Multiple advances in 2025 signaled a turning point for in vivo gene therapies as delivery, targeting and clinical strategies matured. Industry reviews conclude the year saw meaningful progress toward safer, more effective in‑body editing and gene replacement approaches, with several programs advancing into clinical testing and new preclinical platforms demonstrating improved tropism and control. As one concrete example, researchers reported a silence‑and‑replace SPAST‑AAV9 gene therapy that prevented hereditary spastic paraplegia (HSP) symptoms in preclinical models, combining RNA silencing and gene replacement within a single AAV9 vector. The Molecular Therapy study highlighted translational promise and underscored delivery and payload engineering advances that are enabling disease‑modifying in vivo approaches. Regulators, investors and translational scientists will watch whether 2026 clinical readouts replicate the preclinical gains and how safety, vector dosing and durability issues are managed in human trials.