MIT engineers have found an inexpensive way to manufacture protein drugs like insulin or antibodies. They have improvised the purification step, which involves isolating the protein from the bioreactor used to produce it; this step accounts for up to half of the total cost of manufacturing a protein.
The new method or approach uses specialized nanoparticles to rapidly crystallize proteins. It can help make protein drugs more affordable and accessible. Kripa Varanasi, a professor of mechanical engineering at MIT and the senior author of the new study, said the new method uses bioconjugate-functionalized nanoparticles to act as templates for enhancing protein crystal formation at low concentrations. “The goal is to reduce the cost so that this kind of drug manufacturing becomes affordable in the developing world.”
It can be used to crystallize Iysozyme (an antimicrobial enzyme) and insulin. The researchers believe the new method can be applied to many other useful proteins, including antibody drugs and vaccines. They decided to work on the new method based on protein crystallization. However, many scientists regard this process as too slow for industrial use as it doesn’t work well at low concentrations of protein.
Varanasi’s lab overcame these obstacles by using nanoscale structures to speed up crystallization. The lab had previously uses nanoscale features to create materials that repel water or to modify interfaces for injecting highly viscous biologic drugs. The researchers wanted to use nanoparticles to locally boost the concentration of protein at the surface. They wanted to provide a template that would allow the proteins to align correctly and form crystals.
As such, the researchers coated gold nanoparticles with molecules called bioconjugates (materials that can help form links between other molecules). They used bioconjugates called maleimide and NHS, which are commonly used for tagging proteins for study or attaching protein drugs to drug-delivering nanoparticles. The proteins accumulate at the surface when they are exposed to these coated nanoparticles and bind to the bioconjugates.
The bioconjugates prompt the proteins to align themselves with a specific orientation, creating a scaffold for additional proteins to join the crystal. Varanasi explained that this general approach could be scaled to other systems. “If you know the protein structure that you’re trying to crystallize, you can then add the right bioconjugates that will force this process to happen.”
The researchers also established that crystallization occurred much faster when the proteins were exposed to the bioconjugate-coated nanoparticles – compared to the bare nanoparticles, or no nanoparticles.