A platform of genetically engineered bacteria as vehicles for localized delivery of therapeutics: Toward applications for Crohn's disease
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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 01, 2018
- Source ID
- 10.1002/btm2.10113
Entities
People
- Alex Eli Pottash
- David Quan
- Gregory F Payne
- John C. March
- John Schardt
- Matthew Wook Chang
- Monil Ghodasra
- Ryan Mckay
- Steven M. Jay
- William E. Bentley
- Wu Shang
Organizations
- American Association of Pharmaceutical Scientists
- Cornell University
- Defense Threat Reduction Agency
- Division of Chemical, Bioengineering, Environmental, and Transport Systems
- Division of Materials Research
- Elsa U. Pardee Foundation
- National Cancer Institute
- National Heart, Lung, and Blood Institute
- National Institute of Biomedical Imaging and Bioengineering
- National Institutes of Health
- University of Maryland