Smyth, D. J. et al. (2021) Oral delivery of a functional algal-expressed TGF-β mimic halts colitis in a murine DSS model. Journal of Biotechnology, 340, pp. 1-12. (doi: 10.1016/j.jbiotec.2021.08.006) (PMID:34390759) (PMCID:PMC8516079)
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Abstract
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-β 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.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the Kenneth Rainin Foundation through Synergy and Innovator Grants (Refs 2015-964 and 2016-3067), the U.S. Department of Energy (DE-EE0008246), the Wellcome Trust through Investigator Awards to RMM (Ref 106122 and 219530), the Wellcome Trust core-funded Wellcome Centre for Integrative Parasitology (Ref: 104111), and by the Medical Research Council Confidence-in-Concept scheme. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | McManus, Miss Caitlin and Shek, Ms Vivien and Maizels, Professor Rick and Webster, Miss Holly |
| Creator Roles: | McManus, C.Writing – review and editing Webster, H.Writing – review and editing Shek, V.Writing – review and editing Maizels, R. M.Conceptualization, Supervision, Funding acquisition, Writing – review and editing |
| Authors: | Smyth, D. J., Ren, B., White, M., McManus, C., Webster, H., Shek, V., Evans, C., Pandhal, J., Fields, F., Maizels, R. M., and Mayfield, S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | Journal of Biotechnology |
| Publisher: | Elsevier |
| ISSN: | 0168-1656 |
| ISSN (Online): | 1873-4863 |
| Published Online: | 12 August 2021 |
| Copyright Holders: | Copyright © 2021 The Authors |
| First Published: | First published in Journal of Biotechnology 340: 1-12 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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