AAV9-ZC4H2

AAV9-ZC4H2 is an adeno-associated virus serotype 9 (AAV9) gene therapy candidate designed for the treatment of ZC4H2-Associated Rare Disorders (ZARD). ZARD is an ultra-rare X-linked neurodevelopmental condition caused by loss-of-function mutations in the ZC4H2 gene, which lead to impaired BMP-SMAD signaling and disrupted cortical development. Developed by researchers at the University of California Davis, AAV9-ZC4H2 delivers a codon-optimized version of the ZC4H2 gene to restore protein expression and normalize downstream signaling pathways, including BMPR2 and pSMAD1/5. Preclinical studies in patient-derived cortical organoids have shown that the therapy can rescue cellular phenotypes, normalize organoid growth, and improve neuronal complexity, supporting its potential as a therapeutic strategy for ZARD.