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

TitleDelivery of antisense peptide nucleic acids (PNAs) to the cytosol by disulphide conjugation to a lipophilic cation.
Publication TypeJournal Article
Year of Publication2004
AuthorsFilipovska, A, Eccles, MR, Smith, RAJ, Murphy, MP
JournalFEBS Lett
Volume556
Issue1-3
Pagination180-6
Date Published2004 Jan 02
ISSN0014-5793
KeywordsAnimals, Antisense Elements (Genetics), Base Sequence, Cations, Cell Line, Tumor, Cell Membrane, Cytosol, Disulfides, Humans, Leukemia P388, Mice, Organophosphorus Compounds, Peptide Nucleic Acids
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.

DOI10.1016/s0014-5793(03)01403-0
Alternate JournalFEBS Lett.
Citation Key10.1016/s0014-5793(03)01403-0
PubMed ID14706847