Versatile Enzyme that Quickly, Accurately Synthesizes RNA Can Also Perform Reverse Transcription

Why It Matters

C28 streamlines the production of high‑quality RNA, accelerating the pipeline for mRNA vaccines, diagnostics, and synthetic‑biology applications, while showcasing directed evolution’s power to create new enzymatic functions.

Key Takeaways

• C28 polymerase synthesizes RNA at near‑natural speed
• Engineered via directed evolution, dozens of mutations across protein
• Performs reverse transcription and hybrid DNA‑RNA PCR
• Accepts chemically modified nucleotides used in mRNA vaccines
• Enables rapid, accurate production of custom RNA for therapeutics

Pulse Analysis

RNA has become a cornerstone of modern biomedicine, from mRNA vaccines to gene‑editing tools, yet manufacturing high‑fidelity RNA at scale remains a bottleneck. Traditional DNA polymerases reject ribonucleotides, forcing researchers to rely on multi‑step in vitro transcription processes that are time‑consuming and prone to errors. The emergence of a dedicated RNA‑synthesizing enzyme could dramatically reduce turnaround times, lower costs, and improve the consistency of therapeutic RNA batches, addressing a critical need across the biotech sector.

The UC Irvine team’s C28 polymerase was born from a high‑throughput directed‑evolution platform that shuffled related polymerase genes and screened millions of variants in single cells. After only a few selection cycles, C28 emerged with a constellation of mutations that collectively reshape the active site and substrate channel, enabling rapid incorporation of ribonucleotides without sacrificing accuracy. Remarkably, the enzyme also reverses the flow of information, copying RNA back into DNA, and tolerates a range of modified nucleotides essential for stabilizing mRNA vaccines and therapeutic RNAs. This multifunctionality consolidates several workflow steps into a single enzymatic reaction.

For industry, C28 offers a plug‑and‑play solution that can be integrated into existing PCR and synthetic‑biology pipelines, accelerating the design‑build‑test cycle for RNA therapeutics and diagnostics. Its ability to handle chemically altered bases opens doors for next‑generation vaccines with enhanced stability and reduced immunogenicity. Moreover, the success of C28 underscores the broader potential of directed evolution to generate bespoke enzymes, suggesting a future where custom biocatalysts are routinely engineered for specific molecular tasks, reshaping the landscape of molecular manufacturing.