Programmable RNA Editing via Adenosine Deaminase Acting on RNA Enzymes: Current Advances and Clinical Potential

Adenosine deaminase acting on RNA (ADAR)-mediated RNA editing has emerged as a powerful and precise technology for modifying RNA transcripts, enabling correction of disease-causing mutations without permanent changes to the genome. Recent advances in ADAR protein engineering, guide RNA design, and delivery methods have significantly improved editing efficiency and specificity, overcoming many initial limitations. These developments have expanded the therapeutic potential of ADAR-based editing across a range of conditions, including genetic disorders, cancer, metabolic diseases, and neurodegenerative disorders. Notably, several ADAR-based therapeutics have now entered early clinical trials, marking a critical milestone in translating this technology from bench to bedside. Moreover, its inherent programmability, reversibility, and transient nature make ADAR-mediated RNA editing a highly attractive platform for personalized medicine, enabling tailored interventions based on individual genetic profiles and disease contexts. This review provides a comprehensive comparison of recent innovative advancements in ADAR-based RNA editing technologies, their use in diverse contexts pertinent to human diseases, the key challenges that remain, and future directions for their therapeutic implementation.