Adenoviral and adeno-associated viral vector mediated gene transfer in the guinea pig cochlea.
Peripheral sensorineural hearing loss is a very common inner ear disorder affecting nearly 10% of the population. At present there is no cure for this disorder but gene therapy has been suggested as a potentially effective method for clinical treatment in the future. Thus we investigated the effectiveness of adenoviral (Ad) and adeno-associated viral (AAV) vectors to transduce the cochlea of guinea pigs. After direct injection into the basal turn of the cochlea, we found that both Ad and AAV vectors coding for the reporter genes lacZ or GFP readily transduced spiral ganglion cells. In addition, some transgene expression was detected in the stria vascularis after AAV-GFP injection. Gene expression persisted at least 8 weeks after viral vector injection. Present findings will help to develop future gene therapy protocols in the inner ear by using Ad and AAV coding for neurotrophins such as NT-3, BDNF, GDNF and VEGF.
Li Duan
Mao
M
Department of Clinical Neuroscience and Center for Hearing and Communication Research, Building M1-ENT, Karolinska Institutet, Karolinska Hospital, SE-171 76 Stockholm.
Bordet
Thierry
T
Mezzina
Mauro
M
Kahn
Axel
A
Ulfendahl
Mats
M
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003051:Cochlea / Q000502:physiology*; D015834:Cochlear Diseases / Q000628:therapy; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006168:Guinea Pigs; D007202:Indicators and Reagents / Q000378:metabolism; D007763:Lac Operon; D008164:Luminescent Proteins / Q000235:genetics
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins