The emergence of RNA vaccines against SARS-CoV-2 has revolutionised the biomedical field, offering unprecedented flexibility, precision, and scalability in therapeutic development. Beyond addressing infectious diseases, RNA technology – including mRNA, self-amplifying RNA (saRNA), and circular RNA (circRNA) – is now being explored for applications in oncology, genetic disorders and autoimmune disease management.

This article gives an overview of the latest advancements in RNA vaccines against infectious diseases and cancer, including design and delivery systems, and highlights both opportunities and challenges in this rapidly evolving field.

Messenger RNA (mRNA): A linear RNA molecule where the sequence coding for the vaccine antigen is flanked by untranslated regions (UTRs), a 5′ methylguanylate cap and a 3′ polyadenylate (polyA) sequence, ensuring its stability and efficient translation in the cell.

Self-amplifying RNA (saRNA): A linear RNA molecule encoding for the vaccine antigen plus a viral replicase, composed of four non-structural proteins (nsPs). The replicase amplifies the RNA within the cell, thereby enhancing the antigen production.

Circular RNA (circRNA): A covalently closed-loop RNA molecule that lacks a 5′ cap and 3′ polyA tail, relying on an internal ribosome entry site (IRES) for translation of the vaccine antigen. Although the UTRs and 3′ polyA tail are not essential, they can enhance translation efficiency.