Researchers from Drexel University and UMass Chan published a 'silence‑and‑replace' AAV9 gene‑therapy strategy that prevented hereditary spastic paraplegia (HSP) symptoms in preclinical models, according to a Molecular Therapy report. The approach combines allele‑specific silencing with a replacement transgene to address both toxic gain‑of‑function and loss‑of‑function disease mechanisms. Preclinical outcome measures showed mitigation of motor deficits and neuropathology in treated animals. The dual‑action design aims to broaden applicability where pathogenic alleles coexist with haploinsufficiency, and the study establishes a translational blueprint for dominant neurogenetic disorders.