Widespread labeling and genomic editing of the fetal central nervous system by in utero CRISPR AAV9-PHP.eB administration.
Widespread labeling and genomic editing of the fetal central nervous system by in utero CRISPR AAV9-PHP.eB administration.
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DOI：
10.1242/dev.195586
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发表时间：
2021-01-20
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
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作者：
Hu S;Yang T;Wang Y
在发育中的中枢神经系统中进行有效的遗传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子宫内电穿孔，虽然在许多方面很强大，但有其自身的局限性。在本研究中，我们将基于AAV9.PHP.eB假型的载体递送到胎鼠脑中，并实现了神经细胞的广泛和广泛的转导。当将靶向PogZ或Depdc 5的AAV 9.PHP. eB编码gRNA递送至Cas9转基因小鼠时，也在全脑水平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。总结：子宫内CRISPR AAV 9-PHP.eB提供了一个强大的平台，可以有效地操纵发育中CNS的基因表达，以研究神经发育障碍的机制。
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 in utero 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 PogZ or Depdc5 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. Summary: In utero CRISPR AAV9-PHP.eB provides a powerful platform to efficiently manipulate gene expression in the developing CNS to investigate mechanisms of neurodevelopmental disorders.