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

Hayden Peacock; Raymond V. Fucini; Prasanna Jayalath; José M. Ibarra-Soza; Henry J. Haringsma; W. Michael Flanagan; Aarron Willingham; Peter A. Beal

doi:10.1021/ja202492e

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

Hayden Peacock, Raymond V. Fucini, Prasanna Jayalath, José M. Ibarra-Soza, Henry J. Haringsma, W. Michael Flanagan, Aarron Willingham, Peter A. Beal

Chemistry

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

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.

Original language	English (US)
Pages (from-to)	9200-9203
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	133
Issue number	24
DOIs	https://doi.org/10.1021/ja202492e
State	Published - Jun 22 2011

ASJC Scopus subject areas

Chemistry(all)
Catalysis
Biochemistry
Colloid and Surface Chemistry

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10.1021/ja202492e

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Nucleobase and ribose modifications control immunostimulation by a MicroRNA-122-mimetic RNA. / Peacock, Hayden; Fucini, Raymond V.; Jayalath, Prasanna; Ibarra-Soza, José M.; Haringsma, Henry J.; Flanagan, W. Michael; Willingham, Aarron; Beal, Peter A.

In: Journal of the American Chemical Society, Vol. 133, No. 24, 22.06.2011, p. 9200-9203.

Research output: Contribution to journal › Article › peer-review

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