Oligonucleotides having A-DNA form and B-DNA form conformational geometry
AssigneeIsis Pharmaceuticals, Inc.
InventorsMuthiah Manoharan, Venkatraman Mohan, Phillip Dan Cook, Andrew M. Kawasaki
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AssigneeIsis Pharmaceuticals, Inc.
InventorsMuthiah Manoharan, Venkatraman Mohan, Phillip Dan Cook, Andrew M. Kawasaki
Estimating the term…
Modified oligonucleotides containing both A-form conformation geometry and B-from conformation geometry nucleotides are disclosed. The B-form geometry allows the oligonucleotide to serve as substrates for RNase H when bound to a target nucleic acid strand. The A-form geometry imparts properties to the oligonucleotide that modulate binding affinity and nuclease resistance. By utilizing C2′ endo sugars or O4′ endo sugars, the B-form characteristics are imparted to a portion of the oligonucleotide. The A-form characteristics are imparted via use of either 2′-O-modified nucleotides that have 3′ endo geometries or use of end caps having particular nuclease stability or by use of both of these in conjunction with each other.
An oligonucleotide comprising a plurality of nucleotides, wherein:
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