Modification of adenovirus type 5 tropism for a preferential transduction of human papillomavirus-positive cancer cells
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Human group C adenoviruses can infect many cell types, and this is due to the widespread expression of their receptor, the coxsackievirus and adenovirus receptor (CAR). Adenovirus vectors for cancer gene therapy could be significantly improved if their tropism were restricted to tumor cells. In this work, previously identified peptides that target human papillomaviruses (HPV)-transformed cells were inserted into the HI loop of a non-CAR-binding fiber. These modified fiber proteins were able to assemble into adenovirus particles. We demonstrated that these modifications ablated the native tropism of adenovirus type 5, and these modified adenoviruses were shown to preferentially transduce HPV-transformed cell lines.
We acknowledge Dan J. Von Seggern (TSRI, La Jolla, CA, USA) for providing us reagents. We thank Philip Robinson (Département de Pharmacologie, Université Victor Ségalen Bordeaux 2, Bordeaux, France) for critical reading of the manuscript. This work was supported by the ULP, CNRS, ARC, the Ligue Nationale Contre Le Cancer Comité du Haut Rhin and the Cancéropôle-Grand-EST. M.L. and C.B-L. were supported by scholarships of the Ministère de la Recherche (M.L. and C.B-L.) and the Ligue Régionale Contre le Cancer (ML).
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