Delivery of antisense peptide nucleic acids (PNAs) to the cytosol by disulphide conjugation to a lipophilic cation

FEBS Lett. 2004 Jan 2;556(1-3):180-6. doi: 10.1016/s0014-5793(03)01403-0.

Abstract

Peptide nucleic acids (PNAs) are effective antisense reagents that bind specific mRNAs preventing their translation. However, PNAs cannot cross cell membranes, hampering delivery to cells. To overcome this problem we made PNAs membrane-permeant by conjugation to the lipophilic triphenylphosphonium (TPP) cation through a disulphide bond. The TPP cation led to efficient PNA uptake into the cytoplasm where the disulphide bond was reduced, releasing the antisense PNA to block expression of its target gene. This method of directing PNAs into cells is a significant improvement on current procedures and will facilitate in vitro and pharmacological applications of PNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antisense Elements (Genetics) / metabolism*
  • Base Sequence
  • Cations
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • Disulfides / chemistry*
  • Humans
  • Leukemia P388
  • Mice
  • Organophosphorus Compounds / chemistry
  • Peptide Nucleic Acids / chemistry*
  • Peptide Nucleic Acids / genetics
  • Peptide Nucleic Acids / metabolism*

Substances

  • Antisense Elements (Genetics)
  • Cations
  • Disulfides
  • Organophosphorus Compounds
  • Peptide Nucleic Acids
  • thiobutyltriphenylphosphonium