Integrating molecular thermodynamics and systems biology to improve the cellular effectiveness of antisense oligonucleotides

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Antisense oligonucleotides (AS ONs) are a powerful means to inhibit the expression of specific genes, but their effectiveness is limited by factors including cellular delivery, biochemical attack, and poor binding to target. We have developed a systems model of the processes required for an antisense oligonucleotide to be successfully delivered and to exert activity in a cell. The model demonstrates a sensitive dependence of the extent of gene expression inhibition on the binding rate for the ON-mRNA interaction. We have focused on the binding event and developed a molecular thermodynamic model based on ON and mRNA folding that predicts accurately the affinity of ON-mRNA binding, and we have observed experimentally that affinity correlates directly with binding rate for these species. Most importantly, we have found that the model successfully selects those ONs that are most successful in cell culture. Taken together, these tools may help accelerate the development of this promising technology.

Original languageEnglish (US)
Title of host publicationProceedings of the IEEE 29th Annual Northeast Bioengineering Conference
EditorsStanley Reisman, Richard Foulds, Bruno Mantilla
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages162-163
Number of pages2
ISBN (Electronic)0780377672
DOIs
StatePublished - 2003
Event29th IEEE Annual Northeast Bioengineering Conference, NEBC 2003 - Newark, United States
Duration: Mar 22 2003Mar 23 2003

Publication series

NameProceedings of the IEEE Annual Northeast Bioengineering Conference, NEBEC
Volume2003-January

Other

Other29th IEEE Annual Northeast Bioengineering Conference, NEBC 2003
Country/TerritoryUnited States
CityNewark
Period3/22/033/23/03

All Science Journal Classification (ASJC) codes

  • Bioengineering

Keywords

  • Biomedical engineering
  • Cells (biology)
  • Chemical engineering
  • Equations
  • Gene expression
  • Power engineering and energy
  • Predictive models
  • Sequences
  • Systems biology
  • Thermodynamics

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