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.