Clinical delivery of circular RNA: Lessons learned from RNA drug development

Abstract

Circular RNAs (circRNA) represent a distinct class of covalently closed-loop RNA molecules, which play diverse roles in regulating biological processes and disease states. The enhanced stability of synthetic circRNAs compared to their linear counterparts has recently garnered considerable research interest, paving the way for new therapeutic applications. While clinical circRNA technology is still in its early stages, significant advancements in mRNA technology offer valuable insights into its potential future applications. Two primary obstacles that must be addressed are the development of efficient production methods and the optimization of delivery systems. To expedite progress in this area, this review aims to provide an overview of the current state of knowledge on circRNA structure and function, outline recent techniques for synthesizing circRNAs, highlight key delivery strategies and applications, and discuss the current challenges and future prospects in the field of circRNA-based therapeutics.

Keywords: Drug delivery; Lipid nanoparticles; Non-viral delivery; RNA therapeutics; circular RNA; mRNA.