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Early clustered regularly interspaced short palindromic repeats (CRISPR) strategies enabled targeted mutagenesis through double\u2010strand breaks; however, their therapeutic application is limited by genotoxicity, chromosomal instability, and dependence on endogenous repair pathways that are difficult to predict. In this review, we examined the transition from gene editing to genome writing, an approach that decouples genomic modification from host repair pathways to better balance efficiency, precision, and payload delivery. We also discussed the principles of precision technologies, including base and prime editors, and described emerging large\u2010scale writers, such as CRISPR\u2010associated transposases and recombinase\u2010based bridge RNAs, which enable the integration of multi\u2010kilobase synthetic modules. Beyond enzymatic mechanisms, we further considered the combined use of generative artificial intelligence, structural biology, and novel delivery architectures as potential strategies to overcome current biological limitations. Taken together, these developments point toward Generative Biology, in which computational design and high\u2010throughput screening transform the genome from a static substrate into a more dynamic model for complex, synthetic functional design.<\/jats:p>","DOI":"10.1002\/imo2.70115","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T08:07:51Z","timestamp":1785053271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Strategies and mechanisms of precision genome engineering: From gene editing to genome writing"],"prefix":"10.1002","volume":"3","author":[{"given":"Kerui","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Technology Shandong University Qingdao China"},{"name":"State Key Laboratory of Microbial Technology (Changde R&amp;D Base), College of Synthetic Biology Industry, Institute of Synthetic Biology Industry Hunan University 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