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 pharmaceutical composition comprising an isolated double stranded nucleic acid and a pharmaceutically acceptable carrier, wherein the double stranded nucleic acid comprises first and second oligonucleotide strands, each strand comprising ribonucleotides, having a 5′ terminus and a 3′ terminus and having a length which is at least 25 and at most 30 nucleotides, wherein said second strand comprises a sequence complementary to a target mRNA of a target gene, wherein said double-stranded nucleic acid comprises a duplex region of at least 25 nucleotides in length, wherein said double stranded nucleic acid is present in said pharmaceutical composition in an amount effective to reduce target gene expression when said pharmaceutical composition is administered to a mammal.