A platform of genetically engineered bacteria as vehicles for localized delivery of therapeutics: Toward applications for Crohn's disease.

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TitleA platform of genetically engineered bacteria as vehicles for localized delivery of therapeutics: Toward applications for Crohn's disease.
Publication TypeJournal Article
Year of Publication2018
AuthorsMckay, R, Ghodasra, M, Schardt, J, Quan, D, Pottash, AEli, Shang, W, Jay, SM, Payne, GF, Chang, MWook, March, JC, Bentley, WE
JournalBioeng Transl Med
Volume3
Issue3
Pagination209-221
Date Published2018 Sep
ISSN2380-6761
Abstract

For therapies targeting diseases of the gastrointestinal tract, we and others envision probiotic bacteria that synthesize and excrete biotherapeutics at disease sites. Toward this goal, we have engineered commensal E. coli that selectively synthesize and secrete a model biotherapeutic in the presence of nitric oxide (NO), an intestinal biomarker for Crohn's disease (CD). This is accomplished by co-expressing the pore forming protein TolAIII with the biologic, granulocyte macrophage-colony stimulating factor (GM-CSF). We have additionally engineered these bacteria to accumulate at sites of elevated NO by engineering their motility circuits and controlling pseudotaxis. Importantly, because we have focused on test beds, motility and biotherapeutics production are spatiotemporally characterized. Together, the targeted recognition, synthesis, and biomolecule delivery comprises a "smart" probiotics platform that may have utility in the treatment of CD. Further, this platform could be modified to accommodate other pursuits by swapping the promoter and therapeutic gene to reflect other disease biomarkers and treatments, respectively.

DOI10.1002/btm2.10113
Alternate JournalBioeng Transl Med
PubMed ID30377661
PubMed Central IDPMC6195910