Intravenous immunoglobulin prevents peripheral liver transduction of intrathecally delivered AAV vectors.

ABSTRACT: Gene therapy using neurotropic adeno-associated virus vectors represents an emerging solution for genetic disorders affecting the central nervous system. The first approved central nervous system-targeting adeno-associated virus gene therapy, Zolgensma®, for treating spinal muscular atrophy is administered intravenously at high doses that cause liver-associated adverse events in 20%-30% of patients. Intrathecal routes of vector administration, such as the intra-cisterna magna route, provide efficient gene transduction to central nervous system cells while reducing off-target liver transduction. However, significant levels of liver transduction often occur upon intra-cisterna magna vector delivery in preclinical studies. Using vectors expressing monoclonal antibody transgenes, we examined w

SUBMITTER: Horiuchi M 

PROVIDER: S-EPMC9593247 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature