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A large-scale chemical modification screen identifies des...
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Claus Bus
A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity
Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review
- Jesper B Bramsen
- Maria Bach Laursen, Danmark
- Anne F Nielsen
- Thomas B Hansen, Danmark
- Claus Bus
- Niels Langkjær, Syddansk Universitet, Danmark
- Bolle Ravindra Babu, Syddansk Universitet, Danmark
- Torben Højland, Syddansk Universitet, Danmark
- Mikhail Abramov, KU Leuven, Belgien
- Arthur Van Aerschot, KU Leuven, Belgien
- Dalibor Odadzic, Goethe University Frankfurt, Tyskland
- Romualdas Smicius, Goethe University Frankfurt, Tyskland
- Jens Haas, Goethe University Frankfurt, Tyskland
- Cordula Andree, Max Planck Institute of Molecular Cell Biology and Genetics, Tyskland
- Jharna Barman, Uppsala University, Sverige
- Malgorzata Wenska, Uppsala University, Sverige
- Puneet Srivastava, Uppsala University, Sverige
- Chuanzheng Zhou, Uppsala University, Sverige
- Dmytro Honcharenko, Uppsala University, Sverige
- Simone Hess, Department of Molecular Biology, Max Planck Institute for Infection Biology, Tyskland
- Elke Müller, Department of Molecular Biology, Max Planck Institute for Infection Biology, Tyskland
- Georgii V Bobkov, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Rusland
- Sergey N Mikhailov, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Rusland
- Eugenio Fava, Max Planck Institute of Molecular Cell Biology and Genetics, Tyskland
- Thomas F Meyer, Department of Molecular Biology, Max Planck Institute for Infection Biology, BerlinDepartment of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Tyskland
- Jyoti Chattopadhyaya, Uppsala University, Sverige
- Marino Zerial, Max Planck Institute of Molecular Cell Biology and Genetics, Tyskland
- Joachim W Engels, Goethe University Frankfurt, Tyskland
- Piet Herdewijn, KU Leuven, Belgien
- Jesper Wengel, Syddansk Universitet, Danmark
- Jørgen Kjems
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nucleic Acids Research |
| Vol/bind | 37 |
| Nummer | 9 |
| Sider (fra-til) | 2867-81 |
| Antal sider | 15 |
| ISSN | 0305-1048 |
| DOI | |
| Status | Udgivet - 2009 |
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