Abstract
Synthetic rewriting technologies, encompassing large-scale DNA assembly, transfer, maintenance, and rearrangement, enabled de novo synthesis or large-scale modifications of genomes. While significant progress has been made in model organisms of viruses, bacteria, and unicellular eukaryotes, their development in mammalian cells faces unique challenges. This review summarizes key breakthroughs in synthetic rewriting technologies, including megabase (Mb)-scale assembly of human DNA, yeast-mediated transfer methods, bottom-up human artificial chromosomes (HACs), and genome-scale rearrangement, along with emerging applications in constructing models and decoding genomes for mammals. These tools will expand functional engineering in mammals and deepen mechanistic insights into complex biological systems.
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Acknowledgements
This manuscript was supported by the National Key R&D Program of China [2024YFA0917400 for Y.W.], the National Natural Science Foundation of China [32471483 for Y.W.], and the Natural Science Foundation of Tianjin [23JCYBJC00220 for Y.W.].
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Y.W. conceived the original idea of this review. Y.W., Y.C., G.R.Z., Y.W., and Y.-J.Y. contributed to organizing the structure of the manuscript. Y.W., Y.C., G.-R.Z., Y.W., and Y.-J.Y. contributed to the literature review and wrote sections of the manuscript.
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Wang, Y., Cui, Y., Zhao, GR. et al. Synthetic rewriting technologies in mammalian cells. Nat Commun (2026). https://doi.org/10.1038/s41467-025-68066-9
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DOI: https://doi.org/10.1038/s41467-025-68066-9
