Campos Lillian J, Arokiaraj Cynthia M, Chuapoco Miguel R, Chen Xinhong, Goeden Nick, Gradinaru Viviana, Fox Andrew S
Department of Psychology and the California National Primate Research Center, University of California, Davis, CA, 05616, USA.
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
Curr Res Neurobiol. 2023 Apr 7;4:100086. doi: 10.1016/j.crneur.2023.100086. eCollection 2023.
Modern neuroscience approaches including optogenetics, calcium imaging, and other genetic manipulations have facilitated our ability to dissect specific circuits in rodent models to study their role in neurological disease. These approaches regularly use viral vectors to deliver genetic cargo (e.g., opsins) to specific tissues and genetically-engineered rodents to achieve cell-type specificity. However, the translatability of these rodent models, cross-species validation of identified targets, and translational efficacy of potential therapeutics in larger animal models like nonhuman primates remains difficult due to the lack of efficient primate viral vectors. A refined understanding of the nonhuman primate nervous system promises to deliver insights that can guide the development of treatments for neurological and neurodegenerative diseases. Here, we outline recent advances in the development of adeno-associated viral vectors for optimized use in nonhuman primates. These tools promise to help open new avenues for study in translational neuroscience and further our understanding of the primate brain.
包括光遗传学、钙成像和其他基因操作在内的现代神经科学方法,提升了我们在啮齿动物模型中剖析特定神经回路以研究其在神经疾病中作用的能力。这些方法通常使用病毒载体将基因物质(如视蛋白)递送至特定组织,并利用基因工程啮齿动物来实现细胞类型特异性。然而,由于缺乏高效的灵长类病毒载体,这些啮齿动物模型的可转化性、已鉴定靶点的跨物种验证以及潜在疗法在非人类灵长类等大型动物模型中的转化效果仍然困难重重。对非人类灵长类神经系统的深入理解有望提供洞见,以指导神经和神经退行性疾病治疗方法的开发。在此,我们概述了腺相关病毒载体开发方面的最新进展,这些载体旨在优化用于非人类灵长类动物。这些工具有望为转化神经科学研究开辟新途径,并加深我们对灵长类大脑的理解。