Validation of a Generation 4 Phosphorus-Containing Polycationic Dendrimer for Gene Delivery Against HIV-1

Author(s): V. Briz, M.J. Serramia, R. Madrid, A. Hameau, Anne-Marie Caminade, J.P. Majoral, M.A. Munoz-Fernandez.

Journal Name: Current Medicinal Chemistry

Volume 19 , Issue 29 , 2012

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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.

Keywords: Nanomedicine, phosphorus dendrimer, HIV, oligodeoxynucleotides, siRNA and gene therapy

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Article Details

VOLUME: 19
ISSUE: 29
Year: 2012
Page: [5044 - 5051]
Pages: 8
DOI: 10.2174/0929867311209025044
Price: $58

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