A potent induction of naked/uridine-unmodified mRNA expression with Jet Injector, Actranza Lab in mouse and rat skins

Messenger RNA (mRNA) and plasmid DNA (pDNA) have emerged as pivotal platforms in genetic medicine, yet their effective intradermal (ID) delivery remains a major limitation. Here, we evaluated and compared gene transfer efficiency using a conventional 30-gauge needle syringe (30G-NS) and a needle-free jet-injector (Actranza Lab) in mouse and rat skin. Naked, uridine-unmodified luciferase (Luc) mRNA and Luc-encoding pDNA were administered at varying doses, and gene expression was quantified by luciferase assay. Dose-response studies revealed dramatically enhanced expression following Actranza jet injection compared with needle injection, with Luc mRNA expression elevating 100-200-fold in mice and 2,000-3,000-fold in rats. Time-course analysis demonstrated that Luc mRNA expression was detectable within 0.5 h, peaked between 5-8 h, and declined thereafter, while Luc pDNA exhibited delayed onset but prolonged expression, peaking at 16-24 h. Intriguingly, co-administration of mRNA and pDNA suppressed Luc expression compared with either nucleic acid alone, suggesting antagonistic rather than synergistic effects. These findings establish Actranza jet injection as a highly efficient approach for cutaneous nucleic acid delivery, significantly outperforming conventional needle injection. The distinct kinetics of mRNA versus pDNA emphasize their complementary yet mechanistically divergent expression profiles, while their unexpected interaction highlights the need for careful design of combination strategies. Collectively, our results underscore the transformative potential of jet-injector platforms for advancing genetic vaccination and therapy.