1345562-35-7Relevant academic research and scientific papers
Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom
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, (2016/05/19)
The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
Identification of metabolically stable 5′-phosphate analogs that support single-stranded siRNA activity
Prakash, Thazha P.,Lima, Walt F.,Murray, Heather M.,Li, Wenyu,Kinberger, Garth A.,Chappell, Alfred E.,Gaus, Hans,Seth, Punit P.,Bhat, Balkrishen,Crooke, Stanley T.,Swayze, Eric E.
, p. 2993 - 3011 (2015/10/05)
The ss-siRNA activity in vivo requires a metabolically stable 5′-phosphate analog. In this report we used crystal structure of the 5′-phosphate binding pocket of Ago-2 bound with guide strand to design and synthesize ss-siRNAs containing various 5′-phosphate analogs. Our results indicate that the electronic and spatial orientation of the 5′-phosphate analog was critical for ss-siRNA activity. Chemically modified sssiRNA targeting human apoC III mRNA demonstrated good potency for inhibiting ApoC III mRNA and protein in transgenicmice. Moreover, ApoC III ss-siRNAs were able to reduce the triglyceride and LDL cholesterol in transgenic mice demonstrating pharmacological effect of ss-siRNA. Our study provides guidance to develop surrogate phosphate analog for ss-siRNA and demonstrates that ss-siRNA provides an alternative strategy for therapeutic gene silencing.
COMPOSITIONS AND METHODS FOR MODULATION OF TARGET NUCLEIC ACIDS
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, (2015/01/07)
The present disclosure pertains generally to chemically-modified oligonucleotides for use in research, diagnostics, and/or therapeutics. In certain embodiments, the present disclosure describes compounds and methods for the modulation of a target nucleic
5' MODIFIED NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM
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Paragraph 0878, (2013/05/21)
The present invention provides 5′ modified nucleosides and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides having at least one 5′-substituent and an optional 2′ substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
