PROTEUS is a truly disruptive technology that will change the way proteins are evolved. Most importantly, it has the potential to stimulate the development of much-needed new vaccines and therapeutics. This novel system produces millions of genetic variants over hundreds of thousands to millions of cells. It’s making the protein evolution process much quicker, cutting what once could take months or years down to mere weeks.
PROTEUS is a remarkable advancement in our ability to understand and manipulate proteins. It employs an innovative approach that begins with individually engineering one gene sequence into a virus’s genome. This in turn enables researchers to create millions of genetic variants chosen in parallel, massively speeding up the overall pace of discovery. In May, a novel European study demonstrating the technology was published in the open-access journal Nature Communications. Most importantly, it placed the data and genomic sequences into the public academic space.
Accelerating Protein Evolution
The PROTEUS system enables all three critical steps in a single round of evolution: diversification, selection, and amplification. Each cycle is only 24 hours long, which provides bandwidth for quick iteration and development. Christopher Denes, a researcher on the project, provided this analogy to help understand the process of directed evolution. He described it as a recursive approach—we generate diversity in a target gene, choose the fittest variants according to the imposed challenges, then amplify those successful versions to begin the loop anew.
VLVs can be generated by PROTEUS which are virus-like in morphology, but replicate their genome within 24 hours. This fast-tracked process often creates mutations in the target gene. This mutation process is absolutely critical. It produces a vigorous crowd of potential genetic variants from which we can pick the most promising ones. Denes expanded on this idea by explaining, “In under a day, these VLVs replicate their genome in preparation to replicate. This replication step is error-prone—often creating mutations in the gene we want to evolve.
Long-term, the PROTEUS system is highly affordable. The whole evolution process is less than a few thousand dollars! This economical use of funds is especially advantageous to campaigns aimed at multi-gene targets. Due to this property, it becomes a lucrative model for academia and the pharmaceutical industry.
Applications in Medicine and Research
Beyond just our work, PROTEUS has far-reaching consequences for understanding how proteins—particularly membrane proteins—evolved. Its uses range from formulating opioids to producing medicine to help lose weight and life-threatening viral resistance. Denes touched on the flexibility of PROTEUS. As he put it, “PROTEUS is able to produce mammalian-specific adaptations that we never anticipated or evolved in other systems.”
The technology in a very short time accelerated the development of CRISPR tools. This groundbreaking development is potentially revolutionary for both research and medicine. Denes painted a picture of the promise of evolved CRISPR tools. As he put it, “These are things that would be just amazing tools for research and medicine.” This is an exciting element, because it demonstrates how PROTEUS can serve to connect the dots between theoretical research and real-world application.
Kate Adamala, another researcher interested in PROTEUS, expressed her enthusiasm about its potential applications: “If my lab had PROTEUS, I’d start with membrane proteins because that’s a huge area and incredibly attractive from a human health perspective.”
A New Era of Genetic Research
PROTEUS is big, really big. In a test tube, it’s capable of churning out up to 15 billion virus-like vesicles. This capacity greatly enhances the return on investment of research projects. Yet it opens the door to transformative discoveries that were previously impossible.
Denes likened this to the way viruses including SARS-CoV-2 adapted with several different strains. He detailed how this is the same way that SARS-CoV-2 has adapted and evolved with variants like Alpha to Delta, and now Omicron. He further explained that our genetic challenge imposes selection pressure, culling out all the “bad” variants, but actually enhancing the “good” ones.
The continued testing and future development of PROTEUS represents a step away from crude, blunt force approaches in the field of genetic engineering. With the new Image Based Science tool, researchers will be able to take their powerful ability to solve complicated biological puzzles to an entirely new level.
