The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
RNA Interference in Mammalian Cells by Chemically-Modified RNA
Abstract
RNA interference (RNAi) is proving to be a robust and versatile technique for controlling gene expression in mammalian cells. To fully realize its potential in vivo, however, it may be necessary to introduce chemical modifications to optimize potency, stability, and pharmacokinetic properties. Here, we test the effects of chemical modifications on RNA stability and inhibition of gene expression. We find that RNA duplexes containing either phosphodiester or varying numbers of phosphorothioate linkages are remarkably stable during prolonged incubations in serum. Treatment of cells with RNA duplexes containing phosphorothioate linkages leads to selective inhibition of gene expression. RNAi also tolerates the introduction of 2'-deoxy-2'-fluorouridine or locked nucleic acid (LNA) nucleotides. Introduction of LNA nucleotides also substantially increases the thermal stability of modified RNA duplexes without compromising the efficiency of RNAi. These results suggest that inhibition of gene expression by RNAi is compatible with a broad spectrum of chemical modifications to the duplex, affording a wide range of useful options for probing the mechanism of RNAi and for improving RNA interference in vivo.
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Cites
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Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate
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Specific interference with gene function by double-stranded RNA in early mouse development
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Locked nucleic acid (LNA): fine-tuning the recognition of DNA and RNA
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Self-citationNucleic-acid therapeutics: basic principles and recent applications
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Evidence that siRNAs Function as Guides, Not Primers, in the Drosophila and Human RNAi Pathways
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Cited by
Illuminating the silence: understanding the structure and function of small RNAs
Rana, T. M. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2085 · Cited by 1,083
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
siRNAs: applications in functional genomics and potential as therapeutics
Dorsett, Y., & Tuschl, T. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1345 · Cited by 909
LNA (Locked Nucleic Acid): High-Affinity Targeting of Complementary RNA and DNA
Vester, B., & Wengel, J. (2004) · Biochemistry · doi:10.1021/bi0485732 · Cited by 727
Progress towards in Vivo Use of siRNAs
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Metadata
- Authors
- Braasch, D. A., Jensen, S., Liu, Y., Kaur, K., Arar, K., White, M. A., & Corey, D. R.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-06-11
- Volume
- 42
- Issue
- 26
- Pages
- 7967-7975
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W1994983564
- Cited by
- 531
- References
- 11
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- closed
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- Braasch, D. A., Jensen, S., Liu, Y., Kaur, K., Arar, K., White, M. A., & Corey, D. R. (2003). RNA Interference in Mammalian Cells by Chemically-Modified RNA. Biochemistry. https://doi.org/10.1021/bi0343774
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