Retargeted Serine Integrases Enable Precise Large-Gene Insertion

Sangamo Therapeutics researchers have engineered the serine integrase Bxb1 to insert large DNA sequences at chosen genomic sites without requiring prior installation of its natural target sequence, according to a July 6, 2026, article in CRISPR Medicine News by Gorm Palmgren. The modular integrase, or MINT, platform retargets Bxb1 to the therapeutically relevant AAVS1 and TRAC loci. The platform achieved integration efficiencies of up to 35 percent in cell lines and 29 percent in primary human T cells. Serine integrases such as Bxb1 can integrate large DNA constructs with high precision but, until now, only at sites where their natural attachment sequence has already been introduced into the genome, typically via prime editing. This requirement added a layer of complexity to therapeutic development, the article stated. The report focused solely on the retargeting of Bxb1 through the MINT platform and the efficiencies observed at the specified loci in the described cell types.