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Applications and considerations for the use of genetically engineered mouse models in drug development

  • Joshua D. WebsterEmail author
  • Sara F. Santagostino
  • Oded Foreman
Review
  • 73 Downloads

Abstract

Considering high drug attrition rates in clinical studies and the overall complexity and challenging environment of drug development, it is increasingly important to understand the therapeutic molecule and target and how they intersect with disease biology as fully as possible. This requires one to use numerous tools and investigative approaches in combination. Genetically engineered mouse models are a critical component to the drug development toolbox as they can provide key insights across multiple steps of the drug development process. While knock-out and knock-in mice can inform questions of basic biology, genetically engineered mice can also be applied to model diseases for efficacy studies, to discriminate on-target and off-target effects of novel therapeutics, and to inform an array of biologic and pharmacologic questions, including pharmacodynamics, pharmacokinetics, and biomarker discovery. However, use of these models requires not only an understanding of their strengths and limitations but also a careful consideration of the context in which they are being used and the hypotheses being addressed by them. Additionally, they should not be used in isolation, but instead in combination with other biochemical, in vitro, and clinical data to create a broad understanding of the drug, target, and disease biology.

Keywords

Genetically engineered mouse models GEMM Drug development Knock-out mice Drug safety 

Notes

Compliance with ethical standards

Conflict of interest

All the authors are employees of Genentech and, as such, stockholders in Roche. The authors have no other conflicts of interest or funding sources to report.

Human and animal rights and informed consent

As a review article, this paper does not contain any original studies with human participants or animals performed by any of the authors. Some referenced published data includes animal studies performed by the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed in this study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Joshua D. Webster
    • 1
    Email author
  • Sara F. Santagostino
    • 2
  • Oded Foreman
    • 1
  1. 1.Research PathologyGenentechSouth San FranciscoUSA
  2. 2.Safety Assessment PathologyGenentechSouth San FranciscoUSA

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