Creating ‘The E.ncapsulator’: in situ manufacture and oral delivery of human biopharmaceuticals

This year the Imperial College iGEM team project involves developing an innovative, self-contained drug fabrication and delivery system. We have focused on designing and engineering a number of modules for implementation in Escherichia coli to allow the manufacture of important biopharmaceuticals and the creation of E.ncapsulator tablets for oral delivery and release of protein-based drugs to the small intestine.

The E.ncapsulator provides an elegant solution to a range of human ailments and conditions which cannot currently be successfully treated by oral drugs. Our innovative approach incorporates a number of re-usable modular features including protein drug production, self-encapsulation and genomic neutralisation. Utilising the E.coli bacterium, we are creating a re-usable chassis that will allow the development of a range of biopharmaceuticals to be delivered to the gut.

The first module involves engineering E.coli to synthesise the protein drug of interest to a tuneable threshold. Once accomplished, activation of module two initiates the encapsulation phase, in which E.coli coats itself in a protective layer of colanic acid to form The E.ncapsulator. This protective capsule shields the biopharmaceutical against the harsh acidic environment of the stomach. The third module, genomic neutralisation, is composed of a ‘suicide trigger’ mechanism that destroys the genetic material of the bacteria. Finally, once in the small intestine, the capsule will be degraded releasing the designed biopharmaceutical to the gut micro biota where it can carry out its intended function.

The self-encapsulation of a synthetic biology chassis is new to iGEM and represents a completely novel and innovative approach to biopharmaceutical design, manufacture and delivery. Throughout the project we have followed an engineering approach that incorporates modular design, detailed modelling and simulation and systematic integration. Using such an approach will hopefully lead to The E.ncapsulator coming soon to a Pharmacy near you!