Long-term in vivo cochlear transgene expression mediated by recombinant adeno-associated virus

被引:75
作者
Lalwani, AK
Walsh, BJ
Reilly, PG
Carvalho, GJ
Zolotukhin, S
Muzyczka, N
Mhatre, AN
机构
[1] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, Oncol Mol Lab, Epstein Labs, San Francisco, CA 94143 USA
[2] Univ Florida, Gene Therapy Ctr, Gainesville, FL 32611 USA
[3] Univ Florida, Dept Microbiol & Mol Genet, Gainesville, FL 32611 USA
关键词
adeno-associated virus; beta-galactosidase; cochlea; hearing disorders;
D O I
10.1038/sj.gt.3300573
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:277 / 281
页数:5
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