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  • Bramsen, Jesper B. (author)

A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity

  • Article/chapterEnglish2009

Publisher, publication year, extent ...

  • 2009-03-12
  • Oxford University Press,2009
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-106722
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-106722URI
  • https://doi.org/10.1093/nar/gkp106DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:118832782URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Laursen, Maria B (author)
  • Nielsen, Anne F. (author)
  • Hansen, Thomas B. (author)
  • Bus, Claus (author)
  • Langkjær, Niels (author)
  • Babu, B. Ravindra (author)
  • Højland, Torben (author)
  • Abramov, Mikhail (author)
  • van Aerschot, Arthur (author)
  • Odadzic, Dalibor (author)
  • Smicius, Romualdas (author)
  • Haas, Jens (author)
  • Andree, Cordula (author)
  • Barman, JharnaUppsala universitet,Institutionen för bioorganisk kemi (author)
  • Wenska, MalgorzataKarolinska Institutet,Uppsala universitet,Institutionen för bioorganisk kemi (author)
  • Srivastava, PuneetUppsala universitet,Institutionen för bioorganisk kemi(Swepub:uu)pusri933 (author)
  • Zhou, ChuanzhengUppsala universitet,Institutionen för bioorganisk kemi(Swepub:uu)zhchu839 (author)
  • Honcharenko, DmytroUppsala universitet,Institutionen för bioorganisk kemi(Swepub:uu)dmhon031 (author)
  • Hess, Simone (author)
  • Müller, Elke (author)
  • Bobkov, Georgii V. (author)
  • Mikhailov, Sergey N. (author)
  • Fava, Eugenio (author)
  • Meyer, Thomas F. (author)
  • Chattopadhyaya, JyotiUppsala universitet,Institutionen för bioorganisk kemi(Swepub:uu)jyotchat (author)
  • Zerial, Marino (author)
  • Engels, Joachim W. (author)
  • Herdewijn, Piet (author)
  • Wengel, Jesper (author)
  • Kjems, Jørgen (author)
  • Uppsala universitetInstitutionen för bioorganisk kemi (creator_code:org_t)

Related titles

  • In:Nucleic Acids Research: Oxford University Press37:9, s. 2867-28810305-10481362-4962

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