With the growing success of gene therapy clinical trials, adeno-associated virus vector (AAV) manufacturing and quality control requirements tend to increase. Our group aims at improving current large scale viral vector production systems, such as the Sf9/Baculovirus expression system. One of our main focuses is to optimize this production platform, by increasing the efficiency of packaging of the therapeutic transgene into AAV capsids, with the ultimate goal of improving the therapeutic efficacy of AAV-based products. We also develop novel analytical tools, based on next-generation sequencing (NGS), allowing us to identify and quantify the acid nucleic content of AAV particles. These approaches enables to improve the development of production processes to limit the encapsidation of nucleic acid contaminants in AAV vector lots. 

AAV TargetAAV target

Our group also focuses on the development of novel, chemically modified AAV particles, with increased therapeutic effect, at the interface between vectorology and chemistry. AAVs are efficient therapeutic platforms for the treatment of genetic diseases. Yet, past and ongoing clinical trials have highlighted some limitations, including the need for high doses to achieve therapeutic benefit, and the off-target transduction of various tissues. Chemically modified AAVs should enable to greatly decrease off-target effects, hence maximizing transduction in tissues of interest and improving the therapeutic index in AAV-based gene therapy. This will be possible through covalent coupling of tissue-specific ligands on surface exposed residues of the AAV capsid. The main advantage of this chemistry oriented approach is to be able to functionalize AAV particles with various ligands which could not be genetically encoded, including polymers, sugars or lipids.

Team members :

Eduard Ayuso, DVM, PhD – Team leader
Mathieu Mével, PhD, Senior scientist
Olivier Godfroy, PhD, Senior scientist
Elodie Landagaray, Post-doc
Magalie Penaud-Budloo, Post-doc
Aurelien Leray, PhD student
Emilie Lecomte, Engineer
Mohammed Bouzelha, Engineer