ArticleJournal of the Association for Research in Otolaryngology : JARO2025
Magnetic Targeting of AAV Gene Therapy for Inner Ear Following Systemic Delivery: Preliminary Findings and Transduction Pattern in Rat Cochlea.
Article in Journal of the Association for Research in Otolaryngology : JARO, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeDelivery of therapeutics to the inner ear is complicated by their inaccessible location and the presence of the blood-labyrinth barrier that restricts most blood-borne compounds from entering the inner ear. This study addresses the challenge of optimal delivery in treating inner ear disease, focusing on magnetic targeting gene therapy using adeno-associated virus (AAV).
methodsThe investigation explores three AAV serotypes (AAV2 Quad Mut, AAV2 pANC80L65, and AAV9 PHP.eB) delivered systemically, tagged with a brain-derived nerve growth factor (BDNF) transgene and GFP reporter protein, and captured with superparamagnetic nanoparticles. External magnets target AAV delivery to the Left ear of both male and female Long Evans rats. After 2 weeks, we evaluated tropism and transduction in both cochleae and assessed distribution in other major organs (heart, lung, liver, kidney, spleen, and brain) using immunohistochemistry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assays. Six animals were used for each experimental group.
resultsImmunofluorescence analysis demonstrated the qualitative distribution of AAVs in sensory cells and spiral ganglion neurons (SGN) in both ears. A significant increase in BDNF gene expression in the targeted left ear of rats administered AAV2 Quad Mut was observed. A single dose of magnetic targeting of AAV2 Quad Mut effectively transduced SGN and enhanced BDNF expression, leading to the restoration of ouabain-induced SGN loss and hearing loss (HL).
conclusionThese findings indicate the potential of magnetic targeting to direct gene therapy following systemic delivery, paving the way for future applications in the treatment of HL.
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