Gene transfer into the mammalian inner ear using HSV-1 and vaccinia virus vectors.
The introduction of foreign genes into cells has become an effective means of achieving intracellular expression of foreign proteins, both for therapeutic purposes and for experimental manipulation. Gene delivery to the nervous system has been extensively studied, primarily using viral vectors. However, to date less work has focused on gene delivery to the inner ear, and existing studies have primarily used adenovirus and adeno-associated virus. Using two recombinant viral vectors, herpes simplex type 1 (HSV-1), and vaccinia virus, bearing the Escherichia coli lacZ gene, we tested gene delivery to the guinea pig cochlea in vivo with beta-galactosidase staining as an assay. The HSV-1 and vaccinia virus vectors were both found to infect and elicit transgene expression successfully in many cells in the guinea pig cochlea, including cells in the organ of Corti. These data demonstrate the feasibility of gene delivery to the inner ear using these two viral vectors. Such techniques may facilitate study of the auditory systems, and might be used to develop gene therapy strategies for some forms of hearing loss.
Derby
M L
ML
Department of Neurology, Harvard Medical School and Massachusetts General Hospital, Boston 02114, USA.
Sena-Esteves
M
M
Breakefield
X O
XO
Corey
D P
DP
D000818:Animals; D003051:Cochlea / Q000201:enzymology / Q000473:pathology / Q000502:physiology; D007758:Ear, Inner / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006168:Guinea Pigs; D018259:Herpesvirus 1, Human / Q000235:genetics*; D007249:Inflammation / Q000473:pathology; D014018:Tissue Distribution / Q000502:physiology; D019076:Transgenes / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism
D001616:beta-Galactosidase