---
_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. <i>Molecular
    Therapy</i>. 2017;25(1):102-119. doi:<a href="https://doi.org/10.1016/j.ymthe.2016.10.005">10.1016/j.ymthe.2016.10.005</a>
  apa: Smole, A., Lainšček, D., Bezeljak, U., Horvat, S., &#38; Jerala, R. (2017).
    A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation.
    <i>Molecular Therapy</i>. Elsevier. <a href="https://doi.org/10.1016/j.ymthe.2016.10.005">https://doi.org/10.1016/j.ymthe.2016.10.005</a>
  chicago: Smole, Anže, Duško Lainšček, Urban Bezeljak, Simon Horvat, and Roman Jerala.
    “A Synthetic Mammalian Therapeutic Gene Circuit for Sensing and Suppressing Inflammation.”
    <i>Molecular Therapy</i>. Elsevier, 2017. <a href="https://doi.org/10.1016/j.ymthe.2016.10.005">https://doi.org/10.1016/j.ymthe.2016.10.005</a>.
  ieee: A. Smole, D. Lainšček, U. Bezeljak, S. Horvat, and R. Jerala, “A synthetic
    mammalian therapeutic gene circuit for sensing and suppressing inflammation,”
    <i>Molecular Therapy</i>, 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.” <i>Molecular Therapy</i>, vol. 25, no. 1, Elsevier,
    2017, pp. 102–19, doi:<a href="https://doi.org/10.1016/j.ymthe.2016.10.005">10.1016/j.ymthe.2016.10.005</a>.
  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
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'
...