Progress in targeted gene editing by programmable endonucleases has paved the way for their use in gene therapy. Particularly, Cas9 is an endonuclease with high activity and flexibility, rendering it an attractive option for therapeutic applications in clinical settings. Many disease-causing mutations could potentially be corrected by this versatile new technology. In addition, recently developed switchable Cas9 variants, whose activity can be controlled by an external stimulus, provide an extra level of spatiotemporal control on gene editing and are particularly desirable for certain applications. Here, we discuss the considerations and difficulties for implementing Cas9 to in vivo gene therapy. We put particular emphasis on how switchable Cas9 variants may resolve some of these barriers and advance gene therapy in the clinical setting.

中文翻译：

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将可切换的Cas9变体应用于体内基因编辑以用于治疗应用。

可编程核酸内切酶在靶向基因编辑方面的进展为它们在基因治疗中的应用铺平了道路。特别地，Cas9是具有高活性和柔性的核酸内切酶，使其成为临床环境中治疗应用的有吸引力的选择。这种多用途的新技术可能会纠正许多致病突变。另外，最近开发的可切换Cas9变体的活性可以通过外部刺激来控制，提供了对基因编辑的时空控制的额外水平，并且对于某些应用是特别期望的。在这里，我们讨论将Cas9应用于体内基因治疗的考虑因素和困难。我们特别强调可切换的Cas9变体如何解决这些障碍，并在临床环境中推进基因治疗。