Nucleobase and Ribose Modifications Control Immunostimulation by a MicroRNA-122-mimetic RNA
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- 作者：Hayden Peacock ; Raymond V. Fucini ; Prasanna Jayalath ; Jos茅 M. Ibarra-Soza ; Henry J. Haringsma ; W. Michael Flanagan ; Aarron Willingham ; Peter A. Beal
- 刊名：Journal of the American Chemical Society
- 出版年：2011
- 出版时间：June 22, 2011
- 年：2011
- 卷：133
- 期：24
- 页码：9200-9203
- 全文大小：787K
- 年卷期：v.133,no.24(June 22, 2011)
- ISSN：1520-5126
文摘
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鈥?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 鈥榟ot spots鈥?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.