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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: Publikationen MPI-CBG 2009 arch     Display Documents

ID: 463164.0, MPI für molekulare Zellbiologie und Genetik / Publikationen MPI-CBG 2009 arch
A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity
Authors:Bramsen, Jesper B.; Laursen, Maria B.; Nielsen, Anne F.; Hansen, Thomas B.; Bus, Claus; Langkjær, Niels; Babu, B. Ravindra; Højland, Torben; Abramov, Mikhail; Aerschot, Arthur Van; Odadzic, Dalibor; Smicius, Romualdas; Haas, Jens; Andree, Cordula; Barman, Jharna; Wenska, Malgorzata; Srivastava, Puneet; Zhou, Chuanzheng; Honcharenko, Dmytro; Hess, Simone; Müller, Elke; Bobkov, Georgii V.; Mikhailov, Sergey N.; Fava, Eugenio; Meyer, Thomas F.; Chattopadhyaya, Jyoti; Zerial, Marino; Engels, Joachim W.; Herdewijn, Piet; Wengel, Jesper; Kjems, Jørgen
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Nucleic Acids Research
Issue / Number:9
Start Page:2867
End Page:2881
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:The use of chemically synthesized short interfering
RNAs (siRNAs) is currently the method of choice
to manipulate gene expression in mammalian cell
culture, yet improvements of siRNA design is
expectably required for successful application
in vivo. Several studies have aimed at improving
siRNA performance through the introduction of
chemical modifications but a direct comparison of
these results is difficult. We have directly compared
the effect of 21 types of chemical modifications
on siRNA activity and toxicity in a total of 2160
siRNA duplexes. We demonstrate that siRNA activity
is primarily enhanced by favouring the incorporation
of the intended antisense strand during RNAinduced
silencing complex (RISC) loading by modulation
of siRNA thermodynamic asymmetry and
engineering of siRNA 3’-overhangs. Collectively,
our results provide unique insights into the tolerance
for chemical modifications and provide a
simple guide to successful chemical modification
of siRNAs with improved activity, stability and low
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für molekulare Zellbiologie und Genetik
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