Advances in AAV technology for delivering genetically encoded cargo to the nonhuman primate nervous system

Lillian J. Campos , Cynthia M. Arokiaraj , Miguel R. Chuapoco , Xinhong Chen , Nick Goeden , Viviana Gradinaru , Andrew S. Fox
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引用次数: 3

Abstract

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.

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向非人灵长类动物神经系统递送基因编码货物的AAV技术进展
现代神经科学方法,包括光遗传学、钙成像和其他遗传操作,促进了我们解剖啮齿动物模型中特定电路以研究其在神经疾病中的作用的能力。这些方法经常使用病毒载体将基因货物(如视蛋白)输送到特定组织和基因工程啮齿动物,以实现细胞类型特异性。然而,由于缺乏有效的灵长类病毒载体,这些啮齿动物模型的可翻译性、已确定靶点的跨物种验证以及潜在治疗方法在非人灵长类等大型动物模型中的翻译效力仍然很困难。对非人灵长类神经系统的深入了解有望为神经和神经退行性疾病的治疗提供指导。在此,我们概述了腺相关病毒载体在非人灵长类动物中优化使用的最新进展。这些工具有望为转化神经科学的研究开辟新的途径,并进一步加深我们对灵长类动物大脑的理解。
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