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.