Scientists at the University of Sydney have developed PROTEUS, a bio-AI system that designs and evolves new functional molecules directly in mammalian cells, according to a breakthrough study in Nature Communications. The tool revolutionizes gene therapy and research tool development.
A collaboration between the university’s Charles Perkins Centre and the Centenary Institute, the research applies directed evolution to mammalian cells. PROTEUS (Protein Evolution Using Selection) simulates natural evolution, slashing evolutionary cycles from years or decades to weeks.
“This lets us create highly functional new molecules in humans, enabling drugs unachievable with current tech,” said co-author Professor Greg Neely. Unlike traditional bacterial-based directed evolution, PROTEUS works in mammalian cells, exploring millions of novel molecular sequences to solve specific problems—like shutting down disease-causing genes—delivering results in weeks.
“2018’s Nobel-winning bacterial directed evolution transformed biochemistry; PROTEUS takes this further, tackling genetic problems in mammalian cells,” noted lead researcher Dr. Christopher Denes. The system has already produced drug-responsive proteins and nanobodies detecting DNA damage (linked to cancer), with potential to enhance most proteins.
Key challenges—stabilizing cells during evolution and preventing “cheating”—were solved using chimeric virus-like particles, combining viral shells and genes to block shortcuts. This allows parallel testing of solutions, with effective ones prevailing.
“PROTEUS is validated as stable and reliable,” Denes said, adding it will be freely available to researchers to advance enzymes, molecular tools, and therapies—improving gene editing and mRNA drugs for better efficacy and specificity.
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