Long-term in vivo cochlear transgene expression mediated by recombinant adeno-associated virus.
Adeno-associated virus (AAV) integrated transgene expression within guinea pig cochlea has been previously documented. This article extends these studies by characterizing the AAV-mediated gene transfer for duration of transgene expression within the cochlea and its effect upon cochlear cytoarchitecture over a period of 6 months. All animals infused with AAV expressed the transgene product, bacterial beta-galactosidase (beta-gal) enzyme, in the spiral limbus, spiral ligament, spiral ganglion cells and the organ of Corti at 2-24 weeks after infusion. However, the level of beta-gal expression, as determined from intensity of immunoreactivity, was relatively lower at 24 weeks as compared with 2 weeks. The cellular and tissue architecture within the AAV-beta-gal perfused cochleae, harvested 2-8 weeks after AAV infusion, was generally intact, ie free from inflammation and cellular degeneration. However, cellular degeneration and degradation was apparent in the cochleae of some but not all animals harvested at 12 and 24 weeks after AAV infusion.
Lalwani
A
A
Department of Otolaryngology, Head and Neck Surgery, University of California San Francisco, USA.
Walsh
B
B
Reilly
P
P
Carvalho
G
G
Zolotukhin
S
S
Muzyczka
N
N
Mhatre
A
A
D000818:Animals; D003051:Cochlea / Q000473:pathology; D000229:Dependovirus; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006168:Guinea Pigs; D007150:Immunohistochemistry; D013997:Time Factors; D019076:Transgenes; D001616:beta-Galactosidase / Q000235:genetics
D001616:beta-Galactosidase