the two complementary strands of an siRNA and chemical modification of a 3′ terminus of a strand of an siRNA. Preferred modifications are internal modifications, for example, sugar modification, nucleobase modification and/or backbone modifications. Such modifications are also useful, e.g., to improve uptake of the siRNA by a cell. Functional and genomic and proteomic methods are featured. Therapeutic methods are also featured.
A small interfering RNA (siRNA), comprising a sense strand and an antisense strand, wherein the antisense strand has a sequence sufficiently complementary to a target mRNA sequence to direct target-specific RNA interference (RNAi) and wherein the sense strand or antisense strand is modified by the substitution of at least one internal nucleotide with a modified nucleotide, such that in vivo stability is enhanced as compared to a corresponding unmodified siRNA or such that the target efficiency is enhanced compared to a corresponding unmodified siRNA.
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An siRNA derivative comprising an siRNA having two complementary strands of nucleic acid, wherein the two strands are crosslinked, a 3′ OH terminus of one of the strands is modified, or the two strands are crosslinked and modified at the 3′OH terminus, wherein the siRNA derivative
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A small interfering RNA (siRNA), comprising a sense strand and an antisense strand, wherein the antisense strand is complementary to the sense strand and has a sequence sufficiently complementary to a Spt5 target mRNA sequence to direct target-specific RNA interference (RNAi).
A small interfering RNA (siRNA), comprising a sense strand and an antisense strand, wherein the antisense strand is complementary to the sense strand and has a sequence sufficiently complementary to a CDK9 target mRNA sequence to direct target-specific RNA interference (RNAi).
A small interfering RNA (siRNA), comprising a sense strand and an antisense strand, wherein the antisense strand is complementary to the sense strand and has a sequence sufficiently complementary to a hCycT1 target mRNA sequence to direct target-specific RNA interference (RNAi).
Dependencies are inferred from the claim text.