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 | |
| State | Published - Jun 22 2011 |
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ASJC Scopus subject areas
- Chemistry(all)
- Catalysis
- Biochemistry
- Colloid and Surface Chemistry
Cite this
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
}
TY - JOUR
T1 - Nucleobase and ribose modifications control immunostimulation by a MicroRNA-122-mimetic RNA
AU - Peacock, Hayden
AU - Fucini, Raymond V.
AU - Jayalath, Prasanna
AU - Ibarra-Soza, José M.
AU - Haringsma, Henry J.
AU - Flanagan, W. Michael
AU - Willingham, Aarron
AU - Beal, Peter A.
PY - 2011/6/22
Y1 - 2011/6/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79959199054&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959199054&partnerID=8YFLogxK
U2 - 10.1021/ja202492e
DO - 10.1021/ja202492e
M3 - Article
C2 - 21612237
AN - SCOPUS:79959199054
VL - 133
SP - 9200
EP - 9203
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 24
ER -