Zheng, YanjiangLi, YifeiZhou, KaiyuLi, TiangeVanDusen, Nathan J.Hua, Yimin2024-06-112024-06-112024-02-26Zheng Y, Li Y, Zhou K, Li T, VanDusen NJ, Hua Y. Precise genome-editing in human diseases: mechanisms, strategies and applications. Signal Transduct Target Ther. 2024;9(1):47. Published 2024 Feb 26. doi:10.1038/s41392-024-01750-2https://hdl.handle.net/1805/41384Precise genome-editing platforms are versatile tools for generating specific, site-directed DNA insertions, deletions, and substitutions. The continuous enhancement of these tools has led to a revolution in the life sciences, which promises to deliver novel therapies for genetic disease. Precise genome-editing can be traced back to the 1950s with the discovery of DNA's double-helix and, after 70 years of development, has evolved from crude in vitro applications to a wide range of sophisticated capabilities, including in vivo applications. Nonetheless, precise genome-editing faces constraints such as modest efficiency, delivery challenges, and off-target effects. In this review, we explore precise genome-editing, with a focus on introduction of the landmark events in its history, various platforms, delivery systems, and applications. First, we discuss the landmark events in the history of precise genome-editing. Second, we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human genome. Third, we introduce the current delivery systems used to deploy precise genome-editing components through DNA, RNA, and RNPs. Finally, we summarize the current applications of precise genome-editing in labeling endogenous genes, screening genetic variants, molecular recording, generating disease models, and gene therapy, including ex vivo therapy and in vivo therapy, and discuss potential future advances.en-USAttribution 4.0 InternationalCRISPR-Cas systemsGene editingGenetic therapyGenomeArticle