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Credit: https://www.ucsf.edu/news/2019/07/415031/limitless-potential-artificial-protein-ushers-new-era-smart-cell-therapies

New artificial protein spearheads the era of smart cell therapy

January 21, 2021

In 2019, scientists developed smart cells with the ability to detect the damage caused by a disease or ailment in the body.
These cells function autonomously thanks to an artificial protein known as LOCKR.
Researchers believed that the smart cells could be used to treat a number of diseases that are currently untreatable.

We’re living in an age of discovery where new therapies are being availed every year to treat ailments and diseases. But despite these groundbreaking therapies, the world of medicine still has a recurring problem… Therapies tend to be safe and effective only when they’re being administered at the right time, and in the right doses. However, when given too early or too late, they can be quite ineffective and harmful. The question is, how do doctors know the right period to dispense them? In 2019, a team of bioengineers aimed to change all this. Spearheaded by UC San Francisco’s Hana El Samad, they developed smart cells that behave like tiny autonomous robots. These cells can be used to detect any disease and the damage that it has caused; all while dispensing just the right amount of help at the right time. What’s even more intriguing is that these cells function without any direct human intervention, all thanks to a pioneering artificial protein. The artificial protein in question was designed on a computer and synthesized in a lab. It can be used to manufacture brand-new biological circuits inside living cells. These circuits then transform ordinary cells into smart cells endowed with remarkable abilities. The protein is known as the Latching Orthogonal Cage-Key pRotein or LOCKR. It was first introduced to the world in a series of papers published on July 24th, 2019. And it’s quite unique; unlike anything biologists have ever seen before! In its simple structure, the LOCKR protein resembles a barrel, which when open, reveals a molecular arm that’s been engineered to control virtually any cellular process. In the first of the two papers published by the researchers, scientists described the protein as an arm that can direct molecular traffic inside the cells, thereby degrading specific proteins, and initiating the cell’s self-destruct process. But there’s a flip side to this: LOCKR’s arms will remain hidden until the barrel is opened. As the name of the protein suggests, the barrel remains closed until it comes across a molecular key. The molecular key in question is a protein that is designed to fit seamlessly into the barrel’s lock. In the event that the key is not present, LOCKR, in its essence, is switched off, and the key is subsequently switched on. The ability to control when LOCKR is on and off makes the synthesized protein behave a lot like an electric switch. Despite switches being simple, and perhaps even primitive in their design, they still remain a basic building block in many of the modern electronics we use today. As a matter of fact, in the second of the two papers, scientists were able to discuss the impressive circuit-building capabilities of this protein. Using a version of the tool called degronLOCKR—which can be switched on and off to degrade a protein of interest—the researchers were able to construct circuits that could dynamically regulate cellular activity in response to cues from the cell’s internal and external environment. When the circuits—which include a genetically encoded sensor—detected a disruption of normal cell activity, degron LOCKR responded by destroying the proteins that direct cellular responses. Nevertheless, the use of degronLOCKR to construct new biological circuits can be a breakthrough in the medical fraternity. “LOCKR, and more specifically, degronLOCKR, opens a whole new realm of possibility for programming cells to treat a wide range of debilitating conditions for which safe and effective treatments are not yet available,” says Andrew Ng, PHD and co-first author of the two studies. Ng worked with El-Samad through the UC Berkeley–UCSF Graduate Program in Bioengineering. El-Samad, Ng, and their collaborators are now working towards building a degronLOCKR-based smart cell that could treat a number of ailments and diseases, including traumatic brain injury (TBI); a condition that highlights the sensitive issue of timing. You see, when the brain incurs a traumatic injury, the body responds by activating a vigorous inflammatory response. Though inflammation is an essential part of the body’s healing process, in TBI, inflammation can rise to unnecessary levels that lead to brain damage. Though doctors can administer drugs to help manage the situation, these drugs often cause inflammation to slow down and prevent proper healing from taking place. In fact, with TBI, neither modern medicine nor the body’s own defenses can achieve just the right level of inflammation to maximize healing without resulting in some form of permanent brain damage. This is where degronLOCKR comes in: The researchers believe they’ll soon be able to transform the patient’s own cells into smart cells by installing degronLOCKR-based circuits that are designed to sense inflammation and modulate the activity of the immune system. The hope is that when these modified cells are reintroduced back into the patient’s body, they will keep the inflammation within the recommended narrow therapeutic zone. TBI isn’t the only condition that scientists believe they can solve with this technology. Smart cells could one day be used to treat a number of diseases that are currently untreatable; from cancers to autoimmune diseases for which no therapies are yet available.

References: https://www.ucsf.edu/news/2019/07/415031/limitless-potential-artificial-protein-ushers-new-era-smart-cell-therapies

New artificial protein spearheads the era of smart cell therapy

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