Resumen de Functionalised SLNs-based nanovectors for gene therapy in Fabry disease: The liver as an α-Galactosidase A factory
Julen Rodríguez Castejón, Itziar Gómez Aguado, Marina Beraza Millor, María Ángeles Solinís Aspiazu, Ana del Pozo Rodríguez, Alicia Rodríguez Gascón
Fabry disease (FD) is a monogenic X-linked metabolic disorder caused by mutations in the gene that encodes the enzyme α-Galactosidase A (α-Gal A). A deficiency of enzyme activity leads to a progressive deposition of glycosphingolipids within the lysosomes of cells, predominantly in vascular endothelial and smooth muscle cells. The liver is a highly specialized organ in protein synthesis, which, after transfection with the appropriate nucleic acid, could act as an α-Gal A production factory to later release it and restore the enzyme deficiency in affected organs. The delivery of nucleic acids to hepatocytes with non-viral vectors is challenging; however, it can be enhanced by functionalizing the carriers with different ligands. Solid Lipid Nanoparticles (SLNs) are regarded as one of the most promising non-viral gene delivery systems. One of their main advantages is the wide versatility they offer. In fact, SLNs can be decorated easily with polysaccharides to control the biodistribution in vivo. The objective of the present work is the design of SLNs-based nanovectors decorated with polysaccharides and the evaluation of their capacity to transfect a liver-derived cell line (Hep G2).
