Engineering Xenopus embryos for phenotypic drug discovery screening

Adv Drug Deliv Rev. 2014 Apr:69-70:225-46. doi: 10.1016/j.addr.2014.02.004. Epub 2014 Feb 24.


Many rare human inherited diseases remain untreatable despite the fact that the disease causing genes are known and adequate mouse disease models have been developed. In vivo phenotypic drug screening relies on isolating drug candidates by their ability to produce a desired therapeutic phenotype in whole organisms. Embryos of zebrafish and Xenopus frogs are abundant, small and free-living. They can be easily arrayed in multi-well dishes and treated with small organic molecules. With the development of novel genome modification tools, such a zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas, it is now possible to efficiently engineer non-mammalian models of inherited human diseases. Here, we will review the rapid progress made in adapting these novel genome editing tools to Xenopus. The advantages of Xenopus embryos as in vivo models to study human inherited diseases will be presented and their utility for drug discovery screening will be discussed. Being a tetrapod, Xenopus complements zebrafish as an indispensable non-mammalian animal model for the study of human disease pathologies and the discovery of novel therapeutics for inherited diseases.

Keywords: CRISPR/Cas; Genome editing; Human disease models; Morpholinos; TALENs; Transgenesis; Xenopus laevis; Xenopus tropicalis; Zebrafish; Zinc-finger nucleases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Discovery / methods*
  • Drug Discovery / trends
  • Drug Evaluation, Preclinical / methods
  • Drug Evaluation, Preclinical / trends
  • Genetic Engineering / methods*
  • Genetic Engineering / trends
  • Humans
  • Life Cycle Stages / physiology
  • Phenotype*
  • Xenopus / embryology*