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  • Jags Pandhal

Microalgae as a factory to make therapeutics to target inflammatory bowel disease

Inflammatory bowel disease (IBD) affects millions of people worldwide, posing a substantial social and economic burden to governments and health systems. Worst still, rates are rising. IBD is a chronic immunological disorder affecting the gastrointestinal tract, and despite the risk of serious illness, no curative treatments are available. By immunological, we mean that the disease is associated with a failure in immune regulatory mechanisms, resulting in inflammation, production of pro-inflammatory cytokines. Eventually, tissues are destroyed, and tumours can develop.


One potential treatment is to target the inflammatory cytokines by introducing anti-inflammatory cytokines to the patient. These not only stop inflammation but can also repair damaged tissues. The challenge is to deliver enough of a dose to where the problem is, the gastrointestinal mucosa. Recent attention has shifted to testing oral delivery of anti-transgenic cytokines, such as TGF-β, produced in “friendly” bacteria. TGF-β is widely beneficial in immune suppression and wound repair.


An exciting new strategy to help with IBD has come from an unexpected source, our most common parasite, helminth worms. One species has been shown to secrete a potent TGF-β mimic called TGM1 when patients are deliberately infected. However, rather than infecting patients with helminth worms, could edible green algae that have been engineered to express recombinant TGM1 do the trick?


In this study a team of researchers from UCSD, University of Glasgow and The University of Sheffield expressed TGM1 in the green algae Chlamydomonas reinhardtii and fed it directly to mice to assess the protein’s action from within the gastrointestinal tract. Not only is this alga safe to eat, its incredibly cheaper to grow than other host cell systems, especially mammalian cells such as Chinese Hamster Ovary cells. It’s also complex enough to ensure correct folding of human proteins, unlike many bacteria. Our study showed that algal TGM1 has comparable post-translational modifications to human proteins, and when administered orally to mice, it successfully regulated immune cells, reducing weight loss as well as disease symptoms. Overall the research in this paper provides further evidence of the merits into developing C. reinhardtii into both a protein therapeutic production and delivery system, rolled into one.


Read the full paper here...https://pubmed.ncbi.nlm.nih.gov/34390759/




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