Decoy oligodeoxynucleotides: A promising therapeutic strategy for inflammatory skin disorders

Hum Immunol. 2024 Nov;85(6):111161. doi: 10.1016/j.humimm.2024.111161. Epub 2024 Oct 24.

Abstract

Chronic inflammatory skin conditions such as psoriasis and atopic dermatitis (AD) impose a significant burden on both the skin and the overall well-being of individuals, leading to a diminished quality of life. Despite the use of conventional treatments like topical steroids, there remains a need for more effective and safer therapeutic options to improve the lives of patients with severe skin conditions. Molecular therapy has emerged as a promising approach to address disorders such as atopic dermatitis, psoriasis, and contact hypersensitivity. One strategy to counteract the disease processes involves targeting the transcriptional process. A novel form of gene therapy utilizes double-stranded oligodeoxynucleotides (ODNs), also known as decoys, that contain cis-elements. By introducing these decoy ODNs through transfection, the cis-trans interactions are disrupted, leading to the inhibition of trans-factors from binding to the intrinsic cis-elements and thus regulating gene expression. In this review, we have summarized studies investigating the therapeutic effects of decoy ODNs on inflammatory skin diseases. Various transcription factors, including NF-kB, STAT6, HIF-1α/STAT5, STAT1, and Smad, have been targeted and inhibited using designed decoy ODNs for the treatment of atopic dermatitis, psoriasis, hypertrophic scarring, and contact hypersensitivity. The findings of these studies confirm the significant potential of the decoy approach in the treatment of inflammatory skin diseases.

Keywords: Atopic dermatitis; Decoy; Inflammatory; Psoriasis; Skin diseases; Therapeutics.

Publication types

  • Review

MeSH terms

  • Animals
  • Dermatitis, Atopic* / drug therapy
  • Dermatitis, Atopic* / immunology
  • Dermatitis, Atopic* / therapy
  • Genetic Therapy / methods
  • Humans
  • Oligodeoxyribonucleotides* / therapeutic use
  • Psoriasis / drug therapy
  • Psoriasis / immunology
  • Psoriasis / therapy
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Oligodeoxyribonucleotides
  • Transcription Factors