Chemical modification: the key to clinical application of RNA interference?
David R. Corey
David R. Corey
Published December 3, 2007
Citation Information: J Clin Invest. 2007;117(12):3615-3622. https://doi.org/10.1172/JCI33483.
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Review Series

Chemical modification: the key to clinical application of RNA interference?

Abstract

RNA interference provides a potent and specific method for controlling gene expression in human cells. To translate this potential into a broad new family of therapeutics, it is necessary to optimize the efficacy of the RNA-based drugs. As discussed in this Review, it might be possible to achieve this optimization using chemical modifications that improve their in vivo stability, cellular delivery, biodistribution, pharmacokinetics, potency, and specificity.

Authors

David R. Corey

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Figure 1

(A) siRNAs are double-stranded RNAs approximately 20 base-pairs in length.

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(A) siRNAs are double-stranded RNAs approximately 20 base-pairs in lengt...
The duplex shown has staggered ends capped with two thymidines to improve resistance to digestion by nucleases. This is a traditional design, but it is possible to have blunt-ended duplexes, and the thymidines can be omitted. (B) Duplex siRNAs enter cells and bind to the RISC. The RISC proteins unravel the duplex and facilitate the search for mRNA sequences that are complementary to one of the RNA strands. Upon recognition of a complementary mRNA, RISC cleaves the mRNA and prevents translation.