St. Jude researchers published an engineering study of CRISPR‑associated transposons (CASTs) that advances programmable, RNA‑guided DNA integration. The team built a dual genetic screen to measure activity and specificity across large CAST libraries and used site‑saturation mutagenesis to identify mutations in core transposition proteins that raise activity up to four‑fold while preserving high on‑site specificity. Authors report the wild‑type V‑K CAST already displayed 88–95% on‑target specificity; the engineered variants improved integration rates in heterologous systems. The work, in Nucleic Acids Research, illuminates mechanistic trade‑offs between activity and precision and provides a path to CASTs tailored for therapeutic gene insertion. Translational steps remain: the authors cited limited activity in human cells as the next hurdle and work to adapt optimized CASTs for mammalian delivery and safety testing.