0000000001001711
AUTHOR
Anne E. Harasta
Glial Promoter Selectivity following AAV-Delivery to the Immature Brain
Recombinant adeno-associated virus (AAV) vectors are versatile tools for gene transfer to the central nervous system (CNS) and proof-of-concept studies in adult rodents have shown that the use of cell type-specific promoters is sufficient to target AAV-mediated transgene expression to glia. However, neurological disorders caused by glial pathology usually have an early onset. Therefore, modelling and treatment of these conditions require expanding the concept of targeted glial transgene expression by promoter selectivity for gene delivery to the immature CNS. Here, we have investigated the AAV-mediated green fluorescent protein (GFP) expression driven by the myelin basic protein (MBP) or gl…
Aav-based gene therapy approaches for the treatment of canavan disease
Background: The enzyme Aspartoacylase (ASPA) is normally expressed in oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). ASPA gene mutations cause Canavan Disease (CD), a devastating neurological disorder characterized by psychomotor retardation, and spongiform degeneration of central white matter in affected children. The lack of ASPA leads to the enrichment in its substrate N-acetyl aspartate (NAA) which is a biomarker of CD. With no available treatment and a pathology restricted to the CNS CD has been trialled by gene therapy. However, gene replacement approaches using neurotropic recombinant adeno-associated viral (rAAV) vectors have proved unsuccessful. It …