MODIFIED SMALL INTERFERING RNA MOLECULES AND METHODS OF USE

摘要

The present invention provides double-stranded RNA molecules that mediate RNA interference in target cells, preferably hepatic cells. The invention also provides double-stranded RNA (dsRNA) molecules that are modified to be resistant to nuclease degradation, which inactivates a virus, and more specifically, hepatitis C virus (HCV). The invention also provides a method of using these modified RNA molecules to inactivate virus in mammalian cells and a method of making modified small interfering RNAs (siRNAs) using human Dicer. The invention provides modified RNA molecules that are modified to include a dsRNA or siRNA wherein one or more of the pyrimidines in the RNA molecule are modified to include 2′-Fluorine. The invention also provides dsRNA or siRNA in which all pyrimidines are modified to include a 2′-Fluorine. The invention provides that the 2′-Fluorine dsRNA or siRNA molecule is further modified to include a two base deoxynucleotide “TT” sequence at the 3′ end of the molecule.

主权项

1. A method for inactivating Hepatitis C Virus (HCV) in a patient, the method comprising the step of administering to said patient a siRNA in an amount effective to inactivate said virus, wherein said siRNA comprises a first strand and a second strand, wherein the sequence of said first strand is SEQ ID NO: 46 and the sequence of said second strand is selected from the group of SEQ ID NO: 18 and SEQ ID NO: 45.