Progress and prospects for genetic modification of nonhuman primate models in biomedical research

Abstract

The growing interest of modeling human diseases using genetically modified (transgenic) nonhuman primates (NHPs) is a direct result of NHPs (rhesus macaque, etc.) close relation to humans. NHPs share similar developmental paths with humans in their anatomy, physiology, genetics, and neural functions; and in their cognition, emotion, and social behavior. The NHP model within biomedical research has played an important role in the development of vaccines, assisted reproductive technologies, and new therapies for many diseases. Biomedical research has not been the primary role of NHPs. They have mainly been used for safety evaluation and pharmacokinetics studies, rather than determining therapeutic efficacy. The development of the first transgenic rhesus macaque (2001) revolutionized the role of NHP models in biomedicine. Development of the transgenic NHP model of Huntington's disease (2008), with distinctive clinical features, further suggested the uniqueness of the model system; and the potential role of the NHP model for human genetic disorders. Modeling human genetic diseases using NHPs will continue to thrive because of the latest advances in molecular, genetic, and embryo technologies. NHPs rising role in biomedical research, specifically pre-clinical studies, is foreseeable. The path toward the development of transgenic NHPs and the prospect of transgenic NHPs in their new role in future biomedicine needs to be reviewed. This article will focus on the advancement of transgenic NHPs in the past decade, including transgenic technologies and disease modeling. It will outline new technologies that may have significant impact in future NHP modeling and will conclude with a discussion of the future prospects of the transgenic NHP model.

Keywords: animal model; human diseases; nonhuman primates; transgenesis.