METHODS AND COMPOSITIONS FOR THE SPECIFIC INHIBITION OF GENE EXPRESSION BY DOUBLE-STRANDED RNA

摘要

The invention is directed to compositions and methods for selectively reducing the expression of a gene product from a desired target gene in a cell, as well as for treating diseases caused by the expression of the gene. More particularly, the invention is directed to compositions that contain double stranded RNA (“dsRNA”), and methods for preparing them, that are capable of reducing the expression of target genes in eukaryotic cells. The dsRNA has a first oligonucleotide sequence that is between 25 and about 30 nucleotides in length and a second oligonucleotide sequence that anneals to the first sequence under biological conditions. In addition, a region of one of the sequences of the dsRNA having a sequence length of at least 19 nucleotides is sufficiently complementary to a nucleotide sequence of the RNA produced from the target gene to trigger the destruction of the target RNA by the RNAi machinery.

主权项

1. A nucleic acid molecule capable of reducing expression of a target gene comprising:
a first oligonucleotide strand 25-30 nucleotides in length comprising RNA, a 3′ terminus and a 5′ terminus, and a second oligonucleotide strand at least 26 nucleotides in length comprising RNA, a 3′ terminus, and a 5′ terminus, wherein said second strand is annealed to said first strand under biological conditions to form a duplex region of at least 25 nucleotides in length, wherein the 5′ terminus of said second strand and the 3′ terminus of said first strand form a blunt end, wherein the 3′ terminus of said second strand comprises 1-4 single-stranded nucleotides, wherein said second oligonucleotide strand is sufficiently complementary to a target mRNA encoded by said target gene to reduce expression of said target gene when said nucleic acid molecule is introduced to a mammalian cell; andwherein said nucleic acid molecule reduces expression of said target gene.