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 formulation comprising a nucleic acid molecule capable of reducing the expression of a target gene, the nucleic acid molecule comprising:
a first oligonucleotide strand that is 25-30 nucleotides in length and contains 1-3 DNA bases on the 3′ end of the first oligonucleotide strand; and a second oligonucleotide strand that is 25-30 nucleotides in length comprising an overhang of unmodified and/or modified nucleotides and a domain that hybridizes to the first oligonucleotide strand comprising unmodified and modified nucleotides, wherein said second oligonucleotide strand is sufficiently complementary to a target mRNA encoded by said target gene to reduce target gene expression when said nucleic acid molecule is introduced into a subject or a cell derived from said subject.