Intein Mediated Ligation of Therapeutic Proteins

Lead Research Organisation: Imperial College London
Department Name: Chemical Engineering

Abstract

The project aligns to the biopharmaceutical industry, which is considered part of industrial biotechnology. It addresses the challenge of 'difficult-to-express' recombinant proteins. These are complex proteins that induce cellular stress during production, which limits overall yield and increases the costs of production. Our hypothesis is that the proposed strategy of expressing the protein in smaller, easier to express pieces i.e modules and then 'gluing' them together afterwards will increase yield and decrease costs of production. Our strategy is to adopt a modular approach to design and production of biomolecules that will allow modules to be developed independently and shared between multiple final products. Modules will also be expressed in micro-organisms allowing production to move away from the high cost current mammalian cell based process. In future, the same strategy could be used to screen new protein-drugs in high throughput, thereby increasing the productivity of the drug development pipeline.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011178/1 01/10/2015 25/02/2025
1960884 Studentship BB/M011178/1 30/09/2017 31/12/2021 Oskar Lange
BB/R505754/1 01/10/2017 31/12/2021
1960884 Studentship BB/R505754/1 30/09/2017 31/12/2021 Oskar Lange
 
Description We have determined the feasibility of the project by making important therapeutic proteins separately in parts and assembling them together to generate the fully assembled molecules. We have also identified important considerations for the above and are in process of generating data that can be used in optimisation. This has the potential to make therapeutic proteins cheaper to manufacture and allow for the production of variants with enhanced therapeutic efficacy.
Exploitation Route As a proof of concept, this research has opened up many routes for further research surrounding various aspects of the project. These range from optimisation studies to techno-economic analysis and studies testing the therapeutic efficacy of products generated in this way.
Sectors Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology