Rapid Genetic Alteration: New "Evolution Engine" Speeds Up Gene Mutation by a Hundred-Thousand Fold Compared to Standard Processes
In a groundbreaking development, a team from the Scripps Research Institute has unveiled T7-ORACLE, an "evolution engine" designed to supercharge protein development inside living cells [1][2][3]. This innovative system, which can evolve various proteins such as cancer drug targets and therapeutic enzymes in days instead of months, promises broad utility for engineering improved therapeutic proteins across diverse conditions, including infections, cancers, and neurodegenerative disorders.
T7-ORACLE operates by introducing an artificial DNA replication system into E. coli bacteria, a widely used organism for protein production due to its ease of growth and rapid multiplication [4]. This orthogonal (independent) replication system hypermutates plasmid DNA at rates up to 100,000 times higher than natural mutation rates, without harming the bacterial genome [1]. This enables continuous, rapid cycles of mutation and selection every bacterial cell division, significantly reducing protein evolution times from weeks or months down to days.
The system works through a virus-derived T7 replisome that replicates plasmid DNA independently, focusing mutations specifically on target genes while preserving cell viability. This design allows fast, high-throughput directed evolution entirely inside living cells, avoiding the traditional labor-intensive, iterative DNA manipulation and screening processes [1][2].
Pete Schultz, the President and CEO of Scripps Research, described T7-ORACLE as giving evolution a "fast-forward button" [5]. The evolution of proteins can now occur in a lab, providing a powerful tool for researchers seeking to develop new drugs and therapies for complex diseases like cancer and neurodegeneration.
One potential application of T7-ORACLE is in the rapid evolution of proteins related to cancer drug targets, enabling quicker discovery and optimization of therapeutic enzymes or inhibitors that might overcome drug resistance or enhance efficacy [2][3]. In neurodegenerative diseases, T7-ORACLE could accelerate development of novel treatments that modify disease-related proteins or pathways [3].
The "evolution engine" is easy to set up and requires minimal adjustments for those who work with E. coli, making it accessible to a wide range of researchers [6]. Moreover, T7-ORACLE does not affect the host cell, ensuring the integrity of the evolved proteins [7].
The study involving T7-ORACLE has been published in the prestigious journal Science, further highlighting its potential impact on the field of protein engineering [8]. The team tested T7-ORACLE with a gene encoding an antibiotic-resistant protein, demonstrating its ability to evolve proteins to handle antibiotic doses up to 5,000 times higher than the initial dose, in less than a week [1].
In summary, T7-ORACLE supercharges continuous protein evolution inside living cells by harnessing a specialized, orthogonal replication system to rapidly generate and select beneficial mutations, significantly speeding up protein engineering. Its medical applications are especially promising for rapid development of new drugs and therapies in complex diseases like cancer and neurodegeneration.
- The evolution of proteins, such as cancer drug targets and therapeutic enzymes, can now be accelerated with T7-ORACLE, an "evolution engine" designed to operate inside living cells.
- T7-ORACLE can potentially evolve proteins related to cancer drug targets, enabling quicker discovery and optimization of therapeutic enzymes or inhibitors that might overcome drug resistance or enhance efficacy.
- In neurological disorders, T7-ORACLE could accelerate the development of novel treatments that modify disease-related proteins or pathways.
- The study of T7-ORACLE, published in the prestigious journal Science, highlights its potential impact on protein engineering, healthcare, and wellness, particularly in the development of new drugs and therapies for complex diseases like cancer and neurodegeneration.
- T7-ORACLE, which operates by introducing an artificial DNA replication system into E. coli bacteria, promises broad utility for engineering improved therapeutic proteins across diverse medical-conditions, including infections, cancers, and neurodegenerative disorders.
