Chemical Synthesis of 2′-O-Alkylated siRNAs

  • Joachim W. Engels
  • Dalibor Odadzic
  • Romualdas Smicius
  • Jens Haas
Part of the Methods in Molecular Biology book series (MIMB, volume 623)


Chemical synthesis has been a major endeavor to create active siRNAs. The downregulation of mRNA by 21-mer double-stranded siRNAs can be improved by using modified nucleotides, especially 2′-O-alkylated ones. Besides the commercially available 2¢-O-methyl ribosides, 2′-alkyl groups bearing positive charges are especially promising candidates. We have shown that in a proper formulation they are superior to unmodified siRNAs. This may be due to enhanced stability and most probably to a better uptake into the cells.

Key words

siRNA High pressure liquid chromatography Mass spectrometry Alkylation 



The authors would like to thank S. Bernhardt and H. Brill for technical assistance and the EU Right project (LSHB-CT-2004-005476) for financial support.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Joachim W. Engels
    • 1
  • Dalibor Odadzic
    • 1
  • Romualdas Smicius
    • 2
  • Jens Haas
    • 3
  1. 1.Institute of Organic Chemistry and Chemical BiologyJ.W. Goethe-UniversitätFrankfurt am MainGermany
  2. 2.Biotherapeutics and Bioinnovation CenterColey Pharmaceutical GmbH (a Pfizer Company)DüsseldorfGermany
  3. 3.BioNTech AG c/o Department of Internal Medicine III, Experimental and Translational OncologyJohannes Gutenberg UniversityMainzGermany

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