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Flying under the radar: immune-evasive DNA for genome engineering

Frances Y. Tsai¹ , Samuel H. Sternberg^1,2,*

¹Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA
²Howard Hughes Medical Institute, Columbia University, New York, NY, USA
* Correspondence: Samuel H. Sternberg(shsternberg@gmail.com)

A recent study by Tou et al. introduces integration through nucleus-synthesized template addition of large lengths (INSTALL), a recombinase-based genome engineering strategy that uses circular single-stranded DNA donors with partially duplexed regions to reduce innate immune activation and toxicity associated with conventional double-stranded DNA delivery. This donor redesign improves non-viral DNA integration in primary human cells and in vivo.

https://doi.org/10.1038/s41422-026-01257-1

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