Decoy oligodeoxynucleotides targeting STATs in non-cancer gene therapy

Gene. 2025 Jul 15:957:149482. doi: 10.1016/j.gene.2025.149482. Epub 2025 Apr 9.

Abstract

The Signal Transducer and Activator of Transcription (STAT) protein family is crucial for organizing the epigenetic configuration of immune cells and controlling various fundamental cell physiological functions including apoptosis, development, inflammation, immunological responses, and cell proliferation and differentiation. The human genome has seven known STAT genes, named 1, 2, 3, 4, 5a, 5b, and 6. Aberrant activation of STAT signaling pathways is associated with many human disorders, particularly cardiovascular diseases (CVDs), making these proteins promising therapeutic targets. Improved understanding of altered and pathological gene expression and its role in the pathophysiology of various hereditary and acquired disorders has enabled the development of novel treatment approaches based on gene expression modulation. One such promising development is the oligodeoxynucleotide decoy method, which may allow researchers to specifically influence gene activation or repression. Various oligodeoxynucleotide decoys target STATs and affect the expression of its downstream genes. We summarized cell culture and preclinical research, which evaluated the effects of oligodeoxynucleotide decoys target STATs in different types of non-cancer illnesses.

Keywords: Cell processes; Decoy oligodeoxynucleotides; STAT; STAT3; Signal transducer.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases* / genetics
  • Cardiovascular Diseases* / therapy
  • Gene Expression Regulation
  • Genetic Therapy* / methods
  • Humans
  • Oligodeoxyribonucleotides* / genetics
  • Oligodeoxyribonucleotides* / therapeutic use
  • STAT Transcription Factors* / antagonists & inhibitors
  • STAT Transcription Factors* / genetics
  • STAT Transcription Factors* / metabolism
  • Signal Transduction

Substances

  • STAT Transcription Factors
  • Oligodeoxyribonucleotides