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Drug target validation: Lethal infection blocked by inducible peptide

Authors
  • Jianshi Tao
  • Philip Wendler
  • Gene Connelly
  • Audrey Lim
  • Jiansu Zhang
  • Megan King
  • Tongchuan Li
  • Jared A. Silverman
  • Paul R. Schimmel
  • Francis P. Tally
Publisher
The National Academy of Sciences
Publication Date
Jan 18, 2000
Source
PMC
Keywords
License
Unknown

Abstract

Genome projects are generating large numbers of potential new targets for drug discovery. One challenge is target validation, proving the usefulness of a specific target in an animal model. In this paper, we demonstrate a new approach to validation and assay development. We selected in vitro specific peptide binders to a potential pathogen target. By inducing the expression of a selected peptide in pathogen cells causing a lethal infection in mice, the animals were rescued. Thus, by combining in vitro selection methods for peptide binders with inducible expression in animals, the target's validity was rigorously tested and demonstrated. This approach to validation can be generalized and has the potential to become a valuable tool in the drug discovery process.

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