Programmable DARPin-based receptors for the detection of thrombotic markers
| العنوان: | Programmable DARPin-based receptors for the detection of thrombotic markers |
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| المؤلفون: | Tobias Strittmatter, Yidan Wang, Adrian Bertschi, Leo Scheller, Patrick C. Freitag, Preetam Guha Ray, Pascal Stuecheli, Jonas V. Schaefer, Thomas Reinberg, Dimitrios Tsakiris, Andreas Plückthun, Haifeng Ye, Martin Fussenegger |
| المساهمون: | University of Zurich, Fussenegger, Martin |
| المصدر: | Nature Chemical Biology, 18 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | therapy, crystal-structure, selection, 610 Medicine & health, Cell Biology, proteins, Ankyrin Repeat, 1307 Cell Biology, Fibrin Fibrinogen Degradation Products, 10019 Department of Biochemistry, 1312 Molecular Biology, 570 Life sciences, biology, Humans, Designed Ankyrin Repeat Proteins, degradation-products, fibrin, Carrier Proteins, Molecular Biology, binders, Protein Binding, Single-Chain Antibodies |
| الوصف: | Cellular therapies remain constrained by the limited availability of sensors for disease markers. Here we present an integrated target-to-receptor pipeline for constructing a customizable advanced modular bispecific extracellular receptor (AMBER) that combines our generalized extracellular molecule sensor (GEMS) system with a high-throughput platform for generating designed ankyrin repeat proteins (DARPins). For proof of concept, we chose human fibrin degradation products (FDPs) as markers with high clinical relevance and screened a DARPin library for FDP binders. We built AMBERs equipped with 19 different DARPins selected from 160 hits, and found 4 of them to be functional as heterodimers with a known single-chain variable fragments binder. Tandem receptors consisting of combinations of the validated DARPins are also functional. We demonstrate applications of these AMBER receptors in vitro and in vivo by constructing designer cell lines that detect pathological concentrations of FDPs and respond with the production of a reporter and a therapeutic anti-thrombotic protein. Nature Chemical Biology, 18 ISSN:1552-4450 ISSN:1552-4469 |
| وصف الملف: | 41589_2022_Article_1095.pdf - application/pdf; application/application/pdf |
| تدمد: | 1552-4469 1552-4450 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::51fce8a517d274f2dac6dbd71e28fa9a https://pubmed.ncbi.nlm.nih.gov/35941237 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....51fce8a517d274f2dac6dbd71e28fa9a |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15524469 15524450 |
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