Engineering synthetic signalling pathways with programmable dCas9-based chimeric receptors
Synthetic receptors provide a powerful experimental tool for generation of designer cells capable of monitoring the environment, sensing specific input signals, and executing diverse custom response programs. To advance the promise of cellular engineering, we have developed a class of chimeric recep...
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| Format: | Journal article |
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Cell Press
2017
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| _version_ | 1826285171888881664 |
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| author | Baeumler, T Ahmed, A Fulga, T |
| author_facet | Baeumler, T Ahmed, A Fulga, T |
| author_sort | Baeumler, T |
| collection | OXFORD |
| description | Synthetic receptors provide a powerful experimental tool for generation of designer cells capable of monitoring the environment, sensing specific input signals, and executing diverse custom response programs. To advance the promise of cellular engineering, we have developed a class of chimeric receptors that integrate a highly programmable and portable nuclease-deficient CRISPR/Cas9 (dCas9) signal transduction module. We demonstrate that the core dCas9 synthetic receptor (dCas9-synR) architecture can be readily adapted to various classes of native ectodomain scaffolds, linking their natural inputs with orthogonal output functions. Importantly, these receptors achieved stringent OFF/ON state transition characteristics, showed agonist-mediated dose-dependent activation, and could be programmed to couple specific disease markers with diverse, therapeutically relevant multi-gene expression circuits. The modular dCas9-synR platform developed here provides a generalizable blueprint for designing next generations of synthetic receptors, which will enable the implementation of highly complex combinatorial functions in cellular engineering. |
| first_indexed | 2024-03-07T01:24:51Z |
| format | Journal article |
| id | oxford-uuid:919daa0d-0993-4023-ae1a-5bc458058df4 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:24:51Z |
| publishDate | 2017 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:919daa0d-0993-4023-ae1a-5bc458058df42022-03-26T23:19:58ZEngineering synthetic signalling pathways with programmable dCas9-based chimeric receptorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:919daa0d-0993-4023-ae1a-5bc458058df4Symplectic Elements at OxfordCell Press2017Baeumler, TAhmed, AFulga, TSynthetic receptors provide a powerful experimental tool for generation of designer cells capable of monitoring the environment, sensing specific input signals, and executing diverse custom response programs. To advance the promise of cellular engineering, we have developed a class of chimeric receptors that integrate a highly programmable and portable nuclease-deficient CRISPR/Cas9 (dCas9) signal transduction module. We demonstrate that the core dCas9 synthetic receptor (dCas9-synR) architecture can be readily adapted to various classes of native ectodomain scaffolds, linking their natural inputs with orthogonal output functions. Importantly, these receptors achieved stringent OFF/ON state transition characteristics, showed agonist-mediated dose-dependent activation, and could be programmed to couple specific disease markers with diverse, therapeutically relevant multi-gene expression circuits. The modular dCas9-synR platform developed here provides a generalizable blueprint for designing next generations of synthetic receptors, which will enable the implementation of highly complex combinatorial functions in cellular engineering. |
| spellingShingle | Baeumler, T Ahmed, A Fulga, T Engineering synthetic signalling pathways with programmable dCas9-based chimeric receptors |
| title | Engineering synthetic signalling pathways with programmable dCas9-based chimeric receptors |
| title_full | Engineering synthetic signalling pathways with programmable dCas9-based chimeric receptors |
| title_fullStr | Engineering synthetic signalling pathways with programmable dCas9-based chimeric receptors |
| title_full_unstemmed | Engineering synthetic signalling pathways with programmable dCas9-based chimeric receptors |
| title_short | Engineering synthetic signalling pathways with programmable dCas9-based chimeric receptors |
| title_sort | engineering synthetic signalling pathways with programmable dcas9 based chimeric receptors |
| work_keys_str_mv | AT baeumlert engineeringsyntheticsignallingpathwayswithprogrammabledcas9basedchimericreceptors AT ahmeda engineeringsyntheticsignallingpathwayswithprogrammabledcas9basedchimericreceptors AT fulgat engineeringsyntheticsignallingpathwayswithprogrammabledcas9basedchimericreceptors |