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Immune evasive DNA donors and recombinases license kilobase-scale writing

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Why This Matters

This collection of research highlights advancements in site-specific recombinases, transposons, and CRISPR-based systems for precise and efficient genome editing, including large DNA insertions and overcoming immune evasion. These innovations are crucial for developing safer, more versatile gene therapies and synthetic biology applications, directly impacting the future of personalized medicine and biotechnology. Understanding these tools' capabilities and limitations enables the industry to harness them for more effective genetic modifications in humans and other organisms.

Key Takeaways

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Olorunniji, F. J., Rosser, S. J. & Stark, W. M. Site-specific recombinases: molecular machines for the genetic revolution. Biochem. J. 473, 673–684 (2016).

Meinke, G., Bohm, A., Hauber, J., Pisabarro, M. T. & Buchholz, F. Cre recombinase and other tyrosine recombinases. Chem. Rev. 116, 12785–12820 (2016).

Jelicic, M. et al. Discovery and characterization of novel Cre-type tyrosine site-specific recombinases for advanced genome engineering. Nucleic Acids Res. 51, 5285–5297 (2023).

Smith, M. C. M., Brown, W. R. A., McEwan, A. R. & Rowley, P. A. Site-specific recombination by φC31 integrase and other large serine recombinases. Biochem. Soc. Trans. 38, 388–394 (2010).

Xu, Z. et al. Accuracy and efficiency define Bxb1 integrase as the best of fifteen candidate serine recombinases for the integration of DNA into the human genome. BMC Biotechnol. 13, 87 (2013).

Yarnall, M. T. N. et al. Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases. Nat. Biotechnol. 41, 500–512 (2023).

Durrant, M. G. et al. Systematic discovery of recombinases for efficient integration of large DNA sequences into the human genome. Nat. Biotechnol. 41, 488–499 (2023).

Wu, S. C.-Y. et al. piggyBac is a flexible and highly active transposon as compared to Sleeping Beauty, Tol2, and Mos1 in mammalian cells. Proc. Natl Acad. Sci. USA 103, 15008–15013 (2006).

Yusa, K., Zhou, L., Li, M. A., Bradley, A. & Craig, N. L. A hyperactive piggyBac transposase for mammalian applications. Proc. Natl Acad. Sci. USA 108, 1531–1536 (2011).

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