Proceedings of the National Academy of Sciences of the United States of AmericaSep 2, 2026

Cold-adapted RNA enzyme from Pseudomonas virus improves production of therapeutic mRNA

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Updated Sep 3, 2026

Abstract

Njord RNA polymerase can synthesize mRNA with minimal contamination from double-stranded RNA.

Njord RNAP transcribes RNA at high yield even at low temperatures.
The enzyme shows high transcriptional fidelity and promoter specificity.
DNA-templated promoter-independent transcription is a significant source of dsRNA impurities.
Njord RNAP demonstrates minimal activity that leads to dsRNA production.
mRNA synthesized with Njord RNAP elicits only a minimal immune response in cell culture and live animal studies.
The enzyme's efficiency and purity may enhance mRNA manufacturing processes.

Simplified

An RNA polymerase identified in the genome of Pseudomonas phage Njord offers a promising tool for the synthesis of mRNA and other therapeutic nucleic acids. Originating from a marine microbial ecosystem, Njord RNAP transcribes RNA at high yield even under low temperature conditions. Key properties of the enzyme relevant to mRNA synthesis are presented including transcriptional fidelity, promoter specificity, incorporation of modified nucleotides, and the impurity profile of the RNA. Specific attention is given to the formation of contaminating double-stranded RNA (dsRNA) species. Analysis of transcription reactions shows that DNA-templated promoter-independent transcription is a major source of detectable dsRNA impurities and that Njord RNAP displays a minimal level of this activity. Consistent with the known inflammatory role of dsRNA in synthetic mRNA, transcriptomic analysis of cell culture and a live animal study demonstrates that mRNA synthesized with Njord RNAP elicits only a minimal immune response. This natural enzyme enables efficient mRNA synthesis at ambient temperature and produces transcripts essentially free of dsRNA, offering significant potential to streamline mRNA manufacturing processes.

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mRNA TechnologyIssue #53

A cold-adapted viral enzyme makes cleaner mRNA with almost no inflammatory byproduct

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Cold-adapted RNA enzyme from Pseudomonas virus improves production of therapeutic mRNA

Abstract

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