Oligoribonucleotides and ribonucleases for cleaving RNA
AssigneeIsis Pharmaceuticals, Inc.
InventorStanley T. Crooke
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AssigneeIsis Pharmaceuticals, Inc.
InventorStanley T. Crooke
Estimating the term…
Oligomeric compounds including oligoribonucleotides and oligoribonucleosides are provided that have subsequences of 2'-pentoribofuranosyl nucleosides that activate dsRNase. The oligoribonucleotides and oligoribonucleosides can include substituent groups for increasing binding affinity to complementary nucleic acid strand as well as substituent groups for increasing nuclease resistance. The oligomeric compounds are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics. Also included in the invention are mammalian ribonucleases, i.e., enzymes that degrade RNA, and substrates for such ribonucleases. Such a ribonuclease is referred to herein as a dsRNase, wherein "ds" indicates the RNase's specificity for certain double-stranded RNA substrates. The artificial substrates for the dsRNases described herein are useful in preparing affinity matrices for purifying mammalian ribonuclease as well as non-degradative RNA-binding proteins.
A method for in vitro modification of a sequence-specific target RNA comprising contacting a test solution containing a dsRNase enzyme and said target RNA with an oligomeric compound having a sequence of nucleoside subunits capable of specifically hybridizing to said target RNA where at least one of the nucleoside subunits is modified to improve the affinity or specificity of said compound to said target RNA;
A method of concurrently enhancing hybridization and dsRNase enzyme activation in an organism comprising contacting the organism with an oligomeric compound having a sequence of nucleoside subunits capable of specifically hybridizing to a complementary strand of target RNA, where at least one of the nucleoside subunits is modified to improve at least one of:
A synthetic oligomeric compound comprising, in sequence;
A synthetic oligomeric compound comprising, in sequence;
Dependencies are inferred from the claim text.