Gene Expression in the Mammalian Cochlea: A Study of Multiple Vector Systems

Abstract

Successful delivery of genes to the inner ear has been demonstrated using a variety of vectors and animal models. As our understanding of the molecular pathophysiology of hearing and balance disorders increases, the delivery of genes is becoming central to our ability to manipulate the function of the inner ear. This study evaluates the efficacy of gene transfer and the distribution of three different vector types within the inner ear. Adenovirus vectors, herpes virus vectors and liposomes carrying a plasmid with the green fluorescent protein or beta galactosidase marker genes and a CMV promoter were introduced into the inner ear of 3-month-old mice. The temporal bones and brain were then removed from the animals and examined for transgene expression. Distribution of staining in the treated ear was compared with distribution of staining in the contralateral inner ear. Staining for T cell markers was also carried out to determine inner ear immune response to gene transfer. Herpes virus vectors appear to target neurons most efficiently. Liposome vectors were least efficient in terms of gene transfer. Adenovirus vectors accomplished gene transfer to the widest variety of inner ear cells including auditory and vestibular hair cells. Newer generation adenovirus vectors promise less immune reaction and toxicity than traditional vectors and will be useful for both research and future clinical applications.