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Tunable Target Degradation Platform

TTDschem

Transformational Target Validation through Tunable Degradation

EnBiotix’s novel and proprietary Tunable Target Degradation (TTD) platform allows for unprecedented experimental target validation, and represents a significant advance over genetic-knockouts(limited utility in studying essential genes due to their binary outcome) or anti-sense silencing (effects on distal gene expression).

TTD enables validation of essential as well as non-essential targets, and only modifies functions directly affected by the target protein.  Based on a 2014 Collins publication in Nature Biotechnology, the inducible protease TTD platform:

  • Yields functional assessments of targets, pathways, MOAs in vitro and in vivo
  • Determines the level of inhibition required to achieve a desired phenotype
  • Assesses target vulnerability without a chemical inhibitor

Key developments:

  • A library of TTD-modified coli essential genes has been constructed and characterized
  • Library can be used to identify highest value candidate targets for novel anti-infectives
  • Broadly applicable to other bacterial species and strains

Bacterial strains with TTD-modified proteins show proof-of-concept of hypersensitivity to antibiotic treatment. Proof-of-concept also demonstrated using TTD for precise control of steady-state levels of a target to determine the phenotype associated with that level of target inhibition