Application of a commensal gut bacterium for the controlled delivery of heterologous proteins to the lower GI tract

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We have developed a novel protein delivery technology that uses the human gut commensal bacteria, Bacteroides ovatus (Bo) for the (diet) controlled delivery of biologically active proteins to the gastrointestinal tract. The rationale for developing this technology was based on the need for more targeted and controlled delivery of immunomodulatory agents to the gastrointestinal (GI) tract. The key objectives of this application are to develop further the Bo heterologous protein delivery platform technology using two model GM-strains, Bo-TGF that produces human transforming growth factor-beta1 (TGFb1), and Bo-NoV that produces norovirus virus like particles (VLPs). This will be achieved through:
(a) Platform development; including dosing regimen development and using in vitro models of the human GI-tract.
(b) Risk Reduction; by determining the impact of GM-Bo on human commensal bacteria in an in vitro colon model, and demonstrating persistence, induction of therapeutic delivery and clearance by metronidazole.
(c) Efficacy in vivo; use of additional animal models, and
(d) Strain Functionality.
The final output will be a robustly tested platform technology for the delivery of biologics that is suitable for first in man studies and ready for commercial uptake.

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