Arotcarena Marie-Laure, Dovero Sandra, Biendon Nathalie, Dutheil Nathalie, Planche Vincent, Bezard Erwan, Dehay Benjamin
CNRS, IMN, UMR 5293, Univ. Bordeaux, Bordeaux, France.
Centre Memoire de Ressources et de Recherches, Pôle de Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France.
Front Bioeng Biotechnol. 2021 Nov 15;9:762209. doi: 10.3389/fbioe.2021.762209. eCollection 2021.
Adeno-associated virus (AAV) vectors are increasingly used as an effective and safe approach to deliver genetic material to the central nervous system (CNS). The AAV9-derived variants, AAV-PHP. B and AAV-PHP.eB, reportedly broadly transduce cells throughout the CNS compared to the original serotype 9, AAV9. As non-human primate data are scarce, we here evaluated the CNS transduction efficiencies after lumbar intrathecal bolus delivery of identical doses of either AAV-PHP. B:CAG-EGFP or AAV-PHP. eB:CAG-EGFP in rhesus macaque monkeys. AAV-PHP.eB achieved a more efficient and widespread CNS transduction compared to AAV-PHP.B. We report a strong neuronal and oligodendroglial tropism for both variants in the putamen and in the hippocampus. This proof-of-concept experiment highlights the potential value of intrathecal infusions of AAV-PHP.eB to distribute genetic material in the CNS with cell-type specificity and introduces a new opportunity to model brain diseases in rhesus macaque monkeys and further develop gene therapies targeting the CNS in humans.
腺相关病毒（AAV）载体越来越多地被用作一种有效且安全的方法，将遗传物质递送至中枢神经系统（CNS）。据报道，与原始血清型9（AAV9）相比，源自AAV9的变体AAV-PHP.B和AAV-PHP.eB能广泛转导整个中枢神经系统的细胞。由于非人类灵长类动物的数据稀缺，我们在此评估了在恒河猴中经腰椎鞘内推注相同剂量的AAV-PHP.B:CAG-EGFP或AAV-PHP.eB:CAG-EGFP后中枢神经系统的转导效率。与AAV-PHP.B相比，AAV-PHP.eB实现了更高效、更广泛的中枢神经系统转导。我们报告了这两种变体在壳核和海马体中对神经元和少突胶质细胞具有强烈的嗜性。这个概念验证实验突出了鞘内注射AAV-PHP.eB在中枢神经系统中以细胞类型特异性方式分布遗传物质的潜在价值，并为在恒河猴中模拟脑部疾病以及进一步开发针对人类中枢神经系统的基因疗法带来了新机会。
