Breaking virus-like particles (VLPs) into smaller subunits and then reassembling them afterwards can solve many of the traditional problems with manufacturing them. That’s the message of a talk by an Australian scientist earlier this year. Lukas Gerstweiler, PhD, a lecturer at the University of Adelaide, says breaking up VLPs for manufacture can also allow them to be manufactured using continuous processing techniques, increasing both performance and yields.
“My main message is lots of research has focused on the struggle to make VLPs in useful quantities and how the quality is bad. However, I believe I’ve now shown that it’s possible to produce a large amount using a fully scalable process,” he continues. “This can potentially make VLP production much cheaper, turning VLPs into a viable class of products with applications ranging from drug carriers to a platform technology for vaccines.”
According to Gerstweiler, VLP manufacturing traditionally has poor yields using standard techniques optimized for antibody purification, such as chromatography, because they’re large compared to traditional recombinant proteins. As he explains, VLPs can be 50 nm in size compared to 4–5 nm for an antibody, meaning they can’t enter the pores of chromatography resins.
Alternatively, he points out, they can become trapped in the pores of the membranes used for filtering out product. In addition, because VLPs are hollow and shaped like soccer balls, the void in the center can easily become filled with impurities and contaminants, which are hard to remove.
To get around this problem, Gerstweiler used Dithiothreitol (DTT) to weaken bonds and break the VLP into subunits before purification. After purifying the subunits, he changed the buffer composition, and they reassembled into VLPs.
One of the benefits of his purification process, he says, was that he could use a multi-column system to run it continuously. By connecting two columns together, Gerstweiler could reduce the buffer consumption needed and prevent oversaturation of the filters, increasing the productivity and reducing buffer costs.
“This a powerful tool for continuous processing, which was originally developed for mAbs,” he says. “By using it on VLPs, you achieve all the benefits of continuous processing, including higher productivities, lower costs, and the removal of batch-to-batch variations.”
He hopes the new process will open up new applications and pathways for developing VLPs.
The post Benefits of Breaking Up Virus-Like Particles for Biomanufacturing appeared first on GEN - Genetic Engineering and Biotechnology News.
“My main message is lots of research has focused on the struggle to make VLPs in useful quantities and how the quality is bad. However, I believe I’ve now shown that it’s possible to produce a large amount using a fully scalable process,” he continues. “This can potentially make VLP production much cheaper, turning VLPs into a viable class of products with applications ranging from drug carriers to a platform technology for vaccines.”
According to Gerstweiler, VLP manufacturing traditionally has poor yields using standard techniques optimized for antibody purification, such as chromatography, because they’re large compared to traditional recombinant proteins. As he explains, VLPs can be 50 nm in size compared to 4–5 nm for an antibody, meaning they can’t enter the pores of chromatography resins.
Weakening bonds
Alternatively, he points out, they can become trapped in the pores of the membranes used for filtering out product. In addition, because VLPs are hollow and shaped like soccer balls, the void in the center can easily become filled with impurities and contaminants, which are hard to remove.
To get around this problem, Gerstweiler used Dithiothreitol (DTT) to weaken bonds and break the VLP into subunits before purification. After purifying the subunits, he changed the buffer composition, and they reassembled into VLPs.
One of the benefits of his purification process, he says, was that he could use a multi-column system to run it continuously. By connecting two columns together, Gerstweiler could reduce the buffer consumption needed and prevent oversaturation of the filters, increasing the productivity and reducing buffer costs.
“This a powerful tool for continuous processing, which was originally developed for mAbs,” he says. “By using it on VLPs, you achieve all the benefits of continuous processing, including higher productivities, lower costs, and the removal of batch-to-batch variations.”
He hopes the new process will open up new applications and pathways for developing VLPs.
The post Benefits of Breaking Up Virus-Like Particles for Biomanufacturing appeared first on GEN - Genetic Engineering and Biotechnology News.