RNA-based drugs: current, imminent and possible therapeutic applications

Abstract

In a relatively brief period, the mRNA COVID-19 vaccines have saved millions of lives and have considerably contributed to return to normality after the pandemic. More broadly, the development of RNA-based drugs represents a real paradigm shift with promising therapeutic applications. Besides their safety and efficacy, RNA-based drugs are essentially easy to design and manufactured and may therefore be cost effective. At the pharmacological level, the development of RNA-based drugs marks a breakthrough because these drugs can reach previously "undruggable" pharmacological targets. This clearly represents a step toward the possible establishment of personalized treatments for several difficult-to-treat diseases. This review provides an updated, critical, and comprehensive pharmacological analysis of the current RNA therapeutics landscape, including both approved RNA-based drugs and key investigational candidates. We summarize the state of clinical progress, highlighting pharmacological mechanisms, challenges in drug delivery, tolerability, and clinical outcomes. Our comprehensive overview emphasizes the versatility of RNA-based drugs, illustrating their therapeutic application across various diseases such as cancer, neurodegenerative, cardiovascular, metabolic, rare genetic, and infectious diseases. Also, we uniquely explore the concept of RNA-based drugs repurposing, which may leverage shared pathophysiological mechanisms across diseases to accelerate clinical impact.

Keywords: ASO; Aptamer; Cancer; Therapy; mRNA vaccine; miRNA; siRNA.