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Modulating the expression of tumor suppressor genes using activating oligonucleotide technologies as a therapeutic

Georgina L Gregory1, Ian M Copple1

  • 1Department of Pharmacology & Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK.

Molecular Therapy. Nucleic Acids
|January 26, 2023
PubMed

Insights

Tumor suppressor genes (TSGs) are often lost in cancer. Activating oligonucleotide therapies, like small-activating RNAs and synthetic mRNAs, offer new ways to restore TSG expression and combat cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Therapy

Background:

  • Tumor suppressor genes (TSGs) are critical for preventing cancer but are frequently downregulated in malignant cells.
  • Epigenetic modifications and copy number alterations can subtly decrease TSG expression, leading to functional loss and cancer progression.
  • Restoring normal TSG expression presents a therapeutic opportunity.

Purpose of the Study:

  • To review activating oligonucleotide therapies as a novel strategy to increase TSG expression in cancer.
  • To explore the potential of small-activating RNAs and synthetic messenger RNAs (mRNAs) in cancer treatment.

Main Methods:

  • This review focuses on oligonucleotide-based therapeutic approaches.
  • The study examines small-activating RNAs (saRNAs) and synthetic mRNAs as methods to upregulate TSGs.
  • The continuum model of tumor suppression is discussed as a framework for understanding TSG function.

Main Results:

  • Oligonucleotide therapies can modulate endogenous gene expression by introducing exogenous nucleic acids.
  • Small-activating RNAs and synthetic mRNAs are identified as promising tools for restoring TSG levels.
  • These therapies aim to counteract the effects of TSG downregulation in cancer.

Conclusions:

  • Activating oligonucleotide therapies represent a novel therapeutic avenue for cancer treatment.
  • Restoring tumor suppressor gene expression is a viable strategy to combat cancer.
  • Small-activating RNAs and synthetic mRNAs hold significant potential for future cancer therapies.
Keywords:
MT: oligonucleotides: therapies and applicationscancermRNAoligonucleotidesaRNAtumor suppressor gene

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