Hunter Jacqueline E, Molony Caitlyn M, Bagel Jessica H, O'Donnell Patricia A, Kaler Stephen G, Wolfe John H
Research Institute of Children's Hospital of Philadelphia, 502-G Abramson Research Center, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Ther Methods Clin Dev. 2022 Jul 16;26:384-393. doi: 10.1016/j.omtm.2022.07.007. eCollection 2022 Sep 8.
Multiple studies have examined the transduction characteristics of different AAV serotypes in the mouse brain, where they can exhibit significantly different patterns of transduction. The pattern of transduction also varies with the route of administration. Much less information exists for the transduction characteristics in large-brained animals. Large animal models have brains that are closer in size and organization to the human brain, such as being gyrencephalic compared to the lissencephalic rodent brains, pathway organization, and certain electrophysiologic properties. Large animal models are used as translational intermediates to develop gene therapies to treat human diseases. Various AAV serotypes and routes of delivery have been used to study the correction of pathology in the brain in lysosomal storage diseases. In this study, we evaluated the ability of selected AAV serotypes to transduce cells in the cat brain when delivered into the cerebrospinal fluid via the . We previously showed that AAV1 transduced significantly greater numbers of cells than AAV9 in the cat brain by this route. In the present study, we evaluated serotypes closely related to AAVs 1 and 9 (AAVs 6, AS, hu32) that may mediate more extensive transduction, as well as AAVs 4 and 5, which primarily transduce choroid plexus epithelial (CPE) and ependymal lining cells in the rodent brain. The related serotypes tended to have similar patterns of transduction but were divergent in some specific brain structures.
多项研究已考察了不同腺相关病毒（AAV）血清型在小鼠大脑中的转导特性，在小鼠大脑中它们可呈现出显著不同的转导模式。转导模式也会因给药途径而异。关于大脑较大动物的转导特性的信息则少得多。大型动物模型的大脑在大小和组织结构上更接近人类大脑，例如与无脑回的啮齿动物大脑相比，其大脑有脑回，有通路组织以及某些电生理特性。大型动物模型被用作转化中间体来开发治疗人类疾病的基因疗法。已使用各种AAV血清型和递送途径来研究溶酶体贮积病中大脑病理的纠正。在本研究中，我们评估了选定的AAV血清型经[具体途径]注入脑脊液后在猫脑中转导细胞的能力。我们之前表明，通过该途径，AAV1在猫脑中转导的细胞数量明显多于AAV9。在本研究中，我们评估了与AAV1和AAV9密切相关的血清型（AAV6、AS、hu32），它们可能介导更广泛的转导，以及AAV4和AAV5，它们主要在啮齿动物大脑中转导脉络丛上皮（CPE）细胞和室管膜衬里细胞。相关血清型往往具有相似的转导模式，但在某些特定脑结构中存在差异。
