The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect
Open accessAbstract
Short interfering RNA (siRNA)-based RNA interference (RNAi) is widely used for target gene knockdown in mammalian cells. To clarify the position-dependent functions of ribonucleotides in siRNA, siRNAs with various DNA substitutions were constructed. The following could be simultaneously replaced with DNA without substantial loss of gene-silencing activity: the seed arm, which occupies positions 2-8 from the 5'end of the guide strand; its complementary sequence; the 5'end of the guide strand and the 3'overhang of the passenger strand. However, most part of the 3' two-thirds of the guide strand could not be replaced with DNA, possibly due to binding of RNA-recognition proteins such as TRBP2 and Ago2. The passenger strand with DNA in the 3'end proximal region was incapable of inducing off-target effect. Owing to lesser stability of DNA-RNA hybrid than RNA duplex, modified siRNAs with DNA substitution in the seed region were, in most cases, incapable to exert unintended gene silencing due to seed sequence homology. Thus, it may be possible to design DNA-RNA chimeras which effectively silence mammalian target genes without silencing unintended genes.
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Expression profiling reveals off-target gene regulation by RNAi
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Predicting DNA duplex stability from the base sequence
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Improved free-energy parameters for predictions of RNA duplex stability.
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Illuminating the silence: understanding the structure and function of small RNAs
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3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets
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Thermodynamic parameters to predict stability of RNA/DNA hybrid duplexes
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BackgroundMethod
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Bramsen, J. B., Laursen, M. B., Nielsen, A. F., Hansen, T. B., Bus, C., Langkjær, N., Babu, B. R., Højland, T., Abramov, M., Van Aerschot, A., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp106 · Cited by 369
Engineering RNA for Targeted siRNA Delivery and Medical Application
Guo, P., Coban, O., Snead, N. M., Trebley, J., Hoeprich, S., Guo, S., & Shu, Y. (2010) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2010.03.008 · Cited by 300
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Metadata
- Authors
- Ui-Tei, K., Naito, Y., Zenno, S., Nishi, K., Yamato, K., Takahashi, F., Juni, A., & Saigo, K.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-02-11
- Volume
- 36
- Issue
- 7
- Pages
- 2136-2151
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2161872337
- Cited by
- 176
- References
- 8
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- gold
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- Ui-Tei, K., Naito, Y., Zenno, S., Nishi, K., Yamato, K., Takahashi, F., Juni, A., & Saigo, K. (2008). Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. Nucleic Acids Research. https://doi.org/10.1093/nar/gkn042
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