Scientists invent fast method for "directed evolution" of useful new molecules

Source: Xinhua| 2019-07-05 00:34:43|Editor: Wu Qin
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WASHINGTON, July 4 (Xinhua) -- Scientists in the United States created a powerful technique to "cultivate" new functional proteins in mammalian cells, and those proteins can be developed into potential treatment for various diseases including cancer.

The study published on Thursday in the journal Cell demonstrated the technique called "directed evolution" by evolving proteins to perform new tasks within days.

Directed evolution is an artificial, sped-up version of the evolution process in nature, which transforms a single DNA sequence into new therapeutics. But the existing methods, typically applied in bacterial cells, are laborious and time-consuming.

Researchers from University of North Carolina (UNC) School of Medicine developed a relatively quick, easy and versatile tool. They loaded the Sindbis virus with a genetic cargo to be modified, and the virus can infect cells in a culture dish and then mutate rapidly and precisely.

The mutant genes that thrive are those genes encoding proteins capable of accomplishing a desired function within the cells, such as activating a certain receptor, or switching on certain genes, according to the study.

The technique can evolve new human, mouse or other mammalian proteins that would be burdensome or impossible to generate with traditional bacterial cell-based methods, according to the researchers.

In one experiment, the researchers modified a protein that normally stops working if it encounters an antibiotic, but an evolved version with 22 mutations could keep working despite high dosage of the antibiotic.

The process took just seven days while a previously-reported mammalian directed evolution method took four months to yield only two mutations, said the paper's lead author Justin English, a postdoctoral research associate at UNC School of Medicine. "What we have developed is the most robust system yet for directed evolution in mammalian cells."

English's team also showed the tool's potential to guide drug development. They rapidly evolve small biological molecules called nanobodies that could activate different brain cell receptors that are targeted by many psychiatric drugs.

Now, they are working to engineer nanobodies that can neutralize cancer-causing genes.