Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Development. 2021 Jan 20;148(2):dev195586. doi: 10.1242/dev.195586.
Efficient genetic manipulation in the developing central nervous system is crucial for investigating mechanisms of neurodevelopmental disorders and the development of promising therapeutics. Common approaches including transgenic mice and electroporation, although powerful in many aspects, have their own limitations. In this study, we delivered vectors based on the AAV9.PHP.eB pseudo-type to the fetal mouse brain, and achieved widespread and extensive transduction of neural cells. When AAV9.PHP.eB-coding gRNA targeting or was delivered to Cas9 transgenic mice, widespread gene knockout was also achieved at the whole brain level. Our studies provide a useful platform for studying brain development and devising genetic intervention for severe developmental diseases.
在发育中的中枢神经系统中进行高效的基因操作对于研究神经发育障碍的机制和开发有前途的治疗方法至关重要。常见的方法包括转基因小鼠和电穿孔，尽管在许多方面都很强大，但它们也有自己的局限性。在这项研究中，我们将基于 AAV9.PHP.eB 假型的载体递送到胎鼠大脑中，并实现了神经细胞的广泛和广泛转导。当 AAV9.PHP.eB 编码的靶向 或 的 gRNA 递送到 Cas9 转基因小鼠时，也在全脑水平上实现了广泛的基因敲除。我们的研究为研究大脑发育和设计严重发育性疾病的遗传干预提供了一个有用的平台。
