The mammalian cell lines that are engineered to produce high-value recombinant-protein drugs also produce unwanted proteins that push up the overall cost to manufacture these drugs. These same proteins can also lower drug quality. In a new paper in Nature Communications, researchers from the University of California San Diego and the Technical University of Denmark showed that their genome-editing techniques could eliminate up to 70 percent of the contaminating protein by mass in recombinant-protein drugs produced by the workhorses of mammalian cells—Chinese Hamster Ovary (CHO) cells.
With the team's CRISPR-Cas mediated gene editing approach, the researchers demonstrate a significant decrease in purification demands across the mammalian cell lines they investigated. This work could lead to both lower production costs and higher quality drugs.
Recombinant proteins currently account for the majority of the top drugs by sales, including drugs for treating complex diseases ranging from arthritis to cancer and even combating infectious diseases such as COVID-19 by neutralizing antibodies. However, the cost of these drugs puts them out of reach of much of the world population. The high cost is due in part to the fact that they are produced in cultured cells in the laboratory. One of the major costs is purification of these drugs, which can account for up to 80 percent of the manufacturing costs.
In an international collaboration, researchers at the University of California San Diego and the Technical University of Denmark recently demonstrated the potential to protect the quality of recombinant protein drugs while substantially increasing their purity prior to purification, as reported in the study entitled "Multiplex secretome engineering enhances recombinant protein production and purity" published in April 2020 in the journal Nature Communications.
"Cells, such as Chinese hamster ovary (CHO) cells, are cultured and used to produce many leading drugs," explained Nathan E. Lewis, Associate Professor of Pediatrics and Bioengineering at the University of California San Diego, and Co-Director of the CHO Systems Biology Center at UC San Diego. "However, in addition to the medications we want, the cells also produce and secrete at least hundreds of their own proteins into the broth. The problem is that some of these proteins can degrade the quality of the drugs or could elicit negative side effects in a patient. That's why there are such strict rules for purification, since we want the safest and most effective medications possible."