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提高非人灵长类动物颅内病毒载体递送的疗效和可及性。

Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates.

作者信息

Griggs Devon J, Garcia Aaron D, Au Wing Yun, Ojemann William K S, Johnson Andrew Graham, Ting Jonathan T, Buffalo Elizabeth A, Yazdan-Shahmorad Azadeh

机构信息

Department of Electrical and Computer Engineering, University of Washington, Seattle, WA 98195, USA.

Washington National Primate Research Center, Seattle, WA 98195, USA.

出版信息

Pharmaceutics. 2022 Jul 8;14(7):1435. doi: 10.3390/pharmaceutics14071435.

Abstract

Non-human primates (NHPs) are precious resources for cutting-edge neuroscientific research, including large-scale viral vector-based experimentation such as optogenetics. We propose to improve surgical outcomes by enhancing the surgical preparation practices of convection-enhanced delivery (CED), which is an efficient viral vector infusion technique for large brains such as NHPs'. Here, we present both real-time and next-day MRI data of CED in the brains of ten NHPs, and we present a quantitative, inexpensive, and practical bench-side model of the in vivo CED data. Our bench-side model is composed of food coloring infused into a transparent agar phantom, and the spread of infusion is optically monitored over time. Our proposed method approximates CED infusions into the cortex, thalamus, medial temporal lobe, and caudate nucleus of NHPs, confirmed by MRI data acquired with either gadolinium-based or manganese-based contrast agents co-infused with optogenetic viral vectors. These methods and data serve to guide researchers and surgical team members in key surgical preparations for intracranial viral delivery using CED in NHPs, and thus improve expression targeting and efficacy and, as a result, reduce surgical risks.

摘要

非人灵长类动物(NHPs)是前沿神经科学研究的宝贵资源,包括基于大规模病毒载体的实验,如光遗传学。我们建议通过改进对流增强递送(CED)的手术准备操作来提高手术效果,CED是一种用于如NHPs大脑等大型大脑的高效病毒载体注入技术。在此,我们展示了十只NHPs大脑中CED的实时和次日MRI数据,并展示了一种定量、廉价且实用的体内CED数据的台式模型。我们的台式模型由注入透明琼脂模型中的食用色素组成,并随时间对注入的扩散进行光学监测。我们提出的方法近似于向NHPs的皮质、丘脑、内侧颞叶和尾状核进行CED注入,这通过与光遗传学病毒载体共同注入的基于钆或基于锰的造影剂获取的MRI数据得到证实。这些方法和数据有助于指导研究人员和手术团队成员进行关键的手术准备,以便在NHPs中使用CED进行颅内病毒递送,从而改善表达靶向性和疗效,并因此降低手术风险。

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