title: 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.
authors: Department of Chemistry, University of California-Davis, One Shields Avenue, Davis, California 95616, USA.
authors: Hayden
authors: H
authors: Peacock
authors: Raymond V
authors: RV
authors: Fucini
authors: Prasanna
authors: P
authors: Jayalath
authors: José M
authors: JM
authors: Ibarra-Soza
authors: Henry J
authors: HJ
authors: Haringsma
authors: W Michael
authors: WM
authors: Flanagan
authors: Aarron
authors: A
authors: Willingham
authors: Peter A
authors: PA
authors: Beal
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