4.5 Article

Oral delivery of a functional algal-expressed TGF-β mimic halts colitis in a murine DSS model

Journal

JOURNAL OF BIOTECHNOLOGY
Volume 340, Issue -, Pages 1-12

Publisher

ELSEVIER
DOI: 10.1016/j.jbiotec.2021.08.006

Keywords

Algae; Helminth; Treg; TGM; TGF-beta; Colitis

Funding

  1. Flow Core Facility
  2. Wolfson Research Facility, University of Glasgow
  3. Kenneth Rainin Foundation through Synergy and Innovator Grants [2015-964, 2016-3067]
  4. Wellcome Trust [106122, 219530, 104111]
  5. Medical Research Council

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Inflammatory bowel disease (IBD) is a set of immunological disorders that require new treatment methods. TGM1, derived from a parasite, shows potential as a novel anti-inflammatory bio-therapeutic.
Inflammatory bowel disease (IBD) is a set of immunological disorders which can generate chronic pain and fatigue associated with the inflammatory symptoms. The treatment of IBD remains a significant hurdle with current therapies being only partially effective or having significant side effects, suggesting that new therapies that elicit different modes of action and delivery strategies are required. TGM1 is a TGF-beta mimic that was discovered from the intestinal helminth parasite Heligmosomoides polygyrus and is thought to be produced by the parasite to suppress the intestinal inflammation response to help evade host immunity, making it an ideal candidate to be developed as a novel anti-inflammatory bio-therapeutic. Here we utilized the expression system of the edible green algae Chlamydomonas reinhardtii in order to recombinantly produce active TGM1 in a form that could be ingested. C. reinhardtii robustly expressed TGM1, and the resultant recombinant protein is biologically active as measured by regulatory T cell induction. When delivered orally to mice, the algal expressed TGM1 is able to ameliorate weight loss, lymphadenopathy, and disease symptoms in a mouse model of DSS-induced colitis, demonstrating the potential of this biologic as a novel treatment of IBD.

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