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Virologie. Volume 12, Number 4, 275-92, Juillet-août 2008, revue

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Author(s) : M El Bakkouri, C MS Fabry, P Fender, G Schoehn

Summary : Adenoviruses are double stranded DNA non enveloped viruses. Although these viruses are widely studied for gene therapy and anticancer applications, fundamental knowledge of these viruses, especially from a structural point of view is lacking. This is probably partly responsible for the limited success of the first clinical trials. With these viruses, one of the main conditions necessary to use adenoviruses for therapeutic application is structural modification of the virus. Indeed, one has to retarget the virus to specific tissues and/or remove all the immunogenic loops present on the outside of the virus in order to limit the host immune response. To make these changes rationally, the structure of the capsid has to be known at atomic resolution. Today, electron microscopy is the only tool that enables us to have access to the structure of the entire virus, but only at intermediate resolution. Because the atomic structures of the adenovirus major capsid proteins are known, one can combine these structures with the electron microscopy based envelope to calculate a model of the capsid at quasi-atomic resolution. These kinds of models are useful to visualize and understand the complexity of the virus. Nevertheless, the structure of the entire capsid at atomic resolution will really be necessary to use the virus in a safe way.

Keywords : electronic microscopy, adenovirus, genic therapy, structure, cristallography