How to rescue a protein project
Even the most promising recombinant protein projects can end up mothballed, delayed or cancelled because of unexpected technical difficulties – often at considerable cost.
Precious time, effort and skill are spent matching a commercial opportunity with a promising protein or peptide. All too often, though, the difficulty of manufacturing a viable product at a commercial scale causes projects to stall.
‘The product is the process’ is a popular industry saying that acquires new meaning once the technical pitfalls of manufacturing recombinant proteins have been experienced. Without the right process, you don’t have a viable product.
Missing skill sets
Manufacturing expertise is a key skill set that many businesses developing protein and peptide products are inclined to overlook. However, this knowledge gap becomes obvious when the familiar challenges of recombinant protein manufacture rear their ugly heads.
Insufficient titre is one. Complex downstream processing that leads to high losses of expensive protein is another. Common issues include reducing or removing proteolytic fragments, solving protein structure and/or protein folding complexities, and ensuring the safe removal of toxins from final products.
Conventional solutions sometimes fall short
The conventional response to problems of this kind might be to call in a contract manufacturing organisation (CMO) or specialist consultancy for technical support. However, the limited capabilities of standard manufacturing methodologies often fall short. Processing engineering is an expensive exercise, and sometimes, no amount of engineering can overcome the challenges faced. For certain technical challenges, only biology can provide the solution to recombinant protein problems, and upstream biology frequently helps address engineering issues, not the other way around.
Many businesses apply process engineering to resolve their manufacturing problems, but this carries risks, and there is a ceiling on what it can deliver. For example, suppose the upstream biology is the cause of downstream processing issues, leading to losses from processing and/or purification that substantially reduce net yield. In that case, this can lead to projects stalling or being unviable.
A better approach
Fortunately, new technology already exists that enables us to unlock the full power of biology to resolve a whole range of previously intractable technical problems. Quantitative Trait Loci (QTL) technology works by generating manufacturing strains that are optimised for the specific requirements of your project. This enables genuine multi-parameter optimisation of the production host for any phenotypes affecting the process, not just product titre.
Using this new approach to recombinant protein manufacture, your project’s issues are analysed to guide a custom solution. This analysis enables us to generate and screen for the manufacturing strains improved for the protein and process facility and then gain a detailed understanding of the regions and variations of the genome involved.
On this basis, Phenotypeca deploys its expertise in breeding diverse strains to establish what biology can deliver naturally, while avoiding the functional limitations and ‘sick’ strains associated with previous methods such as mutagenesis. The dexterity of QTL technology gives far greater scope for problem-solving than conventional strain engineering, which is usually constrained to engineering a single genomic chassis, along with relatively limited genome knowledge and dexterity.
Benefits of QTL
QTL technology has already demonstrated its ability to remove technical roadblocks from promising projects – and make them viable again. It can further improve the profitability of existing products and develop new uses to access new markets, and shelved projects can be resurrected using QTL-optimised production strains.