Local magnetic delivery of adeno-associated virus AAV2(quad Y-F)-mediated BDNF gene therapy restores hearing after noise injury.
Use of Mag4C-Ad to capture and magnetically locally deliver adeno-associated virus AAV2 in vivo.
Goal: gene therapy into the rat inner ear via minimally invasive magnetic targeting.
"Moderate noise exposuremay cause acute loss of cochlear synapses without affecting the cochlear hair cells and hearing threshold; thus, it remains “hidden” to standard clinical tests. This cochlear synaptopathy is one of the main pathologies of noise-induced hearing loss (NIHL). There is no effective treatment for NIHL, mainly because of the lack of a proper drug-delivery technique.We hypothesized that localmagnetic delivery of gene therapy into the inner ear could be beneficial for NIHL. In this study, we used superparamagnetic iron oxide nanoparticles (SPIONs) and a recombinant adeno-associated virus (AAV) vector (AAV2(quadY-F)) to deliver brain-derived neurotrophic factor (BDNF) gene therapy into the rat inner ear via minimally invasivemagnetic targeting.We found that themagnetic targeting effectively accumulates and distributes the SPION-tagged AAV2(quadY-F)-BDNFvector into the inner ear.Wealso found thatAAV2(quadY-F) efficiently transfects cochlear hair cells and enhances BDNF gene expression. Enhanced BDNF gene expression substantially recovers noise-inducedBDNFgene downregulation, auditory brainstem response (ABR) wave I amplitude reduction, and synapse loss. These results suggest that magnetic targeting of AAV2(quad Y-F)-mediated BDNF gene therapy could reverse cochlear synaptopathy after NIHL."