Purification, or isolating the protein from the bioreactor that produced it, is one of the most expensive procedures in the production of protein drugs like insulin or antibodies. This process may cost as much as half of the overall price of producing a protein.

Now, MIT engineers have developed a novel technique for carrying out this type of filtration to lower production costs.

Their method, which quickly crystallizes proteins using specialized nanoparticles, may make protein drugs more affordable and available, particularly in underdeveloped nations.

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Novel Method

"This work uses bioconjugate-functionalized nanoparticles to act as templates for enhancing protein crystal formation at low concentrations," Kripa Varanasi, senior author of the study, said in a press release statement.

"The goal is to reduce the cost so that this kind of drug manufacturing becomes affordable in the developing world."

The scientists showed that their method may be used to crystallize insulin and the antibacterial enzyme lysozyme. They believe that it might be used for other beneficial proteins, such as vaccinations and antibody-based medications.

A family of medications known as biologics, which also includes molecules like DNA and RNA and cell-based therapies, includes antibodies and other protein-based medications.

In massive bioreactors, live cells like yeast manufacture the majority of protein medications.

After these proteins are produced, they must be separated from the reactor, which is typically accomplished through a procedure known as chromatography. 

Chromatography, which divides proteins according to their size, needs specific materials, which raises the cost of the procedure significantly.

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Alternative Strategy

The alternative strategy, based on protein crystallization, was chosen by Varanasi and his colleagues. Proteins are frequently crystallized by researchers to analyze their structures, however, the procedure is deemed too laborious for industrial application and is ineffective at low protein concentrations.

Varanasi's lab set out to use nanoscale structures to hasten crystallization to get around those challenges.

The goal was to modify nanoparticles to boost the protein concentration at the surface locally and to act as a template for the proteins' proper alignment and crystallization.

The scientists covered gold nanoparticles with bioconjugates, chemicals that can assist in forming bonds between other molecules to generate the surface that they require. 

Maleimide and NHS bioconjugates, which are frequently used to tag proteins for research or affix protein medicines to drug-delivery nanoparticles, were utilized by the researchers for this work.

The scientists used the enzyme lysozyme, whose crystallization characteristics have been extensively researched, and insulin to show their methodology. 

The researchers found that the proteins crystallized far more quickly when exposed to bioconjugate-coated nanoparticles as opposed to bare nanoparticles or no nanoparticles.

The MIT team is now focused on scaling up the procedure so that it can be applied in an industrial bioreactor and can be used to produce monoclonal antibodies, vaccines, and other valuable proteins.

The study was published in  the journal ACS Applied Materials and Interfaces.

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