Targeting RNA adenosine editing and modification enzymes for RNA therapeutics

Vlachogiannis, Nikolas I.; Polycarpou-Schwarz, Maria; Avdi, Aikaterini-Paraskevi; Tual-Chalot, Simon; Stellos, Konstantinos

Targeting RNA adenosine editing and modification enzymes for RNA therapeutics

Tools

Preview	PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader 5MB
	Other (Supplemental Information) 726kB

Item Type:	Review
Title:	Targeting RNA adenosine editing and modification enzymes for RNA therapeutics
Creators Name:	Vlachogiannis, Nikolas I., Polycarpou-Schwarz, Maria, Avdi, Aikaterini-Paraskevi, Tual-Chalot, Simon and Stellos, Konstantinos
Abstract:	Adenosine-to-inosine (A-to-I) RNA editing, and N6 methyladenosine (m6A) are among the most abundant modifications in eukaryotic messenger RNA, affecting various aspects of RNA metabolism and cellular function, including proliferation, differentiation, responses to stressors, and cell death. Recent preclinical evidence suggests that both modifications play a significant role in multiple disorders, including infections, chronic inflammatory diseases, and cancer, sparking great interest in their therapeutic potential. Structural characterization of ADARs (adenosine deaminases acting on RNA) and key m6A enzymes has enabled the development of small molecule inhibitors modulating their expression, enzymatic activity, or binding to target RNAs. Herein, we review preclinical evidence supporting the therapeutic benefits of targeting ADARs and m6A enzymes in diverse disease contexts. Small molecule inhibitors of RNA modification enzymes have shown potent anti-proliferative and pro-apoptotic effects in cancer cells, and have successfully inhibited tumor growth in vivo, without evident toxicity, while their combination with immuno-/chemotherapeutics displayed synergistic anti-neoplastic action. Adenosine RNA editing via recruitment of endogenous ADARs and usage of guide RNAs showed remarkable efficacy in correcting G-to-A point mutations and restoring the associated protein expression with limited off-target activity. Future studies are warranted to evaluate the safety and clinical efficacy of RNA editing or modification-targeting therapeutics in patients.
Keywords:	Adenosine Deaminase, Adenosine, Neoplasms, RNA Editing, Animals
Source:	Molecular Therapy
ISSN:	1525-0016
Publisher:	Elsevier / Cell Press
Volume:	33
Number:	9
Page Range:	4044-4090
Date:	3 September 2025
Official Publication:	https://doi.org/10.1016/j.ymthe.2025.05.021
PubMed:	View item in PubMed

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year