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Improved serum stability and biophysical properties of siRNAs following chemical modifications

Biotechnology Letters volume 30, pages 1901–1908 (2008)Cite this article

Abstract

Small interfering RNAs (siRNAs) which mediate sequence-specific gene silencing through RNA interference have been harnessed for therapeutic applications. Here, we found combinations of modest 2′-ribose siRNA modifications that permit effective gene silencing and improve siRNA stability in human serum. Introduction of as few as two different or identical 2′-ribose modifications at a specific position of either strand, which has been previously suggested to suppress unintended off-target effects, enhances the thermal and thermodynamic stability of siRNA duplexes, and does not alter the overall A-form helical geometry that is required for silencing activity. Our results provide a useful template for the design for therapeutic siRNAs.

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Acknowledgements

We are grateful to Prof. S. S. Park for critical reading of this manuscript. This research was supported by a grant (07132KFDA689) from the Korea Food and Drug Administration, in 2007.

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Authors and Affiliations

  1. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, South Korea

    Ik Sang Cho, Jung Kim, Do Hwan Lim, Hyunggee Kim & Young Sik Lee

  2. Advanced Analysis Center, Korea Institute of Science and Technology, Seoul, 136-791, South Korea

    Hee-Chul Ahn & Kang-Bong Lee

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  1. Ik Sang Cho
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  2. Jung Kim
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  3. Do Hwan Lim
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  4. Hee-Chul Ahn
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  5. Hyunggee Kim
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  7. Young Sik Lee
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Correspondence to Young Sik Lee.

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Ik Sang Cho and Jung Kim contributed equally to this work.

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Cho, I.S., Kim, J., Lim, D.H. et al. Improved serum stability and biophysical properties of siRNAs following chemical modifications. Biotechnol Lett 30, 1901–1908 (2008). https://doi.org/10.1007/s10529-008-9776-4

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  • DOI: https://doi.org/10.1007/s10529-008-9776-4

Keywords

  • A-form helix
  • Melting temperature
  • 2′-Ribose modification
  • RNA interference
  • siRNA
  • Stability