Customize Solution for Refolding of Biotherapeutic Protein | Rashmi Sharma

Interview

How would you explain your research outcomes to the non-scientific community?

Proteins are widely known for their functions in our body. These functions are generally the boon of their specific 3D structure in space (cells, solutions etc) called the ‘native structure’. Therefore, when cells make proteins, they are ‘folded’ to the correct form before being employed. Hence, the structure is extremely important and any change/s in it can render the protein useless or even toxic.?

A variety of protein manufacturing processes have steps dedicated for the conversion of the proteins to their native, functional 3D states, before being processed further for consumption. This step is called the ‘Refolding step’, wherein a mis-folded protein is re-folded to correct shape. Specific chemicals and treatments are provided to the molecules to change their structures in the desired way. However, it is a very dynamic and sensitive reaction. Most of the protein is lost in misfolded states due to the complex folding pathway and incompetent chemical/physical environment. The refolding step is therefore dubbed as a bottleneck. The expensive chemicals and large amount of time add to the complexity.?

Scanty information about the detailed folding steps in the reaction fails the researchers to produce appropriate refolding schemes.

The aim of our study was to analyse the details of the folding pathway of a biotherapeutic protein called ‘Ranibizumab’. It is used to treat age related macular degeneration (AMD) which leads to vision loss. We looked at the pathway using various sophisticated analytical tools which led us to decipher part of the process. We were able to dissect the process in two parts, where initial stages supported correct bond formation while the later stages corresponded to correct rearrangements of the bonds and shape.?

This information was used to tailor suitable chemicals and precise physical (temperature, pH, time etc) set points for the different stages. We then compared this refolding scheme to a ‘conventional’ generic hit-and-trail approach and a significant increment (55%) was observed.

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