EGS-mediated inactivation of target RNA
AssigneeInnovir Laboratories, Inc.
InventorsShaji T. George, Michael Ma, Martina Werner, Umberto Pace, Allan R. Goldberg
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Abstract
Modified external guide sequence (EGS) molecules that mediate cleavage of specific target RNAs have been constructed. The modified molecules are external guide sequence molecules for RNAse P which are designed to specifically bind to and promote RNAse P-mediated cleavage of target RNA molecules and to have enhanced nuclease resistance. Specific regions are modified to achieve enhanced stability while maintaining RNAse P activity. Modified external guide sequence molecules suitable for use in the treatment of hepatitis B viral infections have been constructed.
Claims29
An external guide sequence comprising an isolated oligonucleotide molecule comprising
- a RNAse P cleavage targeting sequence, and
- a recognition sequence complementary to a targeted sequence in a target RNA molecule,
- wherein the external guide sequence promotes RNAse P-mediated cleavage of the target RNA molecule, and
- wherein at least one nucleotide in the external guide sequence is selected from the group consisting of modified nucleotides and unmodified deoxyribonucleotides.
An external guide sequence comprising a nucleotide base sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 5, and SEQ ID NO. 6.
An external guide sequence comprising an isolated oligonucleotide molecule comprising
- a RNAse P cleavage targeting sequence, and
- a recognition sequence complementary to a targeted sequence in a hepatitis B RNA molecule,
- wherein the external guide sequence promotes RNAse P-mediated cleavage of the hepatitis B RNA molecule.
A method for cleaving a target RNA molecule comprising
- bringing into contact, under conditions that promote RNAse P cleavage, RNAse P, the target RNA molecule, and an external guide sequence which comprises an isolated oligonucleotide molecule comprising
- a RNAse P cleavage targeting sequence, and
- a recognition sequence complementary to a targeted sequence in a target RNA molecule,
- wherein the external guide sequence promotes RNAse P-mediated cleavage of the target RNA molecule, and
- wherein at least one nucleotide in the external guide sequence is selected from the group consisting of modified nucleotides and unmodified deoxyribonucleotides.
An engineered expression vector encoding an external guide sequence comprising an isolated oligonucleotide molecule comprising
- a RNAse P cleavage targeting sequence, and
- a recognition sequence complementary to a targeted sequence in a hepatitis B RNA molecule,
- wherein the external guide sequence promotes RNAse P-mediated cleavage of the hepatitis B RNA molecule.
A method of inhibiting hepatitis B virus comprising administering to cells an engineered expression vector encoding an external guide sequence comprising
- a RNAse P cleavage targeting sequence, and
- a recognition sequence complementary to a targeted sequence in a hepatitis B RNA molecule,
- wherein the external guide sequence promotes RNAse P-mediated cleavage of the hepatitis B RNA molecule.
Dependencies are inferred from the claim text.