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Nucleic Acid Ther. 2012 Apr;22(2):90-5. doi: 10.1089/nat.2011.0333. Epub 2012 Mar 8.

In vivo activity and duration of short interfering RNAs containing a synthetic 5'-phosphate.

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1
Sirna Therapeutics, San Francisco, California, USA. denise.kenski@healthinteractions.com

Abstract

Endogenous and exogenous short interfering RNAs (siRNAs) require a 5'-phosphate for loading into Ago2 and cleavage of the target mRNA. We applied a synthetic 5'-phosphate to siRNA guide strands to evaluate if phosphorylation in vivo is rate limiting for maximal siRNA knockdown and duration. We report, for the first time, an in vivo evaluation of siRNAs with a synthetic 5'-phosphate compared to their unphosphorylated versions. siRNAs that contained a 5'-phosphate had the same activity in vivo compared with unphosphorylated siRNAs, indicating phosphorylation of an siRNA is not a rate limiting step in vivo.

PMID:
22400991
DOI:
10.1089/nat.2011.0333
[Indexed for MEDLINE]
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