Cells would detect damage or disease, delivering drugs when needed.

Treating many diseases is challenging because drugs often must be delivered at a certain stage of the disease development and at a certain dose. Incorrect timing of doses can be ineffective or even harmful.

Researchers at the University of California San Francisco and the University of Washington may have found the solution with the development of an artificial protein capable of constructing new biological circuitry inside living cells. The new circuits convert regular cells into “smart” cells that can detect and treat damaged cells and tissues.

The Latching Orthogonal Cage-Key pRotein (LOCKR) was initially designed using computation models and then synthesized in the lab. It is not like any natural protein, and, according to the researchers, it allows them a high level of control over how it interacts with other cellular components. It has a barrel-like structure containing a molecule arm that, when released, can be engineered to control most any cellular process, such as directing molecular traffic inside cells, degrading specific proteins and initiating cell self-destruction.

A molecular “key” is required to release the arm, which makes the protein similar to a miniaturized on/off switch; it is a fundamental building block for the construction of new biological circuitry.

In one example, the scientists developed degronLOCKR, a version of the protein that can be switched on and off to degrade a protein of interest. When a disruption of normal cell activity was detected, degronLOCKR responded by destroying the proteins that caused the disruption until cell functioning returned to normal.

Overall, this particular “switch” can potentially be used to construct circuits that could dynamically regulate cellular activity in response to cues from the cell’s internal and external environment and could be applicable to treating diseases for which no current treatment option exists.

The researchers are currently developing degronLOCKR-based smart cells that could treat a variety of diseases, including traumatic brain injury (TBI), which often involves excessive inflammation in the brain in response to a traumatic injury. It is difficult to treat TBI without reducing the inflammation to levels too low to promote healing. The new LOCKR-based approach would theoretically make it possible to get the level just right using degronLOCKR-based circuits designed to sense inflammation and modulate the activity of the immune system.