Chan Anthony W S
ILAR J. 2013;54(2):211-23. doi: 10.1093/ilar/ilt035.
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.
利用基因改造(转基因)非人灵长类动物(NHPs)来模拟人类疾病的兴趣日益浓厚,这是因为NHPs(恒河猴等)与人类关系密切。NHPs在解剖学、生理学、遗传学和神经功能方面,以及在认知、情感和社会行为方面,与人类有着相似的发育路径。生物医学研究中的NHP模型在疫苗开发、辅助生殖技术以及许多疾病的新疗法研发中发挥了重要作用。生物医学研究并非NHPs的主要作用。它们主要用于安全性评估和药代动力学研究,而非确定治疗效果。首例转基因恒河猴的诞生(2001年)彻底改变了NHP模型在生物医学中的作用。亨廷顿舞蹈病转基因NHP模型的开发(2008年)具有独特的临床特征,进一步表明了该模型系统的独特性,以及NHP模型在人类遗传疾病研究中的潜在作用。由于分子、基因和胚胎技术的最新进展,利用NHPs模拟人类遗传疾病的研究将持续蓬勃发展。NHPs在生物医学研究,特别是临床前研究中日益重要的作用是可以预见的。需要审视转基因NHPs的发展路径及其在未来生物医学新角色中的前景。本文将聚焦过去十年转基因NHPs的进展,包括转基因技术和疾病建模。将概述可能对未来NHP建模产生重大影响的新技术,并以对转基因NHP模型未来前景的讨论作为结尾。