--- _id: '7360' abstract: - lang: eng text: Inflammation, which is a highly regulated host response against danger signals, may be harmful if it is excessive and deregulated. Ideally, anti-inflammatory therapy should autonomously commence as soon as possible after the onset of inflammation, should be controllable by a physician, and should not systemically block beneficial immune response in the long term. We describe a genetically encoded anti-inflammatory mammalian cell device based on a modular engineered genetic circuit comprising a sensor, an amplifier, a “thresholder” to restrict activation of a positive-feedback loop, a combination of advanced clinically used biopharmaceutical proteins, and orthogonal regulatory elements that linked modules into the functional device. This genetic circuit was autonomously activated by inflammatory signals, including endogenous cecal ligation and puncture (CLP)-induced inflammation in mice and serum from a systemic juvenile idiopathic arthritis (sIJA) patient, and could be reset externally by a chemical signal. The microencapsulated anti-inflammatory device significantly reduced the pathology in dextran sodium sulfate (DSS)-induced acute murine colitis, demonstrating a synthetic immunological approach for autonomous anti-inflammatory therapy. article_processing_charge: No article_type: original author: - first_name: Anže full_name: Smole, Anže last_name: Smole - first_name: Duško full_name: Lainšček, Duško last_name: Lainšček - first_name: Urban full_name: Bezeljak, Urban id: 2A58201A-F248-11E8-B48F-1D18A9856A87 last_name: Bezeljak orcid: 0000-0003-1365-5631 - first_name: Simon full_name: Horvat, Simon last_name: Horvat - first_name: Roman full_name: Jerala, Roman last_name: Jerala citation: ama: Smole A, Lainšček D, Bezeljak U, Horvat S, Jerala R. A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation. Molecular Therapy. 2017;25(1):102-119. doi:10.1016/j.ymthe.2016.10.005 apa: Smole, A., Lainšček, D., Bezeljak, U., Horvat, S., & Jerala, R. (2017). A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation. Molecular Therapy. Elsevier. https://doi.org/10.1016/j.ymthe.2016.10.005 chicago: Smole, Anže, Duško Lainšček, Urban Bezeljak, Simon Horvat, and Roman Jerala. “A Synthetic Mammalian Therapeutic Gene Circuit for Sensing and Suppressing Inflammation.” Molecular Therapy. Elsevier, 2017. https://doi.org/10.1016/j.ymthe.2016.10.005. ieee: A. Smole, D. Lainšček, U. Bezeljak, S. Horvat, and R. Jerala, “A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation,” Molecular Therapy, vol. 25, no. 1. Elsevier, pp. 102–119, 2017. ista: Smole A, Lainšček D, Bezeljak U, Horvat S, Jerala R. 2017. A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation. Molecular Therapy. 25(1), 102–119. mla: Smole, Anže, et al. “A Synthetic Mammalian Therapeutic Gene Circuit for Sensing and Suppressing Inflammation.” Molecular Therapy, vol. 25, no. 1, Elsevier, 2017, pp. 102–19, doi:10.1016/j.ymthe.2016.10.005. short: A. Smole, D. Lainšček, U. Bezeljak, S. Horvat, R. Jerala, Molecular Therapy 25 (2017) 102–119. date_created: 2020-01-25T15:55:39Z date_published: 2017-01-01T00:00:00Z date_updated: 2021-01-12T08:13:14Z day: '01' ddc: - '570' department: - _id: MaLo doi: 10.1016/j.ymthe.2016.10.005 external_id: pmid: - '28129106' file: - access_level: open_access checksum: ea8b1b28606dd1edab7379ba4fa3641f content_type: application/pdf creator: dernst date_created: 2020-03-03T10:55:13Z date_updated: 2020-07-14T12:47:56Z file_id: '7561' file_name: 2017_MolecularTherapy_Smole.pdf file_size: 3404806 relation: main_file file_date_updated: 2020-07-14T12:47:56Z has_accepted_license: '1' intvolume: ' 25' issue: '1' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '01' oa: 1 oa_version: Published Version page: 102-119 pmid: 1 publication: Molecular Therapy publication_identifier: issn: - 1525-0016 publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 25 year: '2017' ...