A two step model aimed at delivering antisense oligonucleotides in targeted cells

J. Toth, I. Boszormenyi, Z. S. Majer, I. Laczko, C. Malvy, M. Hollosi, J. R. Bertrand

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

To be efficient in vivo antisense oligonucleotides must reach the targeted cells and then cross the cellular membrane. We propose a two step system where the oligonucleotide is first electrostatically bound to a peptide coupled to a ligand of a cellular receptor. A complex is formed which allows the oligonucleotide to be bound to the membrane of the targeted cells. These oligonucleotides are then delivered inside the cells by the subsequent use of a transfection agent. As a reductionist model of peptide coupled to a ligand we have used a lipopeptide and characterized by a filter elution assay the stoichiometry between the peptide and the oligonucleotide in the complexes. Using HeLa cultured cells we have shown that addition of these complexes to the cells triggers the oligonucleotide binding to the cell membrane. The subsequent addition of dendrimers allows these antisense oligonucleotides to inhibit a reporter gene inside the cells.

Original languageEnglish
Pages (from-to)18-22
Number of pages5
JournalBiochemical and biophysical research communications
Volume293
Issue number1
DOIs
Publication statusPublished - Jan 1 2002

Keywords

  • Antisense oligonucleotide
  • Cell targeting
  • Delivery
  • Lipopeptide

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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