Proposition De Stage Et / Ou De These »

Résumé: Recent progresses in the characterization of physical properties of viruses allows for the first time to investigate distinct virus cycle events at the single particle level [1]. Using an original combination of experimental approaches based on Atomic Force Microscopy (AFM) and statistical physics modelization, we propose to study the physical properties of Adeno-Associated Virus (AAV) particles in particular to define the parameters leading to capsid disassembly and ejection of the viral genome. AAV is a nonpathogenic parvovirus which is currently used as a gene transfer vector in gene therapy applications [2]. The vectors are composed by a recombinant DNA genome packaged into an icosahedral 20 nm-capsid which can be derived from at least 10 natural AAV serotypes. Interestingly, several studies indicate that the biological properties (virus entry, stability of the capsid, disassembly inside the cell nucleus) can greatly differ according to the AAV serotype used. Therefore, we would like to explore the physical properties of various AAV capsids serotypes to understand their differences in terms of stability, disassembly and release of their viral genome.