---
_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'
...