Methods of using mammalian RNase H and compositions thereof
OwnerBrett P. Monia, Phillip Dan Cook +3inventors
InventorsBrett P. Monia, Phillip Dan Cook, Stanley T. Crooke, Walter Lima, Hongjiang Wu
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Abstract
The present invention relates to methods for using mammalian RNase H and compositions thereof, particularly for reduction of a selected cellular RNA target via antisense technology.
Claims18
A method of promoting inhibition of expression of a selected protein by an antisense oligonucleotide targeted to an RNA encoding the selected protein comprising:
- (a) providing an antisense oligonucleotide targeted to an RNA encoding a selected protein whose expression is to be inhibited, wherein said oligonucleotide is a chimeric oligonucleotide having a modification at the 2′ position of at least one sugar moiety;
- (b) allowing said oligonucleotide and said RNA to hybridize to form an oligonucleotide-RNA duplex;
- and
- (c) contacting said oligonucleotide-RNA duplex with a mammalian RNase H polypeptide, under conditions in which cleavage of the RNA strand of the oligonucleotide-RNA duplex occurs, whereby inhibition of expression of the selected protein is promoted.
A method of eliciting cleavage of a selected cellular RNA target comprising:
- (a) providing an antisense oligonucleotide targeted to a selected cellular RNA target to be cleaved, wherein said oligonucleotide is a chimeric oligonucleotide having a modification at the 2′ position of at least one sugar moiety;
- (b) allowing said oligonucleotide and said RNA to hybridize to form an oligonucleotide-RNA duplex;
- and
- (c) contacting said oligonucleotide-RNA duplex with a mammalian RNase H polypeptide, under conditions in which cleavage of the RNA strand of the oligonucleotide-RNA duplex occurs,whereby cleavage of the cellular RNA target is elicited.
A method of making an antisense oligonucleotide which elicits cleavage of its complementary target RNA by a mammalian RNase H polypeptide comprising synthesizing a chimeric oligonucleotide which has a modification at the 2′ position of at least one sugar moiety, and which is targeted to a selected RNA, wherein said oligonucleotide, when hybridized to the selected RNA target to form a duplex, will bind a mammalian RNase H polypeptide which thereby cleaves the RNA strand of the duplex.
Dependencies are inferred from the claim text.