6. Controlled switch to high qP phenotype

Plasma cells, as the bodies own antibody factory, typically have a specific productivity of between 150 and 200pg/c/d. Production cell lines range between 20-50 pg/c/d. However, plasma cells undergo a significant rearrangement of their cellular composition and machinery before starting such high productivity and they typically can not resume growth and die within 14 days. It is likely that such high productivities are prohibitive for growth and survival. Thus this phenotypic switch would only be an appropriate tool in bioprocesses if it is designed as a transient phase to be achieved only towards the end of a process to increase the yield. The transcription factors and microRNAs that control the transition from a B cell to a plasma cell are well described and know. Thus such a switch in cellular phenotype could be achieved by two routes: controlled expression of the required factors using a promoter as described in 5, or addition of these factors at defined culture points to induce the phenotypic switch to high qP.

Approaches:

  • Testing of ability of CHO cells to achieve a plasma cell transition using transient transcription of the described transcription factors and microRNAs
  • Evaluation of methods to achieve this by addition of required factors
  • Evaluation of possibility to engineer cells


Target: Controlled switch to high qP phenotype at defined time point in bioprocesses