Unique Gene-Silencing and Structural Properties of 2′-Fluoro-Modified siRNAs


  • We are grateful to the U.S. National Institutes of Health for continuous support (R01 GM055237 to M.E. and R01 GM071461 to E.R.). Vanderbilt University is a member institution of LS-CAT at the APS, Argonne, IL. Use of the APS at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. siRNA=small interfering RNA.


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With little or no negative impact on the activity of small interfering RNAs (siRNAs), regardless of the number of modifications or the positions within the strand, the 2′-deoxy-2′-fluoro (2′-F) modification is unique. Furthermore, the 2′-F-modified siRNA (see crystal structure) was thermodynamically more stable and more nuclease-resistant than the parent siRNA, and produced no immunostimulatory response.