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INSRTR: new technological platform for the regulation of protein function

Plaper et al., 2024, Cell Discovery.

Proteins play a key role in all processes in all living organisms; in cellular metabolism, cellular structure formation, recognition, immune response and regulation of other cellular processes. The ability to regulate protein function holds the key to regulating life. Many biological drugs are proteins. We report on a new approach for the regulation of function of diverse proteins, which we named INSRTR, where the function of the protein can be regulated via a short inserted peptide, similar to transistors in electronic circuits. We can either turn the function of a selected protein ON or OFF, and combine them to perform logical operations in living cells.

We demonstrated the new technology in human cells on several enzymes, proteins in cell signaling, DNA recognition and antibodies, used to direct cancer immunotherapy. We prepared a web server that, based on machine learning methods, enables researchers to select the best insertion sites in target proteins. We believe that the INSRTR technology, for which we have filed a patent application, will be very useful both for therapy and for other biotechnological applications.

PLAPER, Tjaša, MERLJAK, Estera, FINK, Tina, SATLER Tadej, LJUBETIČ, Ajasja, LAINŠČEK, Duško, JAZBEC, Vid, BENČINA, Mojca, STEVANOSKA, Sintija, DŽEROSKI, Sašo, JERALA, Roman. Designed allosteric protein logic. Cell Discovery 10, 8 (2024). ISSN 2056-5968, DOI: 10.1038/s41421-023-00635-y

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