Authors
Kerui Huang, Jianhong Tian, Wenyan Zhao, Siqin Zhang, Lixuan Xiang, Meiqing Yang, Lu Liu, Yazhou Huang, Ningyun Zhang, Lei Sun, Peng Xie, Nanyu Kuang, Hong Zhou, Chengfeng Qiu, Jun Yan, Xiaocheng Jiang, Qiang Tu, Yun Wang, Haoliang Hu, Youming Zhang
Published in
iMetaOmics. Volume 3. Issue 3. Pages e70115. Epub Jul 26, 2026.
Abstract
Genomic manipulation has advanced from stochastic nuclease-mediated disruption toward programmable, deterministic precision. Early clustered regularly interspaced short palindromic repeats (CRISPR) strategies enabled targeted mutagenesis through double-strand 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-scale writers, such as CRISPR-associated transposases and recombinase-based bridge RNAs, which enable the integration of multi-kilobase 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-throughput screening transform the genome from a static substrate into a more dynamic model for complex, synthetic functional design.
PMID:
42891351
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.
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