Improved serum stability and biophysical properties of siRNAs following chemical modifications

Ik Sang Cho, Jung Kim, Do Hwan Lim, Hee Chul Ahn, Hyunggee Kim, Kang Bong Lee, Young Sik Lee

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1901-1908
Number of pages8
JournalBiotechnology letters
Issue number11
Publication statusPublished - 2008 Nov

Bibliographical note

Funding Information:
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.


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

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology


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