Cold-adapted RNA polymerase from Pseudomonas phage Njord improves synthesis of therapeutic mRNA

Abstract

Significance Bacteriophage T7 RNA polymerase (T7 RNAP) has enabled the development of mRNA vaccines and remains central to the manufacture of this therapeutic modality. Here, we report on a natural homolog of T7 RNA polymerase, Njord RNA polymerase, which supports high-yield RNA synthesis at substantially lower temperatures. Njord RNAP generates mRNA with markedly reduced levels of inflammatory RNA contaminants, and comparative analysis of transcription reactions provides insight into the origins of these impurity species. Together, these features position Njord RNA polymerase as a valuable tool for low-temperature RNA synthesis and a promising candidate for improving the performance and scalability of mRNA therapeutics.