Abstract
Promoter-based expression of short hairpin RNAs (shRNAs) may in principle provide stable silencing of genes in any tissue. As for all approaches that require transgene expression, safe delivery is the biggest obstacle, but toxicity can also occur via expression of the sequence itself. Innate immunity mechanisms can be triggered by expressed hairpin RNAs, critical cellular factors can be saturated, and genes other than the intended target can be silenced. Nevertheless, shRNAs constitute a valuable tool for in vivo research and have great therapeutic potential if the challenges with delivery and side effects are appropriately addressed.
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Acknowledgements
This work was supported by grants from the Norwegian Research Council and the Norwegian Functional Genomics Program (FUGE) to O.S. and US National Institutes of Health grants from the National Institute of Allergy and Infectious Diseases and National Heart, Lung and Blood Institute to J.J.R.
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Snøve, O., Rossi, J. Expressing short hairpin RNAs in vivo. Nat Methods 3, 689–695 (2006). https://doi.org/10.1038/nmeth927
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