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Team:Imperial College London/Project Overview
From 2009.igem.org
Project Overview
The inspiration behind The E.ncapsulator was the inherent difficulty in delivering protein pharmaceuticals to the gut. Due to the delicate nature of proteins and the highly acidic environment present in the stomach, protein molecules are readily broken down - making oral drug delivery of protein pharmaceuticals impossible. The E.ncapsulator is a novel protein manufacture and delivery platform designed to overcome these difficulties.
Modularity is key to the design of The E.ncapsulator. In order to simplify the system, and to increase reusability, the system has been divided into 3 active modules. These are as follows:
- Module 1: Protein Production
- The first module involves engineering E.coli to synthesise the protein drug of interest to sufficient quantities.
- The first module involves engineering E.coli to synthesise the protein drug of interest to sufficient quantities.
- Module 2: Encapsulation
- E.coli coats itself in a protective layer of colanic acid to form the E.ncapsulator. This protective capsule is what protects the biopharmaceutical against the harsh acidic environment of the stomach. This module also codes for the production of a protective sugar, trehalose, which will protect the protein of interest under storage conditions, and will allow for freeze drying.
- E.coli coats itself in a protective layer of colanic acid to form the E.ncapsulator. This protective capsule is what protects the biopharmaceutical against the harsh acidic environment of the stomach. This module also codes for the production of a protective sugar, trehalose, which will protect the protein of interest under storage conditions, and will allow for freeze drying.
- Module 3: Genome Deletion
- The third module, genome deletion, is composed of a ‘suicide trigger’ mechanism that destroys the genetic material of the bacteria, leaving the cell membrane left intact. This killing strategy means the biopharmaceutical remains protected even after the cell is dead.
- The third module, genome deletion, is composed of a ‘suicide trigger’ mechanism that destroys the genetic material of the bacteria, leaving the cell membrane left intact. This killing strategy means the biopharmaceutical remains protected even after the cell is dead.
- Release
- Once in the small intestine, the capsule will be naturally degraded by enzymes present, thereby releasing the designed biopharmaceutical to the gut micro biota where it can carry out its intended function.
In order to demonstrate the feasability of The E.ncapsulator as a new drug delivery platform, we have chosen to program the system to manufacture 2 enzyme pharmaceuticals, cellulase and PAH.
