This paper introduces INSTALL, a novel genome-engineering method that utilizes circular single-stranded DNA (cssDNA) to achieve large-scale genetic integration. Traditional techniques rely on double-stranded DNA, which often triggers toxic innate immune responses and limits the efficiency of non-viral gene delivery. By pairing these "immune-stealth" DNA donors with recombinase enzymes, the researchers successfully inserted kilobase-scale sequences into human cells and mice with high fidelity. The study demonstrates that INSTALL bypasses cellular defense mechanisms like the cGAS-STING pathway, significantly improving the safety and tolerability of systemic treatments. Ultimately, this technology provides a robust, non-viral alternative for permanent gene therapy and complex genomic writing.

References:

• Tou C J, Xie K, Ferreira da Silva J, et al. Immune evasive DNA donors and recombinases license kilobase-scale writing[J]. Nature, 2026: 1-11.