title: A novel vestibular approach for gene transfer into the inner ear.
abstract: The aim of gene transfer to the cochlea and vestibular organ is to protect the inner ear from different disorders. Although various vectors for gene delivery have been used with some success, there remains a need for a reliable transfer of genes into the inner ear without damaging cochlear function. Here, we have tested a novel application method for gene transfer into the rat inner ear in vivo using herpes simplex virus type-1(HSV-1)-based amplicon vectors. Our goal was to find an entry route into the inner ear that leaves its function intact. Besides other non-invasive and invasive application techniques, we applied the viral vector via injection through a small opening of the utriculus. Using this method, efficient -galactosidase reporter gene expression was achieved in nearly all neurons in the vestibulum and cochlea, without functional hearing deficits. At the time point of maximal expression 5 days after injection, -galactosidase activity was also observed in axonal fibres and synaptic endings close to inner and outer hair cells. Our results thus describe an efficient and reliable protocol for short-term expression of potential therapeutic genes in the neuronal compartment of the inner ear.
authors.affiliation: Department of Otorhinolaryngology, University Hospitals of the Saarland, Homburg/Saar, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Praetorius
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schick
authors.forename: Justin
authors.initials: J
authors.lastname: Tan
authors.forename: Annette
authors.initials: A
authors.lastname: Limberger
authors.forename: Estela
authors.initials: E
authors.lastname: Carnicero
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Alonso
authors.forename: Thomas
authors.initials: T
authors.lastname: Schimmang
mesh_terms: D000818:Animals; D003051:Cochlea / Q000201:enzymology* / Q000473:pathology; D015870:Gene Expression; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006561:Herpes Simplex / Q000201:enzymology* / Q000473:pathology / Q000628:therapy*; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D007763:Lac Operon / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D014722:Vestibule, Labyrinth / Q000201:enzymology / Q000473:pathology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase