C-5 propyne-modified oligonucleotides penetrate the epidermis in psoriatic and not normal human skin after topical application

Paul J. White, Andrew C. Gray, Rhys Fogarty, Rodney D. Sinclair, Susan P. Thumiger, George A. Werther, Christopher J. Wraight

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We have previously shown that antisense oligonucleotides effectively reduced insulin-like growth factor I receptor expression in human psoriatic skin grafted on to nude mice when injected intradermally. We therefore investigated the penetration of C-5 propyne modified antisense oligonucleotides into human normal and psoriatic skin after topical administration. Oligonucleotide (37.5 μg; 250 μM) was applied in aqueous solution or 5% methylcellulose gel for 24 h, prior to live confocal microscopy and fluorescence microscopy of fixed sections. We found that oligonucleotide could penetrate through the stratum corneum of psoriatic but not normal human skin over large regions of the epidermis. The oligonucleotide was localized to the nucleus of large parakeratotic cells in the psoriatic skin as well as smaller basal and suprabasal keratinocytes. In normal human skin, oligonucleotide was confined to the stratum corneum, with little or no oligonucleotide apparent in the viable epidermis. Electrophoresis of oligonucleotide recovered from treated psoriatic and normal skin revealed that the oligonucleotide remained intact over the 24 h period. In summary, we found that C-5 propyne modified antisense oligonucleotides could reach the target cells (in this case basal keratinocytes) after topical administration to psoriatic but not normal skin.

Original languageEnglish
Pages (from-to)1003-1007
Number of pages5
JournalJournal of Investigative Dermatology
Volume118
Issue number6
DOIs
Publication statusPublished - 1 Jan 2002

Keywords

  • Antisense oligonucleotide
  • Psoriasis
  • Topical delivery

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this