Patent ID: 9012623
Filing Date: 2015-04-21
Classification: A01K,A61K,C07D,C12N,C12Y

Abstract:
1. 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 target mRNA sequence to direct target-specific RNA interference (RNAi), and wherein the target mRNA sequence comprises a cleavage site for RISC, and wherein the sense strand and the antisense strand comprise uridines, cytidines, adenosines and guanosines with at least one adenosine or guanosine within 2 nucleotides upstream and 9 nucleotides downstream of the cleavage site referencing the antisense strand and at least one adenosine or guanosine that is not within 2 nucleotides upstream and 9 nucleotides downstream of the cleavage site referencing the antisense strand, and wherein the sense strand and the antisense strand are modified by the substitution of each uridine with a 2′-fluoro uridine and each cytidine with a 2′-fluoro cytidine, and wherein the adeno sines and guano sines of the sense strand are 2′-ribonucleotides, and wherein the antisense strand is modified by the substitution of at least one adenosine with 2′-deoxy adenosine or at least one guanosine with 2′-deoxy guanosine within 2 nucleotides upstream and 9 nucleotides downstream of the cleavage site, and wherein the adenosine and guano sine nucleotides of the antisense strand that are not within 2 nucleotides upstream and 9 nucleotides downstream of the cleavage site are unmodified, 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.