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PMID: 1352874 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Predicting antisense oligonucleotide inhibitory efficacy: a computational approach using histograms and thermodynamic indices.

Nucleic acids research ·Vol. 20 ·No. 13 ·1992-07-11 ·Pages 3501-8

Stull RA, Taylor LA, Szoka FC

Abstract

Antisense oligonucleotides (ASOs) are designed to bind to a specific mRNA and selectively suppress its translation. To facilitate selection of optimal ASO targets, we have developed three thermodynamic indices to evaluate putative structural complexes important in ASO action. These indices are: a secondary structure score (Sscore), which estimates the strength of local mRNA secondary structures at the ASO target site; a duplex score (Dscore), which estimates the delta Gformation for the ASO:mRNA target sequence duplex; and a competition score (Cscore), which is the difference between the Dscore and the Sscore. We also present two histograms to graphically display these indices from different regions of the mRNA. The indices are compared to the inhibition reported in five studies of ASO-mediated suppression of gene expression. The Dscore is the most consistent predictor of ASO efficacy in four of the five studies (r2 from 0.44 to 0.99), while the results of the fifth study could not be predicted by any thermodynamic or physical index. Thus the Dscores and their histogram may prove useful in selection of ASO targets.

Related Genes
DHFR ICAM-1 c-myc
MeSH Terms
Algorithms Base Sequence Cell Adhesion Molecules/genetics Cell Line Genes, myc/genetics Globins/genetics Humans Intercellular Adhesion Molecule-1 Molecular Sequence Data Monte Carlo Method Nucleic Acid Conformation Oligonucleotides, Antisense/genetics,metabolism RNA, Messenger/genetics,metabolism Temperature Tetrahydrofolate Dehydrogenase/genetics
Chemicals
Cell Adhesion Molecules Oligonucleotides, Antisense RNA, Messenger Intercellular Adhesion Molecule-1 Globins Tetrahydrofolate Dehydrogenase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Stull R A
Department of Pharmacy, University of California, San Francisco 94143-0446.
Taylor L A
Szoka F C
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/20.13.3501
Published
1992-07-11
Pages
3501-8
Language
English
Region
England
NLM ID
0411011
PMCID
PMC312508
Subset
IM
Grants
NIGMS NIH HHS · GM 30163 · United States
Databases
GENBANK
J00120, J00659, M24283, X00855
External Links
PubMed source DOI: 10.1093/nar/20.13.3501 PMC Full Text View journal details
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