Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research

Proc Natl Acad Sci U S A. 2020 Sep 29;117(39):24022-24031. doi: 10.1073/pnas.2006515117. Epub 2020 Aug 19.


The recently developed new genome-editing technologies, such as the CRISPR/Cas system, have opened the door for generating genetically modified nonhuman primate (NHP) models for basic neuroscience and brain disorders research. The complex circuit formation and experience-dependent refinement of the human brain are very difficult to model in vitro, and thus require use of in vivo whole-animal models. For many neurodevelopmental and psychiatric disorders, abnormal circuit formation and refinement might be at the center of their pathophysiology. Importantly, many of the critical circuits and regional cell populations implicated in higher human cognitive function and in many psychiatric disorders are not present in lower mammalian brains, while these analogous areas are replicated in NHP brains. Indeed, neuropsychiatric disorders represent a tremendous health and economic burden globally. The emerging field of genetically modified NHP models has the potential to transform our study of higher brain function and dramatically facilitate the development of effective treatment for human brain disorders. In this paper, we discuss the importance of developing such models, the infrastructure and training needed to maximize the impact of such models, and ethical standards required for using these models.

Keywords: CRISPR; disease models; genetic engineering; nonhuman primate; primates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animal Experimentation / ethics*
  • Animals
  • Disease Models, Animal*
  • Mental Disorders / genetics*
  • Mental Disorders / physiopathology
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / physiopathology
  • Neurosciences / ethics
  • Neurosciences / methods
  • Primates / genetics*
  • Primates / physiology