Patent ID: 8765930

Claim:
A method of stabilizing a synthetic, double-stranded RNA interference (RNAi) agent, comprised of two separate RNA strands, against RNAse mediated degradation, said method comprising substituting at least one ribonucleotide in the RNAi agent with a sugar-modified ribonucleotide, wherein the 2′-OH group of said sugar-modified ribonucleotide is replaced by a group selected from the group consisting of H, OR, R, halo, SH, SR, NH 2 , NHR, NR 2 and CN, wherein R is C 1 -C 6 alkyl, C 2 -C 6 alkenyl or alkynyl and halo is F, Cl, Br or I; and/or substituting at least one ribonucleotide in the RNAi agent with a backbone-modified ribonucleotide containing a phosphorothioate group; and wherein: (i) each RNA strand in said RNAi agent independently consists of 19-25 nucleotides, (ii) at least one strand of said RNAi agent has a single-stranded 3′-overhang from 1-5 nucleotides and said 3′-overhang comprises one or more nucleotide analogues, and (iii) the resultant stabilized RNAi agent is capable of sequence specific mRNA degradation.