Protein processing specialist Novexin Ltd (Cambridge, UK) has developed a new technique to improve yields from protein refolding processes. The patented technology, which was first made available to industry this summer, is currently in use at many large pharmaceutical and biotechnology groups.
"We developed the technology from the standpoint of knowing that there’s always been a problem with the methods,” explains Paul Docherty, PhD, sales and marketing manager for Novexin. The challenge, says Docherty, has been generating consistent protein yields without using time-consuming or expensive processes. “Instead of going down a laborious screening approach, you can use this one technique for all classes of proteins. In that respect, it’s chaperone-like in the way it works,” says Dochert.
The technology stabilizes unfolded protein, prevents aggregation, and allows the refolding process to take place under controlled conditions.To run the two-day procedure, scientists conduct a normal dilution refold using the Novexin reagents. The reagent binds to the protein and protects it during the refolding process, which reduces yield loss caused by aggregation. Without this protection, the proteins aggregate irreversibly during refolding and become inactive. Then, a release step separates the reagent and protein. “It’s structured so you have very tight control over that release. It’s that slow release that favors the refold to an active protein,” notes Docherty. Because the process does not use detergents, it is suitable for large-scale protein production.
According to Novexin, a key advantage of the technique is that it quickly generates clear yes–no answers about refolding success. Says Docherty, "It's decision-making data. If you get good results with us, you know you can progress further. If you get low results, drop the project. You’ll never refold it.”
The company hopes the technology will enable researchers to readopt dropped projects, such as those using E. coli, that were deemed too expensive or inefficient to pursue.