Unique gene-silencing and structural properties of 2′-fluoro-modified siRNAs

Muthiah Manoharan; Akin Akinc; Rajendra K. Pandey; June Qin; Philipp Hadwiger; Matthias John; Kathy Mills; Klaus Charisse; Martin A. Maier; Lubomir Nechev; Emily M. Greene; Pradeep S. Pallan; Eriks Rozners; Kallanthottathil G. Rajeev; Martin Egli

doi:10.1002/anie.201006519

Unique gene-silencing and structural properties of 2′-fluoro-modified siRNAs

Muthiah Manoharan
, Akin Akinc
, Rajendra K. Pandey
, June Qin
, Philipp Hadwiger
, Matthias John
, Kathy Mills
, Klaus Charisse
, Martin A. Maier
, Lubomir Nechev
, Emily M. Greene
, Pradeep S. Pallan
, Eriks Rozners
, Kallanthottathil G. Rajeev
, Martin Egli

Chemistry

Binghamton University

Alnylam Pharmaceuticals
F. Hoffmann-La Roche AG
State University of New York Binghamton University
Vanderbilt University

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

174 Scopus citations

Abstract

(Figure Presented) With little or no negative impact on the activity of small interfering RNAs (siRNAs), regardless of the number of modifications or the positions within the strand, the 2′-deoxy-2′-fluoro (2′-F) modification is unique. Furthermore, the 2′-F-modified siRNA (see crystal structure) was thermodynamically more stable and more nuclease-resistant than the parent siRNA, and produced no immunostimulatory response.

Original language	English
Pages (from-to)	2284-2288
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	50
Issue number	10
DOIs	https://doi.org/10.1002/anie.201006519
State	Published - Mar 1 2011

Keywords

Drug discovery
Nucleic acid modification
RNA interference
Thermodynamics
X-ray crystallography

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10.1002/anie.201006519

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Manoharan, M., Akinc, A., Pandey, R. K., Qin, J., Hadwiger, P., John, M., Mills, K., Charisse, K., Maier, M. A., Nechev, L., Greene, E. M., Pallan, P. S., Rozners, E., Rajeev, K. G., & Egli, M. (2011). Unique gene-silencing and structural properties of 2′-fluoro-modified siRNAs. Angewandte Chemie - International Edition, 50(10), 2284-2288. https://doi.org/10.1002/anie.201006519

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title = "Unique gene-silencing and structural properties of 2′-fluoro-modified siRNAs",

abstract = "(Figure Presented) With little or no negative impact on the activity of small interfering RNAs (siRNAs), regardless of the number of modifications or the positions within the strand, the 2′-deoxy-2′-fluoro (2′-F) modification is unique. Furthermore, the 2′-F-modified siRNA (see crystal structure) was thermodynamically more stable and more nuclease-resistant than the parent siRNA, and produced no immunostimulatory response.",

keywords = "Drug discovery, Nucleic acid modification, RNA interference, Thermodynamics, X-ray crystallography",

author = "Muthiah Manoharan and Akin Akinc and Pandey, \{Rajendra K.\} and June Qin and Philipp Hadwiger and Matthias John and Kathy Mills and Klaus Charisse and Maier, \{Martin A.\} and Lubomir Nechev and Greene, \{Emily M.\} and Pallan, \{Pradeep S.\} and Eriks Rozners and Rajeev, \{Kallanthottathil G.\} and Martin Egli",

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doi = "10.1002/anie.201006519",

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T1 - Unique gene-silencing and structural properties of 2′-fluoro-modified siRNAs

AU - Manoharan, Muthiah

AU - Akinc, Akin

AU - Pandey, Rajendra K.

AU - Qin, June

AU - Hadwiger, Philipp

AU - John, Matthias

AU - Mills, Kathy

AU - Charisse, Klaus

AU - Maier, Martin A.

AU - Nechev, Lubomir

AU - Greene, Emily M.

AU - Pallan, Pradeep S.

AU - Rozners, Eriks

AU - Rajeev, Kallanthottathil G.

AU - Egli, Martin

PY - 2011/3/1

Y1 - 2011/3/1

N2 - (Figure Presented) With little or no negative impact on the activity of small interfering RNAs (siRNAs), regardless of the number of modifications or the positions within the strand, the 2′-deoxy-2′-fluoro (2′-F) modification is unique. Furthermore, the 2′-F-modified siRNA (see crystal structure) was thermodynamically more stable and more nuclease-resistant than the parent siRNA, and produced no immunostimulatory response.

AB - (Figure Presented) With little or no negative impact on the activity of small interfering RNAs (siRNAs), regardless of the number of modifications or the positions within the strand, the 2′-deoxy-2′-fluoro (2′-F) modification is unique. Furthermore, the 2′-F-modified siRNA (see crystal structure) was thermodynamically more stable and more nuclease-resistant than the parent siRNA, and produced no immunostimulatory response.

KW - Drug discovery

KW - Nucleic acid modification

KW - RNA interference

KW - Thermodynamics

KW - X-ray crystallography

UR - https://www.scopus.com/pages/publications/79952066733

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DO - 10.1002/anie.201006519

M3 - Article

C2 - 21351337

SN - 1433-7851

VL - 50

SP - 2284

EP - 2288

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 10

ER -

Unique gene-silencing and structural properties of 2′-fluoro-modified siRNAs

Abstract

Keywords

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