CJ-1: an optimized mRNA platform with enhanced protein expression and minimal immunogenicity for therapeutic...

Messenger RNA therapeutics offer broad potential across various diseases, yet achieving sustained and efficient protein expression remains a central challenge. In this study, we report CJ-1, a novel mRNA construct engineered through systematic optimization of major regulatory elements, including the 5' and 3' untranslated regions and poly (A) tail. CJ-1 consistently outperformed first-generation mRNA constructs in protein expression across multiple cell types and in vivo mouse models. Moreover, CJ-1 elicited markedly lower cytokine responses, indicating reduced innate immune activation. To evaluate its therapeutic applicability, erythropoietin (EPO)-encoding CJ-1 mRNA was encapsulated in a Pfizer-BioNTech lipid nanoparticle formulation and administered intraperitoneally in mice. This resulted in elevated, sustained serum EPO levels and significant increases in reticulocyte counts and hematocrit. These findings support CJ-1 as a promising mRNA platform with enhanced expression and minimal immunogenicity, advancing the development of safer and more effective mRNA-based therapies.