Department of Biology, College of Science, Shantou University, Shantou, 515063, Guangdong, China.
Department of Clinical Laboratory Medicine, Chongqing University Jiangjin Hospital, Chongqing, China.
Transgenic Res. 2024 Oct;33(5):323-357. doi: 10.1007/s11248-024-00404-x. Epub 2024 Aug 19.
The application of rapidly growing CRISPR toolboxes and methods has great potential to transform biomedical research. Here, we provide a snapshot of up-to-date CRISPR toolboxes, then critically discuss the promises and hurdles associated with CRISPR-based nuclear genome editing, epigenome editing, and mitochondrial editing. The technical challenges and key solutions to realize epigenome editing in vivo, in vivo base editing and prime editing, mitochondrial editing in complex tissues and animals, and CRISPR-associated transposases and integrases in targeted genomic integration of very large DNA payloads are discussed. Lastly, we discuss the latest situation of the CRISPR/Cas9 clinical trials and provide perspectives on CRISPR-based gene therapy. Apart from technical shortcomings, ethical and societal considerations for CRISPR applications in human therapeutics and research are extensively highlighted.
CRISPR 工具盒和方法的迅速发展具有极大的潜力来改变生物医学研究。在这里，我们提供了最新的 CRISPR 工具盒的快照，然后批判性地讨论了基于 CRISPR 的核基因组编辑、表观基因组编辑和线粒体编辑的前景和障碍。我们讨论了在体内实现表观基因组编辑、体内碱基编辑和先导编辑、复杂组织和动物中的线粒体编辑，以及 CRISPR 相关转座酶和整合酶在靶向整合非常大的 DNA 有效载荷的基因组中的技术挑战和关键解决方案。最后，我们讨论了 CRISPR/Cas9 临床试验的最新情况，并提供了基于 CRISPR 的基因治疗的观点。除了技术上的缺点外，还广泛强调了 CRISPR 在人类治疗和研究中的应用的伦理和社会考虑。
