A new paper in Nature describes “prime assembly,” a genome engineering method that enables long DNA fragments to be integrated at precise, programmable genomic positions. The approach uses CRISPR-targeted dual flap synthesis and is designed to work in both dividing and non-dividing cells, expanding beyond the shorter edits typical of prime editing. Researchers report applications including targeted exon recoding, transgene integration, and megabase-scale rearrangements in primary human cells, aimed at therapeutically relevant loci. The authors position prime assembly as an option for “universal” gene therapies by targeting common disease-relevant genomic sites rather than relying on highly individualized edits. The technique also aims to reduce certain safety concerns by avoiding reliance on double-strand breaks and double-strand donors, while using the prime editing framework to drive more targeted integration boundaries.
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