Current Advances in Adeno-Associated Virus-Mediated Gene Therapy to Prevent Acquired Hearing Loss

Abstract

Adeno-associated viruses (AAVs) are viral vectors that offer an excellent platform for gene therapy due to their safety profile, persistent gene expression in non-dividing cells, target cell specificity, lack of pathogenicity, and low immunogenicity. Recently, gene therapy for genetic hearing loss with AAV transduction has shown promise in animal models. However, AAV transduction for gene silencing or expression to prevent or manage acquired hearing loss is limited. This review provides an overview of AAV as a leading gene delivery vector for treating genetic hearing loss in animal models. We highlight the advantages and shortcomings of AAV for investigating the mechanisms and preventing acquired hearing loss. We predict that AAV-mediated gene manipulation will be able to prevent acquired hearing loss.

Keywords: AAV transduction in vivo; AAV-mediated gene therapy; Acquired hearing loss.

Fig. 1

Schematic flow diagram of AAV vector use for inner ear therapy. A Packaging of plasmids (#1) encoding the gene of interest and a GFP marker requires co-transfection into HEK293T cells with capsid (#2) and helper (#3) plasmids. The capsid plasmid determines AAV particle structure and subtype, and the helper plasmid encodes the adenoviral genes E1, E2, E4, and VA that facilitate viral packaging. B Purified AAV particles are micro-injected into the inner ear of neonatal mice. Imaging and physiological tests evaluate recombinant gene expression, and its functional consequences once the mice reach designated experimental ages