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Nucleobase and ribose modifications control immunostimulation by a microRNA-122-mimetic RNA.


ABSTRACT: 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.

SUBMITTER: Peacock H 

PROVIDER: S-EPMC3116021 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Nucleobase and ribose modifications control immunostimulation by a microRNA-122-mimetic RNA.

Peacock Hayden H   Fucini Raymond V RV   Jayalath Prasanna P   Ibarra-Soza José M JM   Haringsma Henry J HJ   Flanagan W Michael WM   Willingham Aarron A   Beal Peter A PA  

Journal of the American Chemical Society 20110601 24


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 miRN  ...[more]

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