Hearing preservation after inner ear gene therapy: the effect of vector and surgical approach.
Over seventy studies have examined the potential of gene therapy in the inner ear. For the most part, they have focused on adenoviral vectors and delivery into the cochlea. Most studies have emphasized looking at the expression of marker genes driven by a CMV promoter and have used first-generation adenoviral constructs. E1/E3/E4 deleted adenoviral vectors carrying the green fluorescent protein (GFP) gene were injected into the round window, the basal turn of the cochlea (via a cochleostomy) or into the superior semicircular canal. Hearing was then tested 24 h after viral gene transfer. Large vector titers in small volumes of fluid were well tolerated with the round window approach resulting in complete hearing preservation with transfer of GFP to hair cells and spiral ganglion cells. Injection of comparable doses of vector into a basal turn cochleostomy resulted in high-frequency hearing loss. Addition of a pancaspase inhibitor protected hearing when larger volumes of fluid were administered to the inner ear.
Praetorius
Mark
M
Department of Otolaryngology, University Hospital of the Saarland, Homburg/Saar, Germany.
Baker
Kim
K
Weich
Corina M
CM
Plinkert
Peter K
PK
Staecker
Hinrich
H
D000256:Adenoviridae; D000818:Animals; D016057:Evoked Potentials, Auditory, Brain Stem; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006309:Hearing / Q000502:physiology*; D034381:Hearing Loss / Q000517:prevention & control*; D007202:Indicators and Reagents; D007759:Labyrinth Diseases / Q000628:therapy; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008808:Mice, Inbred CBA
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins