Conserved HBV and HCV sequences useful for gene silencing
View Patent ↗Conserved consensus sequences from known hepatitis B virus strains and known hepatitis C virus strains, which are useful in inhibiting the expression of the viruses in mammalian cells, are provided. These sequences are useful to silence the genes of HBV and HCV, thereby providing therapeutic utility against HBV and HCV viral infection in humans.
1. A method for inhibiting expression of a polynucleotide sequence of hepatitis B virus in an in vivo mammalian cell comprising administering to said cell a double-stranded RNA effector molecule said double-stranded RNA effector molecule: (1) comprising: (a) a sequence selected from the group consisting of SEQ ID NO:57, SEQ ID NO: 56, and SEQ ID NO: 60; (b) the reverse complement of said selected sequence; wherein U is substituted for T; or (2) consisting of: (a) a sequence selected from SEQ ID NO: 54 or SEQ ID NO: 55, and (b) the reverse complement of said selected sequence; wherein U is substituted for T.
2. The method of claim 1 , wherein said at double-stranded RNA effector molecule is administered to the cell by providing at least one expression vector encoding the double-stranded RNA effector molecule.
3. The method of claim 1 , wherein the double-stranded RNA effector molecule is a hairpin dsRNA molecule.
4. The method of claim 2 , wherein the expression vector comprises at least one promoter selected from the group consisting of a polymerase I promoter, a polymerase III promoter, a U6 promoter, an H1 promoter, a 7SK promoter, and a mitochondrial promoter, said promoter operably linked to a sequence encoding one or more of said double-stranded RNA effector molecules.
5. A composition for inhibiting expression of a polynucleotide sequence of hepatitis B virus in an in vivo mammalian cell comprising a double-stranded RNA effector molecule said double-stranded RNA effector molecule: (1) comprising: (a) a sequence selected from the group consisting of SEQ ID NO:57, SEQ ID NO: 56, and SEQ ID NO: 60; and (b) the reverse complement of said selected sequence; wherein U is substituted for T; or (2) consisting of: (a) a sequence selected from SEQ ID NO: 54 or SEQ ID NO: 55, and (b) the reverse complement of said selected sequence; wherein U is substituted for T.
6. The composition of claim 5 , comprising at least one expression vector encoding said double-stranded RNA effector molecules.
7. The composition of claim 5 , wherein the double-stranded RNA effector molecule is a hairpin dsRNA molecule.
8. The composition of claim 6 , wherein the expression vector comprises at least one promoter selected from the group consisting of a polymerase I promoter, a polymerase III promoter, a U6 promoter, an H1 promoter, a 7SK promoter, and a mitochondrial promoter, said promoter operably linked to a sequence encoding one or more of said double-stranded RNA effector molecules.
9. The method of claim 1 , further comprising a sequence linking sequences (a) and (b).
10. The method of claim 1 , wherein said double-stranded RNA effector molecule comprises: (a) a sequence selected from the group consisting of SEQ ID NO:57, SEQ ID NO: 56, and SEQ ID NO: 60; and (b) the reverse complement of said selected sequence.
11. The composition of claim 5 , further comprising a sequence linking sequences (a) and (b).
12. The composition of claim 5 , wherein said double-stranded RNA effector molecule comprises: (a) a sequence selected from the group consisting of SEQ ID NO:57, SEQ ID NO: 56, and SEQ ID NO: 60; and (b) the reverse complement of said selected sequence.