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Scripps Research Develops T7-ORACLE to Accelerate Protein Evolution for Therapeutic Applications

WHAT'S THE STORY?

What's Happening?

Researchers at Scripps Research Institute have developed a synthetic biology platform named T7-ORACLE, which significantly accelerates the evolution of proteins for therapeutic applications. This platform allows proteins to evolve thousands of times faster than natural processes, enabling continuous and precise evolution inside cells without damaging the cell's genome. The system uses E. coli bacteria engineered to host a second artificial DNA replication system derived from bacteriophage T7. This method introduces mutations into target genes at a rate 100,000 times higher than normal, facilitating rapid evolution of proteins. The research team demonstrated the system's effectiveness by evolving antibiotic resistance genes in E. coli, achieving resistance levels up to 5,000 times higher than the original. The platform is expected to have broad applications in cancer, neurodegeneration, and other therapeutic areas.
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Why It's Important?

The development of T7-ORACLE represents a significant advancement in the field of synthetic biology and protein engineering. By accelerating protein evolution, this platform could lead to the creation of more effective therapeutic proteins, potentially transforming treatments for various diseases. The ability to rapidly evolve proteins could also enhance research into drug resistance, providing insights into how resistance mutations develop and how they can be countered. This technology may benefit pharmaceutical companies and researchers by streamlining the development of new drugs and therapies, potentially reducing costs and time associated with traditional methods.

What's Next?

The research team plans to focus on evolving human-derived enzymes for therapeutic use and tailoring proteases to recognize specific cancer-related protein sequences. Future studies may explore the evolution of polymerases that can replicate entirely unnatural nucleic acids, opening possibilities in synthetic genomics. The platform's generalizability suggests it could be applied to a wide range of protein engineering challenges, potentially leading to breakthroughs in drug development and other biotechnological applications.

Beyond the Headlines

The T7-ORACLE system reflects a broader synthetic biology goal of rebuilding key biological processes to function independently of host cells. This separation allows scientists to reprogram these processes without disrupting normal cellular activity, potentially leading to new approaches in genetic engineering and biotechnology. The platform's ability to evolve proteins rapidly and precisely could also have implications for understanding evolutionary processes and developing novel biomaterials.

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