rAAV9.hAARS2-miR122BS

rAAV9.hAARS2-miR122BS is an experimental adeno-associated virus serotype 9 (AAV9) gene therapy vector developed by researchers at the University of Massachusetts Chan Medical School for the treatment of AARS2 deficiency. AARS2 encodes mitochondrial alanyl-tRNA synthetase, an enzyme critical for mitochondrial protein translation; mutations in this gene lead to infantile cardiomyopathy and late-onset leukodystrophy. The therapeutic construct delivers a functional human AARS2 transgene. To address the lethal hepatotoxicity observed with systemic delivery of ubiquitous AARS2 expression vectors in preclinical models, this specific version incorporates miR-122 binding sites (miR122BS) in the 3' untranslated region (UTR). This modification allows endogenous liver-specific microRNA-122 to silence the transgene in hepatocytes while maintaining therapeutic expression in target tissues such as the brain and heart. Preclinical data presented at ASGCT 2026 demonstrated that intracerebroventricular administration significantly extended survival in neuronal-specific knockout mouse models of leukodystrophy, and systemic administration rescued respiratory chain deficiency in heart-specific knockout models.

Other names

rAAV9.hAARS2-miR122 binding sitesrAAV-9.hAARS2-miR122 binding sitesrAAV 9.hAARS2-miR122 binding sites