New method inserts long DNA segments at precise genome locations

Researchers at Boston Children's Hospital developed a technique called prime assembly that builds on prime editing to insert DNA fragments up to 12.1 kilobases at specific genome sites. The method uses single-stranded DNA flaps to control exactly where the replacement starts and ends, potentially addressing genetic diseases caused by many mutations. The approach is still early but could enable mutation-agnostic therapies.

Prime assembly was developed at Boston Children's Hospital and published in Nature. The technique creates single-stranded DNA flaps at chosen genomic positions, which guide the integration of DNA segments up to 12.1 kilobases in size—large enough to contain entire gene fragments. This allows a single editing step to produce a permanent genetic change.

The method proved effective in both dividing and non-dividing cells, and in some comparisons it outperformed existing targeted integration techniques. Unlike certain current approaches, prime assembly avoids deliberately creating double-strand breaks, which can stress cells. The research remains preclinical, with experiments conducted in cell lines and primary cells from healthy donors, and delivery methods for use inside living organisms have yet to be developed.