Format

Send to:

Choose Destination
See comment in PubMed Commons below
BMC Genomics. 2007 Apr 19;8:106.

Novel insights into RNAi off-target effects using C. elegans paralogs.

Author information

  • 1Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. JRUAL@PARTNERS.ORG

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.

PMID:
17445269
[PubMed - indexed for MEDLINE]
PMCID:
PMC1868761
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk