| Literature DB >> 19282453 |
Jesper B Bramsen1, Maria B Laursen, Anne F Nielsen, Thomas B Hansen, Claus Bus, Niels Langkjaer, B Ravindra Babu, Torben Højland, Mikhail Abramov, Arthur Van Aerschot, Dalibor Odadzic, Romualdas Smicius, Jens Haas, Cordula Andree, Jharna Barman, Malgorzata Wenska, Puneet Srivastava, Chuanzheng Zhou, Dmytro Honcharenko, Simone Hess, Elke Müller, Georgii V Bobkov, Sergey N Mikhailov, Eugenio Fava, Thomas F Meyer, Jyoti Chattopadhyaya, Marino Zerial, Joachim W Engels, Piet Herdewijn, Jesper Wengel, Jørgen Kjems.
Abstract
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 RNA-induced 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 toxicity.Entities:
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Year: 2009 PMID： 19282453 PMCID： PMC2685080 DOI： 10.1093/nar/gkp106
Source DB: PubMed Journal: Nucleic Acids Res ISSN： 0305-1048 Impact factor: 16.971