METHODS AND COMPOSITIONS FOR REDUCING NUCLEIC ACID VECTOR-INDUCED TOXICITY IN THE INNER EAR

The disclosure features compositions and methods for the treatment of inner ear dysfunction, such as hearing loss or vestibular dysfunction, that reduce inflammatory or cell-mediated immune toxicity in the inner ear, thereby improving transduction and therapeutic efficacy. The disclosure provides a variety of compositions that include a nucleic acid vector that contains a polynucleotide encoding a therapeutic agent operably linked to a ubiquitous promoter and inhibitor of inflammatory or immune cell signaling. The disclosed compositions and methods can be used to increase expression of the therapeutic agent in a subject, such as a human subject suffering from an inner ear dysfunction, while minimizing undesirable immune activation resulting from off-target expression of the target protein in immune cells of the inner ear.