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

50 Citations (Scopus)

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

Fingerprint

Ribose
Chemical modification
RNA
MicroRNAs
Immunization
Guanosine
RNA Interference
Adenosine
Therapeutics

ASJC Scopus subject areas

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

Cite this

Peacock, H., Fucini, R. V., Jayalath, P., Ibarra-Soza, J. M., Haringsma, H. J., Flanagan, W. M., ... 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

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 journalArticle

Peacock, H, Fucini, RV, Jayalath, P, Ibarra-Soza, JM, Haringsma, HJ, Flanagan, WM, Willingham, A & Beal, PA 2011, 'Nucleobase and ribose modifications control immunostimulation by a MicroRNA-122-mimetic RNA', Journal of the American Chemical Society, vol. 133, no. 24, pp. 9200-9203. https://doi.org/10.1021/ja202492e
Peacock H, Fucini RV, Jayalath P, Ibarra-Soza JM, Haringsma HJ, Flanagan WM et al. Nucleobase and ribose modifications control immunostimulation by a MicroRNA-122-mimetic RNA. Journal of the American Chemical Society. 2011 Jun 22;133(24):9200-9203. https://doi.org/10.1021/ja202492e
Peacock, Hayden ; Fucini, Raymond V. ; Jayalath, Prasanna ; Ibarra-Soza, José M. ; Haringsma, Henry J. ; Flanagan, W. Michael ; Willingham, Aarron ; Beal, Peter A. / Nucleobase and ribose modifications control immunostimulation by a MicroRNA-122-mimetic RNA. In: Journal of the American Chemical Society. 2011 ; Vol. 133, No. 24. pp. 9200-9203.
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