CRISPR-Cas clinical trials have begun, offering a first glimpse at how DNA and RNA targeting could enable therapies for many genetic and epigenetic human diseases. The speedy progress of CRISPR-Cas from discovery and adoption to clinical use is built on decades of traditional gene therapy research and belies the multiple challenges that could derail the successful translation of these new modalities. Here, we review how CRISPR-Cas therapeutics are translated from technological systems to therapeutic modalities, paying particular attention to the therapeutic cascade from cargo to delivery vector, manufacturing, administration, pipelines, safety, and therapeutic target profiles. We also explore potential solutions to some of the obstacles facing successful CRISPR-Cas translation. We hope to illuminate how CRISPR-Cas is brought from the academic bench toward use in the clinic.

中文翻译：

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转化 CRISPR-Cas 疗法：方法和挑战。


CRISPR-Cas 临床试验已经开始，首次展示了 DNA 和 RNA 靶向如何能够治疗许多遗传性和表观遗传性人类疾病。 CRISPR-Cas从发现、采用到临床使用的快速进展建立在数十年的传统基因治疗研究的基础上，并且掩盖了可能阻碍这些新模式成功转化的多重挑战。在这里，我们回顾了 CRISPR-Cas 疗法如何从技术系统转化为治疗方式，特别关注从货物到递送载体、制造、管理、管道、安全性和治疗靶点概况的治疗级联。我们还探索了针对 CRISPR-Cas 成功翻译所面临的一些障碍的潜在解决方案。我们希望阐明 CRISPR-Cas 如何从学术平台走向临床应用。