Extended dicer substrate agents and methods for the specific inhibition of gene expression

An isolated double stranded nucleic acid comprising:

• a first oligonucleotide strand having a 5′ terminus and a 3′ terminus and a second oligonucleotide strand having a 5′ terminus and a 3′ terminus, wherein each said 5′ terminus comprises a 5′ terminal nucleotide and each said 3′ terminus comprises a 3′ terminal nucleotide;
• and
• an extended loop at the 3′ terminus of said first strand or the 5′ terminus of said second strand;
• wherein said first strand is 35-60 nucleotide residues in length;
• wherein said second strand is 19-39 nucleotide residues in length;
• wherein from 1-30 consecutive nucleotides, including the 5′ terminal nucleotide, of said first strand are unpaired with the 3′ terminus of said second strand, thereby forming a 1-30 nucleotide single stranded 5′ overhang on said first strand;
• wherein said first strand is annealed to said second strand to form a duplex region of 18-30 base pairs;
• and
• wherein said second strand is sufficiently complementary to a target RNA along at least 19 ribonucleotides of said second strand length to reduce target gene expression when said double stranded nucleic acid is introduced into a mammalian cell.