title: Validation of a generation 4 phosphorus-containing polycationic dendrimer for gene delivery against HIV-1.
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.
authors.affiliation: Laboratorio Inmuno-Biologia Molecular, Instituto de Investigacion Sanitaria Gregorio Maranon (IiSGM); Hospital General Universitario Gregorio Maranon, C/Doctor Esquerdo 46, 28007 Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Briz
authors.forename: M J
authors.initials: MJ
authors.lastname: Serramía
authors.forename: R
authors.initials: R
authors.lastname: Madrid
authors.forename: A
authors.initials: A
authors.lastname: Hameau
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Caminade
authors.forename: J P
authors.initials: JP
authors.lastname: Majoral
authors.forename: M A
authors.initials: MA
authors.lastname: Muñoz-Fernández
mesh_terms: D050091:Dendrimers / Q000008:administration & dosage* / Q000138:chemical synthesis; D015316:Genetic Therapy / Q000379:methods; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D050997:Nanomedicine / Q000379:methods; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000138:chemical synthesis; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000138:chemical synthesis; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection / Q000379:methods*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D050091:Dendrimers; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; D034741:RNA, Small Interfering; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1