Scientists at Scripps Research have built a tool that can speed up protein evolution by orders of magnitude β letting labs create and test new protein versions in days instead of months. The system, called T7-ORACLE, was reported in Science on August 7, 2025 and covered by ScienceDaily.
T7-ORACLE works by adding a second, independent DNA replication system inside E. coli cells. That orthogonal T7 replisome copies only specially designed plasmids, not the host genome, and the team made the T7 polymerase intentionally error-prone. The result: mutation rates on the target plasmid jump as much as 100,000-fold, producing huge numbers of variants each time the bacteria divide.
To show it works, the researchers put a common antibiotic-resistance gene (TEM-1 Ξ²-lactamase) into the system and exposed the bacteria to rising antibiotic doses. In under a week, the platform evolved enzyme versions that survived antibiotic levels thousands of times higher than the original. Many of the mutations matched resistance patterns seen in clinical settings β and some new combinations were even stronger.
Why this matters: labs can now combine rational design with nonstop evolution. Because T7-ORACLE uses standard E. coli workflows and common lab methods, it is relatively easy to adopt. That means faster development of therapeutic enzymes, better antibodies for cancer, and quicker ways to test how drug targets might evolve resistance. The authors also highlight future uses in synthetic genomics and evolving enzymes with novel chemistries.
T7-ORACLE is not a medicine by itself. It is a powerful research platform that shortens the path from idea to tested molecule. With careful oversight and ethical safeguards, it could help researchers stay ahead of disease and design better, faster therapies.
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