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

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)

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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, Caitlin and Maizels, Professor Rick and Webster, Miss Holly and Shek, Ms Vivien
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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302175Induction of Therapeutic Regulatory T cells by Parasite ProductsRichard MaizelsThe Kenneth Rainin Foundation (KENRAIN)2016-3067III - Parasitology
173801Helminths and the Immune System: Regulation, Regulators and ImmunityRichard MaizelsWellcome Trust (WELLCOTR)106122/A/14/ZInstitute of Infection, Immunity & Inflammation
308411Molecular and Cellular Interactions in Helminth InfectionsRichard MaizelsWellcome Trust (WELLCOTR)219530/Z/19/ZIII - Parasitology
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZRIII - Parasitology