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trp 5xGLP-1
- Development stage
- Preclinical
- Lead developer
- Karolinska Institutet
- Modality
- Defined Consortia → Multi-strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Microbial Metabolites → Microbiome-Derived Products → Microbiome Therapeutics, Synthetic Biology Platforms → Engineered Microbial Therapeutics → Microbiome Therapeutics, Fresh FMT → Fecal Microbiota Transplantation (FMT) → Microbiome Therapeutics, Genetically Modified Bacteria → Engineered Microbial Therapeutics → Microbiome Therapeutics, Peptides, Recombinant Proteins and Enzymes, Bacterial Strains → Single Strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Yeast Strains → Single Strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Frozen FMT → Fecal Microbiota Transplantation (FMT) → Microbiome Therapeutics, Microbial Proteins → Microbiome-Derived Products → Microbiome Therapeutics, Complex Communities → Multi-strain Products → Live Biotherapeutic Products → Microbiome Therapeutics
- Administration
- Oral
01
Overview
trp 5xGLP-1 is an experimental, trypsin-stabilized pentameric analogue of glucagon-like peptide-1 (GLP-1) developed for the oral treatment of type 2 diabetes. The molecule consists of five GLP-1 monomers (specifically the GLP-1-Gly8 variant, which is resistant to dipeptidyl peptidase-4) linked by sequences containing intestinal trypsin cleavage sites. This design allows the pentamer to function as a prodrug that is enzymatically cleaved into active monomeric GLP-1 upon reaching the small intestine. The construct has been evaluated as a cargo for delivery by recombinant *Lactobacillus paracasei* (in both secreted and surface-anchored forms) and as a purified peptide. In preclinical models using diabetic Goto-Kakizaki (GK) rats, trp 5xGLP-1 demonstrated insulinotropic activity and improved glycemic control when delivered directly to the intestine via intubation, though oral delivery via live biotherapeutic vehicles showed limited efficacy due to low expression levels.
- Other names
- trypsin-stabilized pentameric GLP-15×GLP-1pentameric GLP-1
02
Targets
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