siSPOTR: a tool for designing highly specific and potent siRNAs for human and mouse

Ryan L Boudreau; Ryan M Spengler; Ray H Hylock; Brandyn J Kusenda; Heather A Davis; David A Eichmann; Beverly L Davidson

doi:10.1093/nar/gks797

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siSPOTR: a tool for designing highly specific and potent siRNAs for human and mouse

Journal article

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siSPOTR: a tool for designing highly specific and potent siRNAs for human and mouse

Ryan L Boudreau, Ryan M Spengler, Ray H Hylock, Brandyn J Kusenda, Heather A Davis, David A Eichmann and Beverly L Davidson

Nucleic acids research, Vol.41(1), pp.e9-e9

01/2013

DOI: 10.1093/nar/gks797

PMCID: PMC3592398

PMID: 22941647

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Abstract

RNA interference (RNAi) serves as a powerful and widely used gene silencing tool for basic biological research and is being developed as a therapeutic avenue to suppress disease-causing genes. However, the specificity and safety of RNAi strategies remains under scrutiny because small inhibitory RNAs (siRNAs) induce off-target silencing. Currently, the tools available for designing siRNAs are biased toward efficacy as opposed to specificity. Prior work from our laboratory and others’ supports the potential to design highly specific siRNAs by limiting the promiscuity of their seed sequences (positions 2–8 of the small RNA), the primary determinant of off-targeting. Here, a bioinformatic approach to predict off-targeting potentials was established using publically available siRNA data from more than 50 microarray experiments. With this, we developed a specificity-focused siRNA design algorithm and accompanying online tool which, upon validation, identifies candidate sequences with minimal off-targeting potentials and potent silencing capacities. This tool offers researchers unique functionality and output compared with currently available siRNA design programs. Furthermore, this approach can greatly improve genome-wide RNAi libraries and, most notably, provides the only broadly applicable means to limit off-targeting from RNAi expression vectors.

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Title: Subtitle: siSPOTR: a tool for designing highly specific and potent siRNAs for human and mouse
Creators: Ryan L Boudreau - Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
Ryan M Spengler - Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
Ray H Hylock - Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
Brandyn J Kusenda - Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
Heather A Davis - Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
David A Eichmann - Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
Beverly L Davidson - Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.41(1), pp.e9-e9
DOI: 10.1093/nar/gks797
PMID: 22941647
PMCID: PMC3592398
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Publisher: Oxford University Press
Language: English
Date published: 01/2013
Academic Unit: School of Library and Information Science; Internal Medicine
Record Identifier: 9984003004802771

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