Prime assembly, a new genome engineering approach described in Nature, enables targeted integration of long DNA fragments into programmable genomic locations. The method uses CRISPR-targeted dual flap synthesis to build precise edits in a single step, aiming to expand beyond small prime-editing insertions. The researchers demonstrated targeted genomic integration and rearrangement at therapeutic loci in primary human cells, including exon recoding and megabase-scale rearrangements. Boston Children’s Hospital’s Daniel Bauer said the prime-editing basis may reduce off-target risks compared with approaches requiring double-strand breaks.