Researchers described a circular single‑stranded DNA donor approach that permits kilobase‑scale, non‑viral insertions while minimizing innate immune activation. The method—reported in Nature and described by teams including Ben Kleinstiver and collaborators at Massachusetts General Hospital and Full Circles Therapeutics—uses immune‑evasive donor designs and recombinase‑compatible short double‑stranded handles to enable large payload integration. Lead data show effective liver integration in mice with markedly improved tolerability versus conventional double‑stranded donors. Authors position the technology as a step toward generalizable genetic medicines that avoid bespoke correction of individual mutations by inserting full gene cassettes at programmable loci.