Enhanced antisense inhibition of human immunodeficiency virus type 1 in cell cultures by DLS delivery system

Biochem Biophys Res Commun. 1997 Aug 28;237(3):566-71. doi: 10.1006/bbrc.1997.7191.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Carriers
  • Genes, rev
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Liposomes
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / pharmacology*
  • Time Factors
  • Virus Replication / drug effects*

Substances

  • Anti-HIV Agents
  • Drug Carriers
  • Liposomes
  • Oligonucleotides, Antisense