Selection of antisense oligonucleotides based on multiple predicted target mRNA structures

BMC Bioinformatics
Xiaochen BoShengqi Wang

Abstract

Local structures of target mRNAs play a significant role in determining the efficacies of antisense oligonucleotides (ODNs), but some structure-based target site selection methods are limited by uncertainties in RNA secondary structure prediction. If all the predicted structures of a given mRNA within a certain energy limit could be used simultaneously, target site selection would obviously be improved in both reliability and efficiency. In this study, some key problems in ODN target selection on the basis of multiple predicted target mRNA structures are systematically discussed. Two methods were considered for merging topologically different RNA structures into integrated representations. Several parameters were derived to characterize local target site structures. Statistical analysis on a dataset with 448 ODNs against 28 different mRNAs revealed 9 features quantitatively associated with efficacy. Features of structural consistency seemed to be more highly correlated with efficacy than indices of the proportion of bases in single-stranded or double-stranded regions. The local structures of the target site 5' and 3' termini were also shown to be important in target selection. Neural network efficacy predictors using these feat...Continue Reading

References

Jan 11, 1982·Nucleic Acids Research·J P Dumas, J Ninio
Jan 11, 1984·Nucleic Acids Research·K YamamotoH Yoshikura
Feb 15, 1993·Biochemical and Biophysical Research Communications·A R ThierryA Dritschilo
Jun 1, 1997·Nature Biotechnology·N MilnerE M Southern
Jan 1, 1997·Methods in Molecular Biology·W James, E Cowe
May 21, 1998·Antisense & Nucleic Acid Drug Development·S T Crooke
Dec 16, 1998·Nature Biotechnology·O MatveevaS M Freier
Jul 15, 1999·Computers & Chemistry·Y Ding, C E Lawrence
Feb 24, 2000·Nucleic Acids Research·T A VickersS M Freier
Jul 13, 2000·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·M FeketeP F Stadler
Oct 18, 2000·Advanced Drug Delivery Reviews·M Sohail, E M Southern
Feb 24, 2001·Quarterly Reviews of Biophysics·P G Higgs
Oct 24, 2001·Current Opinion in Oncology·K T FlahertyP J O'Dwyer
Oct 5, 2002·Nucleic Acids Research·Michael C GiddingsOlga V Matveeva
Dec 20, 2002·Bioinformatics·Alistair M Chalk, Erik L L Sonnhammer
Jun 26, 2003·Nucleic Acids Research·Michael Zuker
Jun 26, 2003·Nucleic Acids Research·Ivo L Hofacker
Aug 22, 2003·Nucleic Acids Research·O V MatveevaS M Freier
Dec 4, 2003·Nature Biotechnology·Lisa J Scherer, John J Rossi
Jun 25, 2004·Nucleic Acids Research·Ye DingCharles E Lawrence
Sep 24, 2004·BMC Bioinformatics·Gustavo Camps-VallsErik L L Sonnhammer
Dec 31, 2005·Nucleic Acids Research·Xiaochen BoShengqi Wang
Jan 1, 1994·IEEE Transactions on Neural Networks·M T Hagan, M B Menhaj

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Methods Mentioned

BETA
gene knockout

Software Mentioned

SSPP
SFold
Matlab Neural Network Toolbox
MFold
Vienna
SUP
MathType

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