Document Detail


Nucleobase and Ribose Modifications Control Immunostimulation by a MicroRNA-122-mimetic RNA.
MedLine Citation:
PMID:  21612237     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Immune stimulation is a significant hurdle in the development of effective and safe RNA interference therapeutics. Here, we address this problem in the context of a mimic of microRNA-122 by employing novel nucleobase and known 2'-ribose modifications. The nucleobase modifications are analogues of adenosine and guanosine that contain cyclopentyl and propyl minor-groove projections. Via a site-by-site chemical modification analysis, we identify several immunostimulatory 'hot spots' within the miRNA guide strand at which single base modifications significantly reduce immune stimulation. A duplex containing one base modification on each strand proved to be most effective in preventing immune stimulation.
Authors:
Hayden Peacock; Raymond V Fucini; Prasanna Jayalath; José M Ibarra-Soza; Henry J Haringsma; W Michael Flanagan; Aarron Willingham; Peter A Beal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-25
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  -     ISSN:  1520-5126     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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