Adenoviral-mediated gene transfer into guinea pig cochlear cells in vivo

Abstract

Loss of ganglion cells is a common and irreversible complication of hair cell loss in the cochlea. Gene transfer could potentially be used to prevent this neuronal degeneration and other pathologies in the cochlea. Human adenoviruses should provide a feasible gene transfer vehicle for transducing the quiescent cochlear neurons and organ of Corti epithelium. We now describe in vivo experiments in which a replication-deficient adenoviral vector, Ad.RSV ntlacZ was injected into the perilymphatic fluid of six normal guinea pigs. Postoperative recovery of animals was complete. Inner ear tissues were assessed for histology and for presence of lacZ-positive cells 1 or 2 weeks after the injection. A large number of blue (lacZ-positive) cells were observed in the neural, epithelial and connective tissues of the cochlea. In four ears spiral ganglion cell infection exceeded 50%, throughout the length of the cochlear spiral. No major pathology was detected in the organ of Corti and other cochlear tissues, and no infection was present in the vestibular tissues or the contralateral cochlea. Immunocytochemical assessment of T cells revealed an increase in the number of lymphocytes in the connective tissue lining the perilymphatic spaces. We conclude that efficient gene transfer into multiple types of cochlear cells in vivo can be achieved without major morphological signs of pathology or toxicity.