Synthetic Dicer-Substrate siRNAs as Triggers of RNA Interference View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2013

AUTHORS

Scott D. Rose , Mark A. Behlke

ABSTRACT

The first synthetic oligonucleotides used to suppress gene expression in mammalian cells via RNA interference were 21-nucleotide (nt) RNA duplexes having symmetric 2-nt 3′-overhangs and were designed to mimic the natural products of Dicer processing of long RNA substrates. Synthetic RNA duplexes which are longer than 23-nt length are substrates for processing by Dicer and can show increased potency as artificial triggers of RNA interference, particularly at a low concentration. Longer duplexes, however, can have variable cleavage patterns following Dicer processing which can adversely affect potency. Optimized synthetic Dicer substrates are asymmetric duplexes having a 25-nt passenger strand and a 27-nt guide strand with a single 2-nt 3′-overhang on the guide strand and modified bases at the 3′-end of the passenger strand. This modified design results in predictable patterns of Dicer processing and shows improved activity. The development of this design strategy and use of Dicer-substrate RNAs to trigger gene suppression in a variety of systems will be reviewed in this chapter. More... »

PAGES

31-56

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  • Book

    TITLE

    RNA Interference from Biology to Therapeutics

    ISBN

    978-1-4614-4743-6
    978-1-4614-4744-3

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/978-1-4614-4744-3_2

    DOI

    http://dx.doi.org/10.1007/978-1-4614-4744-3_2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1028622855


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