Scientific Publications by FDA Staff

Biotechnol Prog 2012 Sep;28(5):1126-37

Genomic analysis of a hybridoma batch cell culture metabolic status in a standard laboratory 5 L bioreactor.

Kondragunta B, Han J, Joshi BH, Brorson KA, Puri RK, Uplekar S, Moreira AR, Rao G

Currently, there is a gap in the knowledge of the culture responses to controlled bioreactor environment during the course of batch cell culture from early exponential phase to stationary-phase. If available, such information could be used to designate gene transcripts for predicting cell status and as a quality predictor for in a controlled bioreactor. In this study we used microarrays to obtain baseline gene expression profiles during the time-course of a hybridoma batch cell culture in a 5 L bench-scale bioreactor. Gene expression profiles that were up or down modulated from early-to-late in batch culture, as well as invariant gene profiles with significant expression were identified using microarray. Typical cellular functions that seemed to be correlated with transcriptomics were oxidative stress response, DNA damage response, apoptosis, and cellular metabolism. As confirmatory evidence, microarray findings were verified with a more rigorous semi-quantitative gene-specific RT-PCR. The results of this study suggest that under predefined bioreactor culture conditions, significant gene changes from lag to log to stationary phase could be identified, which could then be used to track the culture state.