New Strategies for Downstream Processing of Recombinant Proteins

Feasibility study offers the potential to improve the production of therapeutic proteins.

Challenge

Protein purification is a multi-step process which is time consuming, expensive and usually needs to be tailored to each protein of interest.

This project investigated whether a generally applicable, platform procedure could be established using small protein tags attached to the protein of interest, which could be captured by affinity binding to a resin which had been previously functionalised with a peptide to which the protein tag can bind.

Solution

FUJIFILM Diosynth Biotechnologies UK worked with Lynne Regan’s group at the University of Edinburgh.

FDB UK provided guidance, including advice on industrially relevant proteins which could be used as models to demonstrate the technology. FDB UK also hosted a Post Doctoral Research Associate in their process development facilities in Billingham to test the new technology.

Lynne Regan’s group designed and produced the affinity protein tag/peptide pairings. The peptide ligand was then attached to a resin and the functionalised resin was shown to be stable to cleaning with sodium hydroxide, a critically important feature for use in a GMP environment. Several tagged, industrially relevant, proteins were then shown to bind with good affinity to the ligand and were successfully purified. The robustness of the purification process was evaluated under different pH conditions and the binding capacity of the affinity resin determined for different proteins.

Outcome

The project was able to demonstrate successful purification of several industrially relevant proteins proving that the developed protein tag-ligand pairing technology works as intended.

This successful proof of concept study means that with further development the affinity purification process could be applied at FDB UK, potentially delivering significant savings in terms of process time and costs.