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Translational Safety Genetics - Leveraging Genetic Variation for Enhanced Safety Assessment

Bhoumik, Priyasma and Del Rio Espinola, Alberto and Hahne, Florian and Moggs, Jonathan and Grenet, Olivier (2016) Translational Safety Genetics - Leveraging Genetic Variation for Enhanced Safety Assessment. Experimental and Toxicologic Pathology. ISSN 0192-62331533-1601

Abstract

The emerging field of translational safety genetics is providing new opportunities to
enhance drug discovery and development. Genetic variation in therapeutic drug targets,
off-target interactors, and relevant drug metabolism/disposition pathways can contribute
to diverse drug pharmacologic and toxicologic responses between different animal
species, strains and geographic origins. Recent advances in the sequencing of rodent,
canine, non-human primate, and minipig genomes have dramatically improved the
ability to select the most appropriate animal species for preclinical drug toxicity studies
based on genotypic characterization of drug targets/pathways and drug metabolism
and/or disposition, thus avoiding inconclusive or misleading animal studies, consistent
with the principles of the 3Rs (Replacement, Reduction and Refinement). The genetic
background of individual animals should also be taken into consideration when
interpreting phenotypic outcomes from toxicity studies & susceptibilities to spontaneous
safety-relevant background findings.

Item Type: Article
Date Deposited: 10 Dec 2016 00:45
Last Modified: 10 Dec 2016 00:45
URI: https://oak.novartis.com/id/eprint/30988

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