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Updated: May 24, 2026

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
Published on: September 5, 2016
In vivo activity and duration of short interfering RNAs containing a synthetic 5'-phosphate
Denise M Kenski1, Aarron T Willingham, Henry J Haringsma
1Sirna 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.
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