Title:Validation of a Generation 4 Phosphorus-Containing Polycationic Dendrimer for Gene Delivery Against HIV-1
VOLUME: 19 ISSUE: 29
Author(s):V. Briz, M.J. Serramia, R. Madrid, A. Hameau, Anne-Marie Caminade, J.P. Majoral and M.A. Munoz-Fernandez
Affiliation:Laboratorio Inmuno-Biologia Molecular, Instituto de Investigacion Sanitaria Gregorio Maranon (IiSGM); Hospital General Universitario Gregorio Maranón, C/Doctor Esquerdo 46, 28007 Madrid, Spain.
Keywords:Nanomedicine, phosphorus dendrimer, HIV, oligodeoxynucleotides, siRNA and gene therapy
Abstract:Gene therapy, in which oligomeric genetic material is carried into cells by nano-sized gene delivery vehicles to interfere with
gene expression, represents a promising approach for preventive therapy against HIV/AIDS pandemic. Herein, we evaluate the usefulness
of a phosphorus-containing dendrimer G4(NH+Et2Cl-)96 as a delivery agent of ODNs and siRNAs. G4(NH+Et2Cl-)96 formed stable
complexes with ODNs or siRNAs and exhibited very low cytotoxicity in Sup T1 cells or PBMC. Functional validation was performed by
using specific siRNA against HIV-1 Nef, siNEF to interfere in HIV-1 replication. G4(NH+Et2Cl-)96/siNEF dendriplex showed a high efficiency
in Nef silencing. Furthermore, in vitro treatment of HIV-infected PBMC with G4(NH+Et2Cl-)96/siNEF dendriplex significantly
reduced the viral replication. Our results prove the usefulness of phosphorus-containing dendrimers to deliver and transfect siRNA into
CD4-T cells as a potential alternative therapy in the HIV-1 infection.
