The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Off-target effects by siRNA can induce toxic phenotype
Open accessAbstract
Although recent microarray studies have provided evidence of RNA interference (RNAi)-mediated off-target gene modulation, little is known about whether these changes induce observable phenotypic outcomes. Here we show that a fraction of randomly selected small inhibitory RNAs (siRNAs) can induce changes in cell viability in a target-independent fashion. The observed toxicity requires an intact RNAi pathway and can be eliminated by the addition of chemical modifications that reduce off-target effects. Furthermore, an analysis of toxic and nontoxic duplexes identifies a strong correlation between the toxicity and the presence of a 4-base-pair motif (UGGC) in the RISC-entering strand of toxic siRNA. This article provides further evidence of siRNA-induced off-target effects generating a measurable phenotype and also provides an example of how such undesirable phenotypes can be mitigated by addition of chemical modifications to the siRNA.
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Cites
Expression profiling reveals off-target gene regulation by RNAi
Jackson, A. L., Bartz, S. R., Schelter, J., Kobayashi, S. V., Burchard, J., Mao, M., Li, B., Cavet, G., & Linsley, P. S. (2003) · Nature Biotechnology · doi:10.1038/nbt831 · Cited by 2,370
Rational siRNA design for RNA interference
Reynolds, A., Leake, D., Boese, Q., Scaringe, S., Marshall, W. S., & Khvorova, A. (2004) · Nature Biotechnology · doi:10.1038/nbt936 · Cited by 2,094
Self-citation3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets
Birmingham, A., Anderson, E. M., Reynolds, A., Ilsley-Tyree, D., Leake, D., Fedorov, Y., Baskerville, S., Maksimova, E., Robinson, K., Karpilow, J., et al. (2006) · Nature Methods · doi:10.1038/nmeth854 · Cited by 920
Self-citation
Cited by
Induced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486
siRNA versus miRNA as therapeutics for gene silencing
Lam, J. K. W., Chow, M. Y. T., Zhang, Y., & Leung, S. W. S. (2015) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.23 · Cited by 1,081
RNAi therapeutics: Principles, prospects and challenges
Aagaard, L., & Rossi, J. J. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.03.005 · Cited by 895
Silencing disease genes in the laboratory and the clinic
Watts, J. K., & Corey, D. R. (2012) · The Journal of Pathology · doi:10.1002/path.2993 · Cited by 470
Distance constraints between microRNA target sites dictate efficacy and cooperativity
Sætrom, P., Heale, B. S. E., Snøve, O., Aagaard, L., Alluin, J., & Rossi, J. J. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm133 · Cited by 375
Metadata
- Authors
- Fedorov, Y., Anderson, E. M., Birmingham, A., Reynolds, A., Karpilow, J., Robinson, K., Leake, D., Marshall, W. S., & Khvorova, A.
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-05-08
- Volume
- 12
- Issue
- 7
- Pages
- 1188-1196
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- OpenAlex
- W2144510218
- Cited by
- 490
- References
- 3
- FWCI
- 15.10
- Type
- journal article
- Language
- en
- Open access
- bronze
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