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US 11,414,657 B2Granted
Modified CRISPR RNA and modified single CRISPR RNA and uses thereof
AssigneeIonis Pharmaceuticals, Inc.
InventorsMeghdad Rahdar, Thazha P. Prakash, Eric E. Swayze, C. Frank Bennett
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Abstract
The present disclosure provides compounds comprising modified oligonucleotides for use in CRISPR. In certain embodiments, such modified oligonucleotides provide improved properties of crRNA. In certain embodiments, such modified oligonucleotides provide improved properties of scrRNA.
Claims12
A modified crRNA consisting essentially of 29 to 32 nucleosides, wherein each internucleoside linkage is a phosphorothioate internucleoside linkage, wherein:
- a. a first portion of the crRNA is a DNA recognition portion, and
- b. a second portion of the crRNA is a tracrRNA recognition portion having at least one nucleoside that comprises a bicyclic sugar moiety,
- wherein
- the DNA recognition portion is located 5′ of the tracrRNA recognition portion,
- the seven 5′-terminal nucleosides of the DNA recognition portion comprise modified sugar moieties, at least one of which is a non-bicyclic sugar moiety,
- the DNA recognition portion comprises at least 10 consecutive nucleosides comprising unmodified 2′-hydroxy sugar moieties at the 3′ end of the DNA recognition portion, and
- the 5′ end of the tracrRNA recognition portion comprises the motif kr3 wherein k is a cEt sugar moiety and r is an unmodified 2′-hydroxy sugar moiety.
4 more elements
Dependencies are inferred from the claim text.