A new Nature paper describes “prime assembly,” a genome engineering approach that enables targeted integration of long DNA fragments at programmable sites. Unlike earlier editing approaches that often rely on short edits or patient-by-patient customization, prime assembly uses CRISPR-targeted dual flap synthesis to tether engineered DNA fragments for precise, large permanent insertions. The authors report successful applications including targeted exon recoding and transgene integration, as well as megabase-scale rearrangements in primary human cells. The method is designed to function in both dividing and non-dividing cells and avoids double-strand breaks characteristic of other editing approaches. Researchers including Daniel Bauer at Boston Children’s Hospital said the platform’s prime-editing foundation could reduce off-target risk by constraining where edits begin and end. The work points toward more scalable “universal” gene therapy concepts that can support broader patient populations with fewer individualized constructs.
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