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NEW PUBLICATION WITH MAG4C-AD

Local magnetic delivery of adeno-associated virus AAV2(quad Y-F)-mediated BDNF gene therapy restores hearing after noise injury.

Subhendu Mukherjee, Maya Kuroiwa, Wendy Oakden, Brandon T. Paul, Ayesha Noman, Joseph Chen, Vincent Lin, Andrew Dimitrijevic, Greg Stanisz, and Trung N. Le.

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."