How can genetic engineering be used to enhance workflows for biologics production?
The other major role for genetic engineering in biologics production is to augment existing functionality – in particular, augmenting the production capacity of cellular factories. For a cellular factory, production capacity is determined by a combination of metabolic and genetic factors. Metabolic factors include the propensity of a cell to enter apoptosis, the endogenous presence of any enzymes or factors that can degrade/alter the final product, and cellular sensitivity to changes in culture environment conditions (i.e., crowding, media composition).1 Genetic factors generally impact susceptibility to transfection and transduction as well as transgene stability.2
Genetic engineering can alleviate the problems caused by both metabolic and genetic factors. The insertion of anti-apoptotic and pro-growth genes has been documented to improve cell longevity and productivity.1,3 Similarly, inserting genes encoding proteins which naturally consume cellular waste products or knocking down waste product-related genes has also aided cellular viability and productivity.1,2 Researchers have even been able to improve the structural consistency and quality of the final product by inserting genes encoding enzymes capable of making targeted structural alterations into cells that do not normally express them.1
(1) F.M. Wurm, “Production of recombinant protein therapeutics in cultivated mammalian cells,” Nat Biotechnol, 22(11):1393-1398, 2004.
(2) H. Waegeman and W. Soetaert, “Increasing recombinant protein production in Escherichia coli through metabolic and genetic engineering,” J Ind Microbiol Biotechnol, 38(12):1891-1910, 2011.
(3) K. Sunley and M. Butler, “Strategies for the enhancement of recombinant protein production from mammalian cells by growth arrest,” Biotechnol Adv, 28(3):385-394, 2010.