AAV9-DARS2

AAV9-DARS2 is an investigational adeno-associated virus serotype 9 (AAV9) gene therapy designed for the treatment of Leukoencephalopathy with Brainstem and Spinal cord involvement and Lactate elevation (LBSL). LBSL is a rare, progressive neurological disorder caused by mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase (mt-ARS). The therapy utilizes an AAV9 vector to deliver a functional copy of the healthy DARS2 gene to the central nervous system, aiming to restore mitochondrial protein synthesis and prevent neurodegeneration. Preclinical studies presented at ASGCT 2026 demonstrated that intrathecal administration of AAV9-DARS2 vectors, utilizing promoters such as CAG, CBA, or MeCP2, successfully rescued degenerative phenotypes and significantly extended survival in Dars2 knock-out mouse models without signs of toxicity.