title: Enhanced antisense inhibition of human immunodeficiency virus type 1 in cell cultures by DLS delivery system.
abstract: The relatively poor cell uptake of oligonucleotides and subsequent transport to the cytoplasm and nucleus is the main limitation in antisense therapeutics. The use of lipid-based carrier system is one of the most promising approaches to overcome these problems. In this study, we report the use of a new lipidic formulation to deliver a phosphorothioate oligonucleotide antisense directed against the regulatory gene rev of the HIV-1 genome and its application to the inhibition of HIV-1 in different cell culture models. Antiviral activity of either DLS-complexed or non-complexed oligonucleotides (ODNs) was compared in acutely and chronically infected cells. We have demonstrated that substantial antisense activity could be achieved at subnanomolar concentrations with DLS-complexed ODN in both acute and chronic infection systems. DLS-association highly improved inhibitory activity of the antisense ODN in acutely infected Molt-3 cells (100-fold) and primary cells (1000-fold) and in chronically infected H9 cells (1,500,000-fold). We have shown that anti-HIV activity of phosphorothioate ODNs can be strongly enhanced by using the DLS carrier system.
authors.affiliation: Département de Microbiologie et Immunologie, Faculté de Médecine, Université de Montréal, Québec, Canada. carole.lavigne@sympatico.ca
authors.forename: C
authors.initials: C
authors.lastname: Lavigne
authors.forename: A R
authors.initials: AR
authors.lastname: Thierry
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D015757:Genes, rev; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008081:Liposomes; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D008081:Liposomes; D016376:Oligonucleotides, Antisense