Biological Artificial Intelligence: The PROTEUS System Reshaping Molecular Design And Gene Therapies

Australian researchers have crafted a novel research system that employs 'biological artificial intelligence' to design and evolve molecules with enhanced or new functions directly within mammalian cells. This innovative system, named PROTEUS, offers a potent tool for scientists aiming to develop more precise research tools or gene therapies.

The PROTEUS system leverages 'directed evolution', a laboratory technique that mimics natural evolutionary processes. Unlike traditional methods that take years, this approach accelerates evolution cycles, enabling the creation of molecules with new functions in mere weeks. This advancement could significantly impact the discovery of new medicines.

Enhancing Gene Editing Technology

PROTEUS can be applied to improve gene editing technologies like CRISPR, enhancing their effectiveness. "This means PROTEUS can be used to generate new molecules that are highly tuned to function in our bodies," explains Professor Greg Neely from the University of Sydney. "We can use it to make new medicine that would be otherwise difficult or impossible to make with current technologies."

Unlike previous methods primarily working in bacterial cells, PROTEUS evolves molecules within mammalian cells. It can tackle complex problems by exploring millions of potential sequences not yet existing naturally, finding solutions that might take human researchers years to discover.

Applications and Potential

The researchers have already used PROTEUS to develop improved protein versions easily regulated by drugs and nanobodies capable of detecting DNA damage, a crucial process driving cancer. However, its applications extend beyond these examples, potentially enhancing most proteins and molecules.

This research was conducted at the Charles Perkins Centre at the University of Sydney in collaboration with the Centenary Institute. The findings were published in Nature Communications.

Overcoming Challenges

The original development of directed evolution in bacteria was honoured with the 2018 Nobel Prize in Chemistry. "The invention of directed evolution changed the trajectory of biochemistry," says Dr. Christopher Denes from the Charles Perkins Centre. "Now, with PROTEUS, we can program a mammalian cell with a genetic problem we aren't sure how to solve."

A significant challenge faced by Dr. Denes and his team was ensuring mammalian cells could endure multiple evolution cycles without cheating by finding trivial solutions. They overcame this by using chimeric virus-like particles combining genes from different viruses.

Future Prospects

This design allowed cells to process various solutions simultaneously, with successful ones becoming dominant while incorrect ones vanished. "PROTEUS is stable, robust and has been validated by independent labs," Dr. Denes states. "We welcome other labs to adopt this technique."

"We made this system open source for the research community," adds Professor Neely. "Our goals will be to enhance gene-editing technologies or fine-tune mRNA medicines for more potent and specific effects." The potential applications are vast, empowering the development of new enzymes, molecular tools, and therapeutics.