Volume 32 Issue 4, July 2025

Cover Credit: RNA interference (RNAi) effectors delivered via the adeno-associated virus (AAV) vectors suppress harmful gene variants responsible for dominant disorders, offering therapeutic benefits. In this issue of Gene Therapy, researchers develop an AAV-RNAi strategy targeting neurodevelopmental GNAO1-related disorder characterized by early-onset epilepsy and movement disorders. The image shows iPSC-derived patient-specific neurons expressing a marker of the GABAergic neurotransmission pathway (GABBR1, red; nuclei, blue). The study demonstrates selective downregulation of the pathogenic GNAO1 c.607G>A following AAV-RNAi treatment. However, RNA sequencing analysis revealed safety issues associated with AAV transduction and RNAi activation in neurons.