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Chemically inducible split protein regulators for mammalian cells

التفاصيل البيبلوغرافية
العنوان: Chemically inducible split protein regulators for mammalian cells
المؤلفون: Erik, Rihtar, Tina, Lebar, Duško, Lainšček, Katarina, Kores, Samo, Lešnik, Urban, Bren, Roman, Jerala
المصدر: Nature Chemical Biology. 19:64-71
بيانات النشر: Springer Science and Business Media LLC, 2022.
سنة النشر: 2022
مصطلحات موضوعية: Mammals, Gene Expression Regulation, Animals, Humans, Synthetic Biology, Cell Biology, Ligands, Protein Engineering, Molecular Biology
الوصف: Chemically inducible systems represent valuable synthetic biology tools that enable the external control of biological processes. However, their translation to therapeutic applications has been limited because of unfavorable ligand characteristics or the immunogenicity of xenogeneic protein domains. To address these issues, we present a strategy for engineering inducible split protein regulators (INSPIRE) in which ligand-binding proteins of human origin are split into two fragments that reassemble in the presence of a cognate physiological ligand or clinically approved drug. We show that the INSPIRE platform can be used for dynamic, orthogonal and multiplex control of gene expression in mammalian cells. Furthermore, we demonstrate the functionality of a glucocorticoid-responsive INSPIRE platform in vivo and apply it for perturbing an endogenous regulatory network. INSPIRE presents a generalizable approach toward designing small-molecule responsive systems that can be implemented for the construction of new sensors, regulatory networks and therapeutic applications.
تدمد: 1552-4469
1552-4450
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4caed33138d9a406057a92315321bb3f
https://doi.org/10.1038/s41589-022-01136-x
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....4caed33138d9a406057a92315321bb3f
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15524469
15524450