Synthetic double-stranded oligonucleotides for specific inhibition of gene expression

A double-stranded RNA oligonucleotide of Formula I

• 5′-(U)vX-(N)x-(W)-3′
• 3′-(Z)n-(N′)y-5′ Formula I
• wherein
• N and N′ are naturally occurring nucleotides bound by 3′,5′ internucleotide bonds, wherein a portion of the oligonucleotide is double-stranded between (N)x and (N′)y, and wherein the nucleotide strand (N)x, is sufficiently complementary to a target RNA to hybridize thereto and inhibit its expression through RNA interference, and wherein the nucleotide strand (N′)y is at least partially homologous to the target RNA, and wherein
• N is selected from the group consisting of adenine (A), cytosine (C), guanine (G), and uracil (U);
• x is independently 15-25;
• y is independently 15-25;
• n is independently 4 to 6;
• v is independently 1 to 20, whereas:
• when v=1, X is selected from the group consisting of A, C, and G, and when v=2 to 20, X is absent;
• W is selected from the group consisting of U2-20, UA, UC, and UG, or is absent;
• and Z is A;
• nucleotides of W being linked via a 3′,5′ internucleotide bond, and
• wherein at least two nucleotides of Z are linked via a 2′,5′ internucleotide bond and are present in a single-stranded form that does not base pair with the target gene or with the RNA homologous thereto, thereby forming a 2′,5′ linked oligonucleotide residue on the 3′ end of the nucleotide strand (N′)y and wherein the internucleotide bonds in the double-stranded oligonucleotide are 3′,5′ or 2′,5′ internucleotide bonds.