“The invention of directed evolution changed the trajectory of biochemistry. Now, with PROTEUS, we can program a mammalian cell with a genetic problem we aren’t sure how to solve. Letting our system run continuously means we can check in regularly to understand just how the system is solving our genetic challenge,” said lead researcher Dr Christopher Denes from the Charles Perkins Centre and School of Life and Environmental Sciences

The biggest challenge Dr Denes and the team faced was how to make sure the mammalian cell could withstand the multiple cycles of evolution and mutations and remain stable, without the system “cheating” and coming up with a trivial solution that doesn’t answer the intended question.

They found the key was using chimeric virus-like particles, a design consisting of taking the outside shell of one virus and combining it with the genes of another virus, which blocked the system from cheating.

The design used parts of two significantly different virus families creating the best of both worlds. The resulting system allowed the cells to process many different possible solutions in parallel, with improved solutions winning and becoming more dominant while incorrect solutions instead disappear.

“PROTEUS is stable, robust and has been validated by independent labs. We welcome other labs to adopt this technique. By applying PROTEUS, we hope to empower the development of a new generation of enzymes, molecular tools and therapeutics,” Dr Denes said.

“We made this system open source for the research community, and we are excited to see what people use it for, our goals will be to enhance gene-editing technologies, or to fine tune mRNA medicines for more potent and specific effects,” Professor Neely said.