Scripps Scientists build an “evolution engine” to rapidly reprogram proteins

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On Aug. 7, 2025, research scientists at Scripps Research announced a new platform that enables fast, scalable protein evolution—opening the door to new therapies and diagnostics, and to predicting resistance mutations across many disease areas.

In medicine and biotechnology, the ability to evolve proteins with new or improved functions is crucial, but current methods are often slow and laborious. Now, Scripps Research scientists have developed a synthetic biology platform that accelerates evolution itself—enabling researchers to evolve proteins with useful, new properties thousands of times faster than nature. The system, named T7-ORACLE, was described in Science, and represents a breakthrough in how researchers can engineer therapeutic proteins for cancer, neurodegeneration and essentially any other disease area.

Directed evolution is a laboratory process that involves introducing mutations and selecting variants with improved function over multiple cycles. It’s used to tailor proteins with desired properties, such as highly selective, high-affinity antibodies, enzymes with new specificities or catalytic properties, or to investigate the emergence of resistance mutations in drug targets. However, traditional methods often require repeated rounds of DNA manipulation and testing with each round taking a week or more. Systems for continuous evolution—where proteins evolve inside living cells without manual intervention—aim to streamline this process by enabling simultaneous mutation and selection with each round of cell division (roughly 20 minutes for bacteria). But existing approaches have been limited by technical complexity or modest mutation rates.

To demonstrate the power of T7-ORACLE, the research team inserted a common antibiotic resistance gene, TEM-1 β-lactamase, into the system and exposed the E. coli cells to escalating doses of various antibiotics. In less than a week, the system evolved versions of the enzyme that could resist antibiotic levels up to 5,000 times higher than the original. This proof-of-concept demonstrated not only T7-ORACLE’s speed and precision, but also its real-world relevance by replicating how resistance develops in response to antibiotics.

This could help scientists more rapidly evolve antibodies to target specific cancers, evolve more effective therapeutic enzymes, and design proteases that target proteins involved in cancer and neurodegenerative disease.

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Source: Scripps Research
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