A Decoy Oligodeoxynucleotides therapy for allergic skin diseases

Abstract

Atopic dermatitis (AD) is a common, chronically relapsing skin disease. It is very difficult to treat severe type AD by steroid ointment. We therefore hypothesized that synthetic double-stranded DNA with a high affinity for Signal Transducers and Activators of Transcription 6 (STAT6) could be introduced in vivo as a decoy cis elements to bind the transcriptional factor and to block the gene activation of contributing the onset and progression of AD, thus providing effective therapy for AD. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODN), but not scrambled decoy ODN in the AD model mice, had a significantly inhibitory effect on not only STAT6 binding to nuclei but also on the third phase response. A histological analysis revealed that both edema and the infiltration of eosinophils and degranulated mast cells significantly decreased in STAT6 decoy ODN transfected mice. We herein report the first successful in vivo transfer of STAT6 decoy ODN to reduce the third phase reaction in AD model mice, thereby providing a new therapeutic strategy for atopic dermatitis. We also introduce another NF-kB Decoy Oligodeoxynucleotides therapy or STAT6siRNA therapy for allergic diseases.