Cell free expression

Developing a cell free expression system

A novel approach for the production of recombinant proteins

An IUK funded collaborative project brought CPI, Ipsen Biopharm and Touchlight Genetics together to examine the application of cell free expression (CFE) to produce a highly potent product from doggybone DNA (dbDNA™), a novel linear DNA vector.

Cell free expression (CFE) has the potential to revolutionise the supply chain for specific protein products. As stratified and personalised medicines become a reality, the necessity for small batch sizes makes traditional manufacturing approaches prohibitively expensive; the use of CFE offers a cost-effective solution to this manufacturing challenge. 

This project focused on exploring the potential to exploit CFE to manufacture commercial products. The technique has been used as a research tool for many years but had limited interest as a commercial manufacturing platform. A fully scalable CFE platform was therefore developed to facilitate rapid and flexible manufacture of the next generation of biologics.

“ As well as developing a new manufacturing route for Ipsen’s biopharmaceuticals, the Ipsen team have benefitted significantly though the collaborative nature of this research project. Technical discussions and site visits have introduced new equipment and broadened the experience of the scientists working on this project. ”
David Gruber
David Gruber, Head of BioProcess Development – Ipsen 


Touchlight Genetics
Innovate UK



An input is a unique capability, service or method of support that was provided, such as equipment or expertise.

  • Access to CPI’s state of the art bioprocessing facilities 
  • Shared expert technical and industry knowledge 
  • Project scoping, consortia building and proposal development 
  • Current dbDNA™ production process 
  • Provision of a test candidate for assessment of CFE 


An output is the result of the work, such as an experimental finding, an actual product or a pilot demonstrator.

  • Generation of a robust and scalable lysate manufacturing process 
  • Establishment of high throughput screening tools for the rapid assessment of optimal reaction conditions 
  • Development of an optimised and scalable protocol for CFE 
  • Expertise and understanding of the challenges associated with cell free scale-up 
  • Technical knowledge in CFE systems and their optimisation in gene expression 
  • Improved closed loop dbDNA™ vector production process 


An outcome arises from implementing the outputs, for example, a profit, an investment, providing jobs or delivering societal benefits. Outcomes continue once an innovation has been implemented and deliver benefit every year.

  • A new manufacturing route for biopharmaceuticals 
  • Benefits to the supply chain as biopharmaceuticals and vaccines can be manufactured faster with increased flexibility 
  • Benefits to patients as the supply of biological medicines can be improved 

The challenge

Current processes rely on protein expression in cells either endogenously encoded or genetically modified and manufacturing processes for biopharmaceutical products such as therapeutic neurotoxins present significant manufacturing challenges. A CFE platform has the potential to be both scalable and flexible towards the application of niche products and could prove a very powerful tool for industry. CPI, Ipsen and Touchlight worked together to address these challenges with the aim of assessing the viability of using CFE for commercial manufacture of the test candidate product.

How CPI helped

CPI utilised their state-of-the-art facilities and expertise to support the development of a CFE platform which can be applied across a range of products and scales. The scope included generating a simplified scalable production method, from laboratory to pilot scale suitable for the manufacture of a range of recombinant proteins. CPI utilised its high throughput screening tools combining liquid handling platforms and statistical experimental design for optimising reaction conditions for CFE which resulted in scale-up and transfer of a robust CFE system for production of a highly potent product.

Through this collaborative project, a new manufacturing route for biopharmaceuticals was developed which significantly benefits the supply chain as biopharmaceuticals and vaccines can be manufactured faster with increased flexibility. 




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