Prime assembly inserts gene-sized DNA without double-strand breaks

Researchers at Boston Children’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School published a genome-editing method called prime assembly in Nature on 16 September 2026. It writes gene-sized pieces of DNA into a chosen position without cutting both strands of the chromosome.

The mechanism borrows from prime editing, which David Liu’s laboratory developed. Prime assembly uses it to write one single-stranded flap into each strand of the genome at the edges of the region being replaced. Matching flaps on the incoming DNA anneal to them, the way fragments are joined in Gibson assembly. Because the two flaps mark where the replacement starts and where it ends, the boundaries are set by the operator rather than by the cell’s repair machinery.

Two consequences follow. There is no double-strand break, the lesion that drives the translocations and large deletions seen with nuclease editing. And the method does not depend on homology-directed repair, which only runs in dividing cells — so it works in cells that have stopped dividing, which is most of the cells in an adult body.

The reported applications are exon recoding, transgene integration and rearrangements at megabase scale. Daniel Bauer, co-senior author, says delivery into disease-relevant cells in a living body is the next problem. This is work in cells, not in patients.