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INSPIRE - INcucible Split Protein REgulator

Rihtar et al., Nature Chem. Biol., 2022 

Chemical control of the functioning of human cells plays an important role in the design of new gene and cell therapies, as it enables the regulation of the functioning of therapeutic cells via the body's own or imported small molecules. Such a system enables control by the doctor and interruption of any excessive response or autonomous response of the therapeutic cells to the condition in the body. To regulate the action of cellular drugs, researchers have so far mainly used bacterial or plant proteins, which can trigger an unwanted immune response.

Using tools of synthetic biology, we have prepared a new technology for the chemical control of cellular processes, which is based on a person's own proteins, which are capable of binding small molecules, especially clinically tested or the body's own molecules, such as e.g. hormones. The technology, which we named INSPIRE, represents an important new tool in the field of biotechnology and biomedicine, especially for the control of cell and gene therapies, which we successfully demonstrated by detecting an increase in the concentration of the hormone cortisol and a decrease in its action through a feedback loop. We published the results in the prestigious journal  Nature Chemical Biology.

RIHTAR, Erik, LEBAR, Tina, LAINŠČEK, Duško, KORES, Katarina, LEŠNIK, Samo, BREN, Urban, JERALA, Roman. Chemically inducible split protein regulators for mammalian cells. Nature chemical biology. 2023, 19, 64-71, ISSN 1552-4450.


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