Industry reviews flagged 2025 as a breakthrough year for in vivo gene therapies, noting progress on delivery, efficacy, and clinical translation. Supporting that narrative, a preclinical study reported a silence-and-replace SPAST-AAV9 gene therapy that prevented symptoms in hereditary spastic paraplegia models, demonstrating a combined strategy to tackle gain-of-toxicity and loss-of-function disease mechanisms. Collectively, the pieces underscore both broad field advances and a specific program that may move toward clinical testing as delivery and durability data mature.