Artificial protein programs cells to fight disease

Cells
University of California, San Francisco and University of Washington researchers created a protein that can be switched on and off to degrade disease-causing proteins in cells. (Pixabay/qimono)

What if cells could sense the onset of disease and then modulate the immune system to administer just the right amount of healing power to clear the illness without affecting normal tissues? Scientists at the University of California, San Francisco (UCSF) and the University of Washington have designed an artificial protein that they believe will make such “smart” therapies a reality.

A team of bioengineers described the invention, called Latching Orthogonal Cage-Key pRotein (LOCKR), in two new papers published in the journal Nature. LOCKR was built with a molecular “arm” that can be directed to control cellular processes by unlocking it with another engineered protein, according to a statement from UCSF.

So how exactly would LOCKR work in the treatment of disease? The researchers use traumatic brain injury (TBI) as an example. When TBI occurs, physicians respond by administering medicines to tamp down the massive brain inflammation that occurs when the body attempts to repair the damage. But sometimes these drugs work too well, and inflammation drops so low the brain can’t heal properly.

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Installing LOCKR in the patient’s cells could help keep inflammation levels in check, leaving just enough to promote healing, the UCSF team said. They believe a similar concept could be used to treat a variety of diseases, from cancer to autoimmune disorders.

Because LOCKR is entirely human-made, it “provides an unprecedented level of control over the way the protein interacts with other components of the cell,” said Hana El-Samad, Ph.D., professor of biochemistry and biophysics at UCSF and co-senior author of the research, in the statement. That, she added, “will allow us to begin tackling unsolved—and previously unsolvable—problems in biology, with important implications for medicine and industry.” LOCKR was co-invented by University of Washington biochemistry professor David Baker, Ph.D.

RELATED: BIO: Meet Refuge Biotech, the company developing 'intelligent' cell therapies

The UCSF and University of Washington bioengineers developed a version of their new tool, dubbed degronLOCKR, which can be turned on to degrade specific proteins in cells. It includes “circuits” that regulate cellular activity in response to cues from the environment, they reported. When the circuits detected a disruption inside the cell, degronLOCKR destroyed proteins that caused the problem, then turned off once the cell returned to normal.

Reprogramming cells to fight disease is a concept that’s already been borne out, in CAR-T cell therapies for cancer, for example. But several research groups and companies are searching for the next generation of products that can, in essence, direct the body’s cells to fight off diseases.

Among them is Refuge Biotech, which recently described to FierceBiotech its process for using CRISPR gene editing to create “intelligent” T-cell therapies that the company’s scientists hope will be able to fight solid tumors.

And several tech giants, including Apple and IBM, are looking to combine their latest inventions with biology to fight a range of diseases. Earlier this year, Microsoft partnered with Princeton University, Oxford Biomedica and Synthace to improve gene-therapy technology using machine learning.

El-Samad, Baker and colleagues liken LOCKR to an electric switch for cells—one that they can use to build tiny but complex integrated circuits to control healing. They plan to build new versions of the system, similar to degronLOCKR, to create “precise and robust live cell therapies,” El-Samad said.

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