Biotherapeutic proteins manufactured in cell culture systems have transformed modern medicine. Selling many tens of billions per year, new biotherapeutics such as monoclonal antibodies have delivered dramatic clinical results, while posing significant manufacturing problems.: During the cell culture manufacturing process, toxic bioproducts such as lactate and ammonia have posed considerable challenges in bioprocessing, since they limit cell growth and impact critical quality attributes of recombinant protein production (e.g., therapeutic drugs, enzymes). That is because the lactate alters the regulation of biosynthetic enzymes, and can lead to changes in pH in the culture. To mitigate the negative effects of lactic acid accumulation and control the culture pH, chemical ‘base’ is added to the media during the course of a bioprocess. However, the base addition negatively impacts the bioprocess by inhibiting growth and shortening the length of time in which the cells can produce the recombinant protein. This leads to reduced yield, and increased cost-of-goods. Thus, it is of great interest to eliminate lactate production, and UC San Diego researchers have recently developed a new process for achieving this.
UC San Diego researchers have developed a patent-pending technology that addresses this need by demonstrating a method to completely eliminate lactate production via a homozygous knockout of lactate dehydrogenase. The method (and resultant cell line) will be invaluable to companies using mammalian cells for biotherapeutic protein production, as it represents a simple way to increase protein production, directly affecting biotherapeutic product cost-of-goods
|United States Of America||Published Application||2019-0256824||08/22/2019||2016-222|
Biotherapeutics, cell culture, biomanufacturing, process optimization