Abstract:
:The understanding of how cellular productivity is modulated in cell lines is of significant importance in the biopharmaceutical industry. Often, single molecular mechanisms fail to fully explain how specific antibody productivity is enhanced during proliferation arrest. Previously, we reported that certain physiological changes occur when proliferation is arrested by p21(CIP1) over expression. In this work, we correlate physiological and molecular factors to enhance antibody productivity. Using biomass, cell volume and total cellular protein content as a basis for determining specific productivity, it was found that total cellular protein correlated best with cellular productivity. This meant that there was no preferential increase in antibody production relative to cellular proteins in arrested cultures. However, molecular analysis of mRNA transcription and stability indicated that both processes were altered in arrested cultures resulting in up to threefold increased heavy chain mRNA levels. While flow cytometric analysis revealed that arrested cells had elevated translational capacity for both heavy and light chains, the heavy to light chain polypeptide ratio was 10-50% higher than in the control. This resulted in a lower extracellular accumulation of light chains and a better utilization of cellular resources for the formation of complete antibodies. Active transcriptional regulation of heavy and light chain mRNA and the modulation of translational activities play a vital role in the modulation of overall antibody productivity of these cells. The combined effect of heavy chain mRNA enhancement and the increased cellular assembly capacity was determined to effectively increase specific productivity.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Khoo SH,Al-Rubeai Mdoi
10.1002/bit.22041subject
Has Abstractpub_date
2009-01-01 00:00:00pages
188-99issue
1eissn
0006-3592issn
1097-0290journal_volume
102pub_type
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