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engineered native E. coli strains expressing bile salt hydrolase and interleukin-10

Development stage: Preclinical
Lead developer: University of California, San Diego
Modality: Synthetic Biology Platforms → Engineered Microbial Therapeutics → Microbiome Therapeutics, Fresh FMT → Fecal Microbiota Transplantation (FMT) → Microbiome Therapeutics, Yeast Strains → Single Strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Bacterial Strains → Single Strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Defined Consortia → Multi-strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Frozen FMT → Fecal Microbiota Transplantation (FMT) → Microbiome Therapeutics, Genetically Modified Bacteria → Engineered Microbial Therapeutics → Microbiome Therapeutics, Microbial Metabolites → Microbiome-Derived Products → Microbiome Therapeutics, Microbial Proteins → Microbiome-Derived Products → Microbiome Therapeutics, Complex Communities → Multi-strain Products → Live Biotherapeutic Products → Microbiome Therapeutics
Administration: Oral

Overview

Engineered native E. coli strains expressing bile salt hydrolase (BSH) and interleukin-10 (IL-10) are live bacterial therapeutics designed to provide persistent beneficial functions in the host gut microbiome. These engineered bacteria are created by isolating native E. coli from a host, modifying them to express specific transgenes (BSH and IL-10), and then reintroducing them to the host. BSH is a prokaryotic bile acid deconjugation enzyme that can affect host metabolic homeostasis, while IL-10 is a mammalian cytokine that functions as an anti-inflammatory agent. After a single treatment, these engineered bacteria can engraft throughout the entire gut, retain transgene functionality, induce metabolomic changes, affect host physiology, and potentially ameliorate pathophysiological conditions. BSH activity has been associated with improved insulin sensitivity in mouse models of Type 2 diabetes.

Targets

IL10RA (Interleukin-10 Receptor)

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