Rethinking RNA Modifications: Therapeutic Strategies for Targeting Dysregulated RNA

Area of Science:

• Molecular Biology
• Epigenetics
• Drug Discovery

Background:

• Cellular ribonucleic acid (RNA) modifications regulate RNA stability, folding, localization, and translation accuracy.
• Mutations in RNA-modifying enzymes cause disease, while their dysregulation, particularly methyltransferases like METTL3, activates oncogenic pathways.
• Small molecule inhibitors targeting RNA-modifying enzymes are being developed for diseases, but potential off-target effects exist.

Purpose of the Study:

• To review current RNA-targeted therapies and their applications in various diseases.
• To explore advancements in oligonucleotide modalities and small molecules for RNA-targeted treatments.
• To identify knowledge gaps in epitranscriptome drug development for targeting mis-regulated RNA.

Main Methods:

• Literature review of RNA-targeted therapies.
• Analysis of small molecule inhibitors and oligonucleotide modalities.
• Examination of the role of RNA-modifying enzymes in disease.

Main Results:

• RNA-modifying enzymes play crucial roles in cellular processes beyond disease, including immunity and neural health.
• Targeting RNA substrates mis-regulated by abnormal RNA-modifying enzyme levels presents an alternative therapeutic strategy.
• Current therapies include oligonucleotide modalities and small molecules, with ongoing advancements.

Conclusions:

• Developing treatments that specifically target mis-regulated RNA substrates offers a novel approach to mitigate diseases driven by altered RNA-modifying enzyme levels.
• Further research is needed to address knowledge gaps in epitranscriptome drug development.
• RNA-targeted therapies hold significant potential for treating a range of diseases.