Abstract
This study was designed to determine whether Coxsackie adenovirus receptor (CAR) and ανβ3/ανβ5 integrin co-receptors are involved in adenovirus gene transfer in the rat cochlea. We find that CAR and integrin co-receptors are expressed in every cell subtype transduced by the adenoviral vector Ad5 ΔE1–E3/cytomegalovirus/green fluorescent protein (GFP) on cochlear slices in vitro. The spiral ganglion neurons, which do not express CAR, were not transduced by the virus. Blocking these receptors by monoclonal antibodies decreased transgene expression, whereas disrupting tight junctions with ethylenediaminetetraacetic acid led to an increased transgene expression. However, sensory hair cells and strial cells also expressing CAR and αν integrins were not transduced by the vector. GFP expression was also studied in vivo. Perilymphatic perfusion of adenovirus in vivo did not affect hearing and only cells lining the perilymphatic spaces were transduced. Endolymphatic perfusion resulted in low-frequency hearing loss and although some cells of the organ of Corti were efficiently transduced, the sensory and the strial cells were not. Transduced sensory and strial cells were occasionally observed in cochleas after single shot of adenovirus. Pretreatment with anti-CAR and anti-αν antibodies decreases GFP expression in vivo, suggesting that the CAR/αν integrin pathway is involved in adenovirus transduction in the cochlea.
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Acknowledgements
We specially thank Dr Régis Nouvian and Prof Mondain for their helpful advice, Dr Lloyd for carefully editing the manuscript, and Sabine Ladrech and Nicole Renard for their technical assistance. This work was supported by the Spanish Ministry of Science and Technology to AB, the Generalitat de Catalunya (DURSI-ACI2001/8 and 2005SGR00008) to X Estivill (CRG) and the Instituto de Salud Carlos III (G03/203 and PI052347).
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Venail, F., Wang, J., Ruel, J. et al. Coxsackie adenovirus receptor and ανβ3/ανβ5 integrins in adenovirus gene transfer of rat cochlea. Gene Ther 14, 30–37 (2007). https://doi.org/10.1038/sj.gt.3302826
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DOI: https://doi.org/10.1038/sj.gt.3302826
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