Targeted DNA integration; plus Janssen’s small molecule dengue inhibitor and more

A team from Columbia University, led by Dahlia Biosciences Inc. co-founder Samuel Sternberg, reported in Nature Biotechnology programmable integration of large DNA sequences in human cells without the induction of double-stranded breaks — a safety limitation of CRISPR–Cas9 genome engineering — using Type I-F CRISPR-associated transposases (CASTs).

The team screened and optimized CAST systems from a range of bacteria, and identified the bacterial ATPase ClpX as an accessory factor that enhanced genomic integration by more than two orders of magnitude. ATPase ClpX promotes dissociation of the CAST complex after the transposition reaction is completed, enabling subsequent gap repair...