A Novel Vestibular Approach for Gene Transfer into the Inner Ear

• Published in: Audiology & neurotology Vol. 7; no. 6; pp. 324 - 334
• Main Authors: Praetorius, Mark, Knipper, Marlies, Schick, Bernhard, Tan, Justin, Limberger, Annette, Carnicero, Estela, Alonso, Maria Teresa, Schimmang, Thomas
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.11.2002
• Subjects: Animals; beta-Galactosidase - metabolism; Biological and medical sciences; Biotechnology; Cochlea - enzymology; Cochlea - pathology; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene therapy; Gene Transfer Techniques - instrumentation; Genetic Therapy - methods; Genetic Vectors; Health. Pharmaceutical industry; Herpes Simplex - enzymology; Herpes Simplex - pathology; Herpes Simplex - therapy; Herpesvirus 1, Human - enzymology; Herpesvirus 1, Human - genetics; Industrial applications and implications. Economical aspects; Lac Operon - genetics; Medical sciences; Non tumoral diseases; Original Paper; Otorhinolaryngology. Stomatology; Rats; Rats, Wistar; Vestibule, Labyrinth - enzymology; Vestibule, Labyrinth - pathology; Cochlea; Herpes simplex virus 1; Gene therapy; Utriculus; Inner ear therapy; Amplicon vector; Performance evaluation; Rat; Herpesviridae; Internal ear disease; Treatment efficiency; Alphaherpesvirinae; Rodentia; Experimental study; Inner ear; Virus; Vertebrata; Mammalia; Herpesvirus hominis 1; Animal; ENT disease; Technique; Utricle; Vector
• ISSN: 1420-3030; 1421-9700
• DOI: 10.1159/000066157

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 β-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, β-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.