Open AccessA platform of genetically engineered bacteria as vehicles for localized delivery of therapeutics: Toward applications for Crohn's disease
Author(s) -
McKay Ryan,
Ghodasra Monil,
Schardt John,
Quan David,
Pottash Alex Eli,
Shang Wu,
Jay Steven M.,
Payne Gregory F.,
Chang Matthew Wook,
March John C.,
Bentley William E.
Publication year - 2018
Publication title -
bioengineering and translational medicine
Language(s) - English
Resource type - Journals
ISSN - 2380-6761
DOI - 10.1002/btm2.10113
Subject(s) - synthetic biology , secretion , disease , genetically engineered , motility , gastrointestinal tract , crohn's disease , bacteria , biology , immunology , medicine , computational biology , microbiology and biotechnology , gene , biochemistry , genetics , pathology
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 in vitro 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.