Apoptosis Pathways

Commercial mammalian cell culture occurs in bioreactors, where cells can experience a number of stresses such as nutrient depletion, growth factor deprivation, and byproduct accumulation. These stresses, if severe enough, can lead to the activation of a cell suicide program called apoptosis. Premature cell death by apoptosis accounts for upwards of 80% of cell death in culture and can lead to decreased product yields, compromised product quality, and increased cost of downstream processing.

Some of the major proteins involved in apoptosis belong to the Bcl-2 (B-cell lymphoma) family of protein, which contains both pro- and anti-apoptotic molecules. Using recombinant DNA technology, we can express anti-apoptotic Bcl-2 proteins in commercially-relevant mammalian cells. Expression of these anti-apoptotic proteins can lead to cultures with higher viability and increased production of recombinant therapeutics, resulting in decreased production costs.

References

Krambeck, Frederick J., Sandra V. Bennun, Someet Narang, Sean Choi, Kevin J. Yarema, and Michael J. Betenbaugh. "A Mathematical Model to Derive N-Glycan Structures and Cellular Enzyme Activities from Mass Spectrometric Data." Glycobiology 19, no. 11 (November 01, 2009): 1163-1175.