Prediction of antisense oligonucleotide binding affinity to a structured RNA target

S. Patrick Walton, Gregory N. Stephanopoulos, Martin L. Yarmush, Charles M. Roth

Research output: Contribution to journalArticle

  • 39 Citations

Abstract

Antisense oligonucleotides, which act through the pairing of complementary bases to an RNA target sequence, are showing great promise in research and clinical applications. However, the selection of effective antisense oligonucleotides has proven more difficult than initially presumed. We developed a prediction algorithm to identify those sequences with the highest predicted binding affinity for their target mRNA based on a thermodynamic cycle that accounts for the energetics of structural alterations in both the target mRNA and the oligonucleotide. The model was used to predict the binding affinity of antisense oligonucleotides complementary to the rabbit β-globin (RBG) and mouse tumor necrosis factor- α (TNFα) mRNAs, for which large experimental datasets were available. Of the top ten candidates identified by the algorithm for the RBG mRNA, six were the most strongly binding sequences determined from an experimental assay. The prediction for the TNFα mRNA also identified high affinity sequences with ~60% accuracy. Computational prediction of antisense efficacy is more cost-efficient and faster than in vitro or in vivo selection and can potentially speed the development of sequences for both research and clinical applications.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalBiotechnology and Bioengineering
Volume65
Issue number1
DOIs
StatePublished - Oct 5 1999
Externally publishedYes

Profile

Antisense Oligonucleotides
RNA
Messenger RNA
Oligonucleotides
beta-Globins
Tumor Necrosis Factor-alpha
Rabbits
Caprylates
Airway Obstruction
Thermodynamics
Base Pairing
Costs and Cost Analysis
Datasets
In Vitro Techniques
Assays
Costs
Flupenthixol
Anthralin
Beryllium
Alkynes

Keywords

  • Affinity
  • Antisense
  • Hybridization
  • RNA folding

ASJC Scopus subject areas

  • Biotechnology
  • Microbiology

Cite this

Prediction of antisense oligonucleotide binding affinity to a structured RNA target. / Walton, S. Patrick; Stephanopoulos, Gregory N.; Yarmush, Martin L.; Roth, Charles M.

In: Biotechnology and Bioengineering, Vol. 65, No. 1, 05.10.1999, p. 1-9.

Research output: Contribution to journalArticle

Walton, S. Patrick; Stephanopoulos, Gregory N.; Yarmush, Martin L.; Roth, Charles M. / Prediction of antisense oligonucleotide binding affinity to a structured RNA target.

In: Biotechnology and Bioengineering, Vol. 65, No. 1, 05.10.1999, p. 1-9.

Research output: Contribution to journalArticle

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