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

Research output: Contribution to journalArticle

51 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 languageEnglish (US)
Pages (from-to)9200-9203
Number of pages4
JournalJournal of the American Chemical Society
Volume133
Issue number24
DOIs
StatePublished - Jun 22 2011

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

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    Peacock, H., Fucini, R. V., Jayalath, P., Ibarra-Soza, J. M., Haringsma, H. J., Flanagan, W. M., Willingham, A., & Beal, P. A. (2011). Nucleobase and ribose modifications control immunostimulation by a MicroRNA-122-mimetic RNA. Journal of the American Chemical Society, 133(24), 9200-9203. https://doi.org/10.1021/ja202492e