UC Irvine Scientists Unveil C28: A Novel DNA Polymerase Revolutionizing RNA Synthesis

Scientists at the University of California, Irvine (UC Irvine) have developed a novel DNA polymerase, named C28, capable of efficiently and accurately synthesizing RNA. This enzyme addresses long-standing challenges in the production of RNA molecules, which are integral to various biomedical applications including vaccines, diagnostics, and gene-based therapies. The groundbreaking research findings were published in Nature Chemical Biology.

C28 addresses long-standing challenges in RNA production, paving the way for advancements in vaccines, diagnostics, and gene therapies.

C28's Remarkable Capabilities

The C28 enzyme demonstrates several key capabilities, positioning it as a versatile tool for biotechnology:

• It produces RNA at speeds comparable to natural processes while maintaining high accuracy.
• It supports the synthesis of long RNA sequences.
• C28 can perform reverse transcription, converting RNA back into DNA.
• It enables the generation of hybrid DNA-RNA molecules using standard polymerase chain reaction (PCR) techniques.
• The enzyme readily incorporates chemically modified RNA building blocks, including those utilized in mRNA vaccines and other RNA-based therapeutics.

Developed Through Directed Evolution

The research team, led by UC Irvine professor of pharmaceutical sciences John Chaput, developed C28 through directed evolution, rather than manual engineering. This innovative process involved employing a high-throughput, single-cell screening platform to recombine related polymerase genes and test millions of enzyme variants. This methodology ultimately identified C28, which carries multiple mutations that collectively enable its efficient RNA synthesis capabilities.

C28 was discovered through a high-throughput, single-cell screening platform that tested millions of enzyme variants, demonstrating the profound power of directed evolution.

Broad Implications for Biomedical Innovation

The combination of speed, accuracy, and flexibility offered by C28 positions it as a significant new tool for researchers and biotechnology developers. It is particularly relevant for applications requiring customized or chemically modified RNA molecules. The study also highlights the capacity of directed evolution to create molecular functions not observed in nature, potentially advancing RNA biology, synthetic biology, and broader biomedical innovation.

C28's development underscores the power of directed evolution to create novel molecular functions, opening new avenues in RNA biology, synthetic biology, and biomedical innovation.

The study received support from the National Science Foundation.