“No technical limits for utilization of affinity based purification methods”

Interview with Prof. Sophia Hober, KTH Royal Institute of Technology, Stockholm, 9th August

What is the impact of engineered affinity proteins on biomedicine? Are there affinity proteins approved as therapeutics?

"The area of affinity based therapeutics are dominated by monoclonal antibodies, with a long track record of efficient treatment within different therapeutic areas and importantly, the antibody scaffold is tolerated by the human body. In order to develop alternative affinity therapeutics it has to come with advantages in comparison with the commonly used mAB scaffold. Two important advantages with many of the smaller versions of affinity proteins are, less expensive production and more efficient tissue penetration. Currently there are only a hand full engineered affinity proteins that are approved as therapeutics, but to date there are many variants under way in different stages of clinical trials."

Where are the limits for the scale-up of biotechnological separations with affinity proteins?

"The most exploited group of chromatography matrix based on protein affinity, is utilizing different versions of protein A. These matrices are the core in most industrial purifications of monoclonal antibodies. Hence, I don’t think that there are any technical limits for utilization of affinity based purification methods. However, if the matrices can´t withstand  the harsh CIP treatment needed between batches, and thereby constraining the number of times the matrix can be used, the price for the matrix might set the limit."

How does the current progress in computational modelling change protein engineering?

"The progress in computational modelling definitely have a big impact on the development of binders. Although it still is a challenge to exactly predict a good binder, there are features that could be of great help, like suggesting what residues to randomize, predict stability and suggest changes to improve the affinity. During the coming years, I think that this field will progress even more and thereby be even more useful within this area."

Which advancements do you expect with regards to the biological production systems of recombinant (affinity) proteins?

"Within the field of protein production, there are many different areas with a lot of focus on the efficiency in the production step. Although the production levels normally are very high for many target proteins, there are challenges regarding production of specific proteins. Here we need to understand where the differences comes from and map the cell specific proteins that are important for the expression efficacy, but also what is needed for efficient folding and secretion."

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