IntroductionThe mRNA platform has revolutionised vaccine technology by offering a universal, rapid, and easily scalable production process. Two main types of mRNA vectors exist—linear (cap‑dependent) and circular (cap‑independent)—each with distinct advantages.
Although both vector types are continuously being improved, a comprehensive comparative analysis of the most efficient existing vectors of each type has been lacking.MethodsWe compared the expression efficiency, protective activity, and therapeutic activity of circular and linear mRNA vectors. Linear vectors were tested in different configurations: containing either N1‑methylpseudouridine or uridine, and capped with either ARCA (m7G(5′)ppp(5′)G) or CleanCap (m7G(5′)ppp(5′)m2G).
Circular vectors contained either the commonly used IRES of coxsackievirus B3 or a new IRES of human rhinovirus B6. Expression levels were evaluated using a luciferase reporter assay and target protein expression.
Protective activity was assessed through both active immunization (immunogenicity and subsequent SARS-Cov2 challenge) and passive immunization (recombinant antibody production and toxin challenge).ResultsPreliminary luciferase assays showed that modified linear vectors achieved significantly higher expression levels both in vitro and in vivo. A similar, though less pronounced, difference was observed for target protein expression.
Frontiers in Immunology published a clinical update in Infectious Disease on 24 Apr 2026.
The item focuses on Circular mRNA against CleanCap linear mRNA vectors: comprehensive comparison, expression, active and passive immunization.
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