Methods and compositions for the specific inhibition of gene expression by double-stranded RNA

A double stranded nucleic acid molecule comprising first and second oligonucleotide strands, each strand comprising RNA and having a 5′ terminus and a 3′ terminus, wherein starting from the first nucleotide (position 1) at the 3′ terminus of the first oligonucleotide strand, position 1, 2 and/or 3 is substituted with a modified nucleotide, wherein said first strand has a length which is at least 25 and at most 30 nucleotides and wherein said second strand is at least one and at most four nucleotides longer at its 3′ terminus than said first strand and forms a blunt end at its 5′ terminus with said 3′ terminus of said first strand, wherein said double-stranded nucleic acid comprises a duplex region of at least 25 nucleotides in length, and wherein said second oligonucleotide strand comprises a sequence complementary to a target mRNA of a target gene and said double stranded nucleic acid molecule reduces target gene expression when introduced into a mammalian cell.

A double stranded nucleic acid molecule comprising first and second oligonucleotide strands, each strand comprising RNA and having a 5′ terminus and a 3′ terminus, wherein starting from the first nucleotide (position 1) at the 3′ terminus of the first oligonucleotide strand, position 1, 2 and/or 3 is substituted with a modified nucleotide, wherein said first strand has a length which is at least 25 and at most 29 nucleotides and said second strand has a length which is at most 30 nucleotides, wherein said 3′ terminus of said first strand and said 5′ terminus of said second strand form a blunt end and said second strand is at least one and at most four nucleotides longer at its 3′ terminus than said first strand, wherein said double-stranded nucleic acid comprises a duplex region of at least 25 nucleotides in length, and wherein said second oligonucleotide strand comprises a sequence complementary to a target mRNA of a target gene and said double stranded nucleic acid molecule reduces target gene expression when introduced into a mammalian cell.

A double stranded nucleic acid molecule comprising first and second oligonucleotide strands, each strand comprising RNA and having a 5′ terminus and a 3′ terminus, wherein said first strand is 25 nucleotide residues in length, and wherein starting from the first nucleotide (position 1) at the 3′ terminus of the first oligonucleotide strand, position 1, 2 and/or 3 is substituted with a modified nucleotide, and said second oligonucleotide strand is 27 nucleotide residues in length and is two nucleotides longer at its 3′ terminus than said first strand, wherein said double-stranded nucleic acid molecule comprises a duplex region of at least 25 nucleotides in length, wherein said second strand comprises a sequence complementary to a target mRNA of a target gene and forms a base-paired blunt end at its 5′ terminus with said 3′ terminus of said first strand, wherein said double stranded nucleic acid molecule reduces target gene expression when introduced into a mammalian cell.