Team leader “Innovative Vectorology”, Scientific director “Translational Vector Core”
INSERM UMR1089, University of Nantes, CHU de Nantes, Nantes, FRANCE
Friday 20 September 2019 | 12:00 noon – ICGEB Trieste, ITALY
Chemical modification of Adeno- associated virus capsid to improve gene delivery
Host: S. Zacchigna
Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells and sustained maintenance of the viral genome. However, the conclusion from clinical data using these types of vectors is that there is a need to develop new AAVs with a higher transduction efficiency and specificity for relevant target tissues. To overcome these limitations, we chemically modified the surface of the capsid of AAV vectors. These modifications were achieved by chemical coupling of a ligand by formation of a thiourea function between the amino group of the capsid proteins and the reactive isothiocyanate motif incorporated into the ligand. This strategy does not require genetic engineering of the capsid sequence. The proof of concept was first evidenced using a fluorophore (FITC). Next, we coupled the N-acetylgalactosamine ligand onto the surface of the AAV capsid for an asialoglycoprotein receptor-mediated hepatocyte-targeted delivery. Taken together, our findings reveal the possibility of creating a specific engineered platform for targeting AAVs via chemical coupling.