Emerging Nucleic Acid Cargos for Next-Generation RNA Vaccines and Therapeutics

Messenger RNA (mRNA) lipid nanoparticles (LNPs) have emerged as a transformative technology with broad applications in vaccines, protein replacement therapy, and gene editing. However, the transient nature of mRNA expression often necessitates high or repeated dosing regimens, limiting its therapeutic potential. Thus, there is a critical need for innovation at the interface of RNA biology and drug delivery that prolong the duration of RNA translation. In this Viewpoint, we provide an overview of emerging nucleic acid cargos that address these challenges, specifically self-amplifying RNA (saRNA) and circular RNA (circRNA), and provide a framework for how these nucleic acid cargos can enable the next generation of vaccines and therapeutics for diverse clinical applications.