Artificial protein builds autonomous circuits to control any cellular process.

Bio-computers use systems of biologically derived molecules, such as DNA and proteins, to build circuitry inside cells which can perform computational calculations involving storing, retrieving, and processing data. In turn it is hoped these ‘smart cells’ will lead to smart drugs, living computers inside the body which are able to monitor, target and treat the host body and disease autonomously. Now, a study from researchers led by UC San Francisco develops a transformative biotechnology that enables the construction of biological circuits which gives cells unprecedented capabilities. The team state the novel artificial protein can be used to build brand-new biological circuits inside living cells, transforming ordinary cells into smart cells which are endowed with autonomous abilities. The two studies are published in the journal Nature, whose links can be found here and here.

Previous studies show many therapies are safe and effective only when administered at the right time and in very precise doses, when given too early or too late, in too large or too small an amount, medicines can be ineffective or even harmful. Patient adherence can also be a problem with drug efficacy, with monitoring systems also desirable to detect any problems or disease. The current study develops smart cells that behave like tiny autonomous robots which, in the future, may be used to detect damage and disease, and deliver drugs as and when needed.

The current study designs an artificial protein on a computer which, when synthesized, can be used to build brand-new biological circuits inside living cells. Results show that the protein, dubbed the Latching Orthogonal Cage-Key pRotein, or LOCKR resembles a barrel that, when opened, reveals a molecular arm which can be engineered to control virtually any cellular process. Data findings show the arms can direct molecular traffic inside cells, degrade specific proteins, and initiate the cell’s self-destruct process.

The lab also developed a version of the protein called degronLOCKR, which can be switched on and off to degrade a protein of interest, and can consruct circuits to dynamically regulate cellular activity in response to cues from the cell’s internal and external environments. Results show when the circuits, which included a genetically encoded sensor, detects a disruption of normal cell activity, degronLOCKR responds by destroying the proteins causing the disruption to the cellular software, until the cell returns to normal.

The team surmise they have engineered proteins for generating complex synthetic circuitry in cells for biotechnological and therapeutic applications. For the future, the researchers plan to transform cells in vivo into smart cells by installing degronLOCKR-based circuits, to treat a variety of diseases and ailments, including traumatic brain injury.

Source: University of California San Francisco

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