title: Multicomponent nanoparticles as nonviral vectors for the treatment of Fabry disease by gene therapy.
abstract: OBJECTIVE
  Gene-mediated enzyme replacement is a reasonable and highly promising approach for the treatment of Fabry disease (FD). The objective of the present study was to demonstrate the potential applications of solid lipid nanoparticle (SLN)-based nonviral vectors for the treatment of FD.
  
  
  METHODS
  SLNs containing the pR-M10-αGal A plasmid that encodes the α-Galactosidase A (α-Gal A) enzyme were prepared and their in vitro transfection efficacy was studied in Hep G2 cells. We also studied the cellular uptake of the vectors and the intracellular disposition of the plasmid.
  
  
  RESULTS
  The enzymatic activity of the cells treated with the vectors increased significantly relative to the untreated cells, regardless of the formulation assayed. When the SLNs were prepared with protamine or dextran and protamine, the activity of the α-Gal A enzyme by the transfected Hep G2 cells increased up to 12-fold compared to that of untreated cells.
  
  
  CONCLUSIONS
  With this work we have revealed in Hep G2 cells the ability of a multicomponent system based on SLNs to act as efficient nonviral vectors to potentially correct low α-Gal A activity levels in FD with gene therapy.
authors.affiliation: Pharmacokinetics, Nanotechnology and Gene Therapy Group, Pharmacy Faculty, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
authors.forename: Aritz Pérez
authors.initials: AP
authors.lastname: Ruiz de Garibay
authors.forename: Diego
authors.initials: D
authors.lastname: Delgado
authors.forename: Ana
authors.initials: A
authors.lastname: Del Pozo-Rodríguez
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Solinís
authors.forename: Alicia Rodríguez
authors.initials: AR
authors.lastname: Gascón
mesh_terms: D000795:Fabry Disease / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D056945:Hep G2 Cells; D006801:Humans; D008055:Lipids / Q000008:administration & dosage; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D000519:alpha-Galactosidase / Q000378:metabolism
chemical_list: D008055:Lipids; D000519:alpha-Galactosidase
keywords: Fabry disease; gene therapy; nonviral vectors; solid lipid nanoparticles