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Peer-reviewedCC BYIMetaOmics

Strategies and mechanisms of precision genome engineering: From gene editing to genome writing

  • Kerui Huang1,2
  • Jianhong Tian3
  • Wenyan Zhao1
  • Siqin Zhang1
  • Lixuan Xiang1
  • Meiqing Yang1
  • Liu Ls4
  • Y Huang5
  • Ningyun Zhang6
  • Lei Sun7
  • Peng Xie1
  • Nanyu Kuang8,9
8 more authors
  • Hong Zhou10
  • Chengfeng Qiu11
  • Jun Yan12
  • Xiaofei Jiang3
  • Qiang Tu1,2,13
  • Yue Wang1
  • Haoliang Hu1,14
  • Y M Zhang1,2,13
14 affiliations
  1. 1State Key Laboratory of Microbial Technology (Changde R&D Base), College of Synthetic Biology Industry, Institute of Synthetic Biology Industry Hunan University of Arts and Science Changde China
  2. 2State Key Laboratory of Microbial Technology Shandong University Qingdao China
  3. 3College of Life Sciences Hunan Normal University Changsha China
  4. 4School of Life Sciences Sun Yat‐Sen University Guangzhou China
  5. 5Central South University Xiangya School of Medicine Affiliated Changde Hospital (The first people's hospital of Changde city) Changde China
  6. 6Shanghai Collaborative Innovation Center of Plant Germplasm Resources Development, Shanghai Engineering Research Center of Plant Germplasm Resources College of Life Sciences, Shanghai Normal University Shanghai China
  7. 7Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory Changsha China
  8. 8Institute of Science and Technology for Brain‐Inspired Intelligence, Fudan University Shanghai China
  9. 9Neuroimaging Research Branch, National Institute on Drug Abuse National Institutes of Health Baltimore Maryland USA
  10. 10Department of Radiology, The First Affiliated Hospital, Hengyang Medical School University of South China Hengyang China
  11. 11Evidence‐Based Medicine and Clinical Research Center Hunan University of Medicine General Hospital Huaihua China
  12. 12Hunan Provincial Demonstration Center of Forestry Seedling Breeding Changsha China
  13. 13Yuelushan Laboratory Changsha China
  14. 14The Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Pharmaceutic Science, Health Science Center Hunan Normal University Changsha China
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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.

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Cite

BibTeXRIS
BibTeX
@article{huang2026strategies,
  title = {{Strategies and mechanisms of precision genome engineering: From gene editing to genome writing}},
  author = {Kerui Huang and Jianhong Tian and Wenyan Zhao and Siqin Zhang and Lixuan Xiang and Meiqing Yang and Liu Ls and Y Huang and Ningyun Zhang and Lei Sun and Peng Xie and Nanyu Kuang and Hong Zhou and Chengfeng Qiu and Jun Yan and Xiaofei Jiang and Qiang Tu and Yue Wang and Haoliang Hu and Y M Zhang},
  journal = {IMetaOmics},
  year = {2026},
  month = jul,
  doi = {10.1002/imo2.70115},
  url = {https://europepmc.org/article/PMC/PMC13674456},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Strategies and mechanisms of precision genome engineering: From gene editing to genome writing
AU  - Kerui Huang
AU  - Jianhong Tian
AU  - Wenyan Zhao
AU  - Siqin Zhang
AU  - Lixuan Xiang
AU  - Meiqing Yang
AU  - Liu Ls
AU  - Y Huang
AU  - Ningyun Zhang
AU  - Lei Sun
AU  - Peng Xie
AU  - Nanyu Kuang
AU  - Hong Zhou
AU  - Chengfeng Qiu
AU  - Jun Yan
AU  - Xiaofei Jiang
AU  - Qiang Tu
AU  - Yue Wang
AU  - Haoliang Hu
AU  - Y M Zhang
PY  - 2026
DA  - 2026/07/26
JO  - IMetaOmics
DO  - 10.1002/imo2.70115
UR  - https://europepmc.org/article/PMC/PMC13674456
AB  - 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.
SN  - 2996-9514
SN  - 2996-9506
ER  -