Coating of viral vectors with lipid vesicles as stealth systems for use in the treatment of monogenic diseases


Centelles Jost, Marine  


Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a gene encoding for a protein called dystrophin that helps keep muscle cells intact. While there is no known cure for DMD, there are treatments that can help control symptoms. For this reason and because it is a monogenic disease, DMD is an ideal therapeutic target to introduce new therapeutic approaches based on the design of nanovehicles, for gene therapy. Gene therapy aims to restore the missing dystrophin by providing a working copy of it. Current strategies for gene transfer include the use of adeno-associated viral (AAV) vectors, because they can infect skeletal and cardiac muscle very efficient, are able to infect nondividing cells and have a very good safety profile. However, AAVs may have limitations, due to pre-existing immunity of the AAV capsid which may reduce the efficiency of transduction and is currently a reason for exclusion from clinical trials. Several methods are currently being studied to reduce recognition by neutralizing antibodies (NAbs), of which the lipid coating, and in our case, by means of exosomes. Exosome-mediated encapsulation can protect viruses from neutralizing antibodies, promote viral infectivity, and prevent early clearance of viral vectors. As for therapeutic purposes, the intrinsic capacity of EVs for intercellular communication, their small size, and their natural origin, are promising characteristics that make these nanovehicles advanced systems for effective gene delivery, where the encapsulation of the viral particle containing nucleic acids encoding the therapeutic gene is crucial. The main objective of this Final Degree Project is to carry out the design of exogenous encapsulation strategies for rAAV, based on electroporation and permeabilization of extracellular vesicles, to evaluate the encapsulation efficiency of these vesicles.
The results obtained have shown that more research is needed in this field to find other more promising alternatives for the efficient encapsulation of rAAV in previously isolated EVs, in order to achieve an effective treatment for DMD in the future.



Fornaguera i Puigvert, Cristina
Guerra Rebollo, Marta


IQS SE - Undergraduate Program in Pharmacy