Gene transfer into guinea pig cochlea using adeno-associated virus vectors
Article first published online: 14 MAR 2008
Copyright © 2008 John Wiley & Sons, Ltd.
The Journal of Gene Medicine
Volume 10, Issue 6, pages 610–618, June 2008
How to Cite
Konishi, M., Kawamoto, K., Izumikawa, M., Kuriyama, H. and Yamashita, T. (2008), Gene transfer into guinea pig cochlea using adeno-associated virus vectors. J. Gene Med., 10: 610–618. doi: 10.1002/jgm.1189
- Issue published online: 15 MAY 2008
- Article first published online: 14 MAR 2008
- Manuscript Accepted: 29 JAN 2008
- Manuscript Revised: 21 JAN 2008
- Manuscript Received: 7 NOV 2007
- Research Grant from the Ministry of Education, Culture, Sports, Science and Technology in Japan. Grant Number: 18791245
- adeno-associated virus;
- gene transfer;
- guinea pig;
- hair cell;
- inner ear
Several genes are candidates for treating inner ear diseases. For clinical applications, minimally invasive approaches to the inner ear are desirable along with minimal side-effects.
Adeno-associated virus (AAV) was used as a vector into the guinea pig inner ear. Six AAV-cytomegalovirus hybrids (AAV-2/1, -2/2, -2/5, -2/7, -2/8 and -2/9) were infused into perilymph of the cochlea basal turn, an approach that could be used in cochlear implant surgery. At 7 days after injection, distribution of gene expression, hearing and morphology were evaluated. Adenoviral vector was also used to compare distributions of gene expression. Moreover, distribution of cell surface receptors of AAV in the cochlea was examined using immunohistochemistry.
Using the perilymphatic approach, adenovirus could be transferred to mesothelial cells lining the perilymph, but not sensory cells. Conversely, all AAV serotypes displayed tissue tropism to inner hair cells, with AAV-2/2 showing particularly efficient transfer to sensory cells. This tissue tropism of AAV could not be explained by the distribution of AAV receptors. Hearing and morphology were largely unaffected.
Our results indicate that AAV vector can be safely applied to the inner ear and AAV-2/2 offers a good tool for transferring transgenes into sensory cells of the inner ear efficiently without toxicity. Copyright © 2008 John Wiley & Sons, Ltd.