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Directed evolution is a laboratory method that speeds up protein mutations to help create novel cancer and neurodegenerative disorder therapies. In a new study, scientists detail a method called T7-ORACLE, which makes this rapid evolution process faster and more effective. Researchers estimate that this method speeds up evolution some 100,000 times and allows scientists to introduce mutations in a matter of minutes rather than weeks.
All current life on Earth is the result of billions of years of slow, laborious, and endlessly fascinating evolution (if you include our time spent as single-celled microbes, of course). While that’s an acceptable timeline on geological scales, this rate of evolution isn’t going to cut it for biotechnology companies.
Instead, these companies rely on a technique known as directed evolution—the process of rapidly evolving proteins, introducing beneficial mutations, and selecting advantageous variants. While this can drastically speed up the clock (at least, compared to Mother Nature’s method of doing things), directed evolution can still be a pretty long process. And because these hyper-evolved proteins can be used in a wide variety of potential cancer and neurodegenerative therapies, we want this laboratory process to be as fast and as streamlined as possible.
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Luckily, scientists have been making some pretty astounding progress. In May of this year, a study led by the University of Sydney and published in Nature Communications detailed a process called PROTein Evolution Using Selection (PROTEUS) that leverages chimeric virus-like vesicles to rapidly evolve biomolecules. Now, a second study (led by Scripps Research and published in the journal Science) showcases yet another method for directed evolution called T7-ORACLE. According to the researchers, this breakthrough behaves like an “evolution engine” capable of introducing mutations 100,000 times faster than normal.
“This is like giving evolution a fast-forward button,” Pete Schultz, a co-senior author on the paper from Scripps Research, said in a press statement. “You can now evolve proteins continuously and precisely inside cells without damaging the cell’s genome or requiring labor-intensive steps.”
Schultz’s team circumvents typical directed evolution bottlenecks by engineering the bacterium and model organism E. coli to host what they call a “second, artificial DNA replication system derived from bacteriophage T7.” T7 phage is a virus that infects bacteria and has been widely studied, as it’s remarkably good at that particular job. This system is orthogonal, meaning it operates outside of the cell’s own biological machinery, and it also targets only plasmid DNA—small, circular DNA that replicates separate from a cell’s chromosomal DNA. Because the cell’s genome remains untouched, scientists can introduce mutations every time the cell divides (roughly every 20 minutes).
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“This system represents a major advance in continuous evolution,” Christian Diercks, another co-senior author of the study from Scripps Research, said in a press statement. “Instead of one round of evolution per week, you get a round each time the cell divides—so it really accelerates the process.”
To test this new platform, the team introduced TEM-1 β-lactamase—an antibiotic resistance gene—into the platform and exposed the E. coli bacterium to escalating levels of antibiotics. In less than a week, the system produced enzymes capable of withstanding antibiotics at levels 5,000 times higher than the original. So, not only can T7-Oracle be an important tool for developing new medicines, it could also give scientists a better understanding of how antibiotic resistance builds up over time. While a nice benefit, the paper’s authors are more interested in the therapeutic possibilities.
“What’s exciting is that it’s not limited to one disease or one kind of protein,’ Diercks said in a press statement. “What matters is that we can now evolve virtually any protein, like cancer drug targets and therapeutic enzymes, in days instead of months.”
Darren lives in Portland, has a cat, and writes/edits about sci-fi and how our world works. You can find his previous stuff at Gizmodo and Paste if you look hard enough.