The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Position-specific chemical modification of siRNAs reduces “off-target” transcript silencing
Open accessAbstract
Transfected siRNAs regulate numerous transcripts sharing limited complementarity to the RNA duplex. This unintended (“off-target”) silencing can hinder the use of RNAi to define gene function. Here we describe position-specific, sequence-independent chemical modifications that reduced silencing of partially complementary transcripts by all siRNAs tested. Silencing of perfectly matched targets was unaffected by these modifications. The chemical modification also reduced off-target phenotypes in growth inhibition studies. Key to the modification was 2′-O-methyl ribosyl substitution at position 2 in the guide strand, which reduced silencing of most off-target transcripts with complementarity to the seed region of the siRNA guide strand. The sharp position dependence of 2′-O-methyl ribosyl modification contrasts with the broader position dependence of base-pair substitutions within the seed region, suggesting a role for position 2 of the guide strand distinct from its effects on pairing to target transcripts.
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Cites
Mfold web server for nucleic acid folding and hybridization prediction
Zuker, M. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg595 · Cited by 13,404
Improved tools for biological sequence comparison.
Pearson, W. R., & Lipman, D. J. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.8.2444 · Cited by 11,227
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
Self-citationTolerance for mutations and chemical modifications in a siRNA
Amarzguioui, M. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg147 · Cited by 534
Cited by
Predicting effective microRNA target sites in mammalian mRNAs
Agarwal, V., Bell, G. W., Nam, J.-W., & Bartel, D. P. (2015) · eLife · doi:10.7554/elife.05005 · Cited by 7,318
Knocking down barriers: advances in siRNA delivery
Whitehead, K. A., Langer, R., & Anderson, D. G. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2742 · Cited by 3,115
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Legnini, I., Di Timoteo, G., Rossi, F., Morlando, M., Briganti, F., Sthandier, O., Fatica, A., Santini, T., Andronache, A., Wade, M., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.017 · Cited by 2,173
The current state and future directions of RNAi-based therapeutics
Setten, R. L., Rossi, J. J., & Han, S.-P. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0017-4 · Cited by 1,443
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Khvorova, A., & Watts, J. K. (2017) · Nature Biotechnology · doi:10.1038/nbt.3765 · Cited by 1,216
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Metadata
- Authors
- Jackson, A. L., Burchard, J., Leake, D., Reynolds, A., Schelter, J., Guo, J., Johnson, J. M., Lim, L., Karpilow, J., Nichols, K., Marshall, W., Khvorova, A., & Linsley, P. S.
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-05-08
- Volume
- 12
- Issue
- 7
- Pages
- 1197-1205
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- OpenAlex
- W2143313350
- Cited by
- 789
- References
- 4
- FWCI
- 24.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Jackson, A. L., Burchard, J., Leake, D., Reynolds, A., Schelter, J., Guo, J., Johnson, J. M., Lim, L., Karpilow, J., Nichols, K., Marshall, W., Khvorova, A., & Linsley, P. S. (2006). Position-specific chemical modification of siRNAs reduces “off-target” transcript silencing. RNA. https://doi.org/10.1261/rna.30706
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