Novel Insights into RNAi Off-Target Effects Using C. elegans Paralogs

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Novel Insights into RNAi Off-Target Effects Using C. elegans Paralogs

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Title: Novel Insights into RNAi Off-Target Effects Using C. elegans Paralogs
Author: Klitgord, Niels; Achaz, Guillaume; Rual, Jean-Francois

Note: Order does not necessarily reflect citation order of authors.

Citation: Rual, Jean-François, Niels Klitgord, and Guillaume Achaz. 2007. Novel insights into RNAi off-target effects using C. elegans paralogs. BMC Genomics 8:106.
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Abstract: Background: In the few years since its discovery, RNAi has turned into a very powerful tool for the study of gene function by allowing post-transcriptional gene silencing. The RNAi mechanism, which is based on the introduction of a double-stranded RNA (dsRNA) trigger whose sequence is similar to that of the targeted messenger RNA (mRNA), is subject to off-target cross-reaction. Results: We use a novel strategy based on phenotypic analysis of paralogs and predict that, in Caenorhabditis elegans, off-target effects occur when an mRNA sequence shares more than 95% identity over 40 nucleotides with the dsRNA. Interestingly, our results suggest that the minimum length necessary of a high-similarity stretch between a dsRNA and its target in order to observe an efficient RNAi effect varies from 30 to 50 nucleotides rather than 22 nucleotides, which is the length of siRNAs in C. elegans. Conclusion: Our predictive methods would improve the design of dsRNA and ultimately the use of RNAi as a therapeutic tool upon experimental verification.
Published Version: doi: 10.1186/1471-2164-8-106
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868761/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4621129

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