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

Guoping Feng, Frances E. Jensen, Henry T. Greely, Hideyuki Okano, Stefan Treue, Angela C. Roberts, James G. Fox, Sarah Caddick, Mu Ming Poo, William T. Newsome, John H. Morrison

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)24022-24031
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number39
DOIs
StatePublished - Sep 29 2020

Keywords

  • CRISPR
  • Disease models
  • Genetic engineering
  • Nonhuman primate
  • Primates

ASJC Scopus subject areas

  • General

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