The objective of this project mixing organic chemistry and virology is to develop Adeno-Associated Vectors (AAVs) chemically modified to improve its safety and efficacy. AAVs are now becoming therapeutic products, however, clinical trials showed critical limitations: high doses are required to achieve therapeutic efficacy and off-target tissue transduction. ChemAAV will allow optimal cell targeting with enhanced therapeutic index and restricted biodistribution. These improvements will be obtained by chemical coupling of a ligand with targeting properties at the surface of the AAV, exploiting natural amino-acids of the capsid. The advantage of chemistry is the possibility to modify the AAV capsid with synthetic polymers, peptides, carbohydrates or even lipids that cannot be incorporated genetically. We will focus on two target cells for the proof-of-concept studies; hepatocytes and hematopoietic stem cells, with direct applications for liver, blood disorders, and immunodeficiencies.