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The marine diatom Phaeodactylum tricornutum is currently used for various industrial applications, including the pharmaceutical industry as a cost-effective cell biofactory to produce Biologics. Recent studies demonstrated that P. tricornutum can produce functional monoclonal antibodies, such application is currently limited by the production yield that hinders industrialization. Therefore, it is necessary to understand and control the cell biology of P. tricornutum to improve the Biologics production yield. Transcriptomic analyses have recently been used by the pharmaceutical industry to improve the production of Biologics in mammalian cells, especially Biologics titer and cell productivity. Hence, in the present work, we performed a meta-analysis of seven publicly available RNA-Seq datasets from different strains of P. tricornutum, for which the culture conditions were chosen as similar as possible. We analyzed the differential expression of genes that are involved in biological processes that are well known to potentially impact the bioproduction and critical quality attributes of Biologics. Therefore, the expression of genes involved in the N-glycan biosynthesis, protein export and secretion, protein quality control and proteasome, as well as those encoding proteases were analyzed and compared. The results pave the way towards optimizing Biologics production in P. tricornutum and highlight that the Pt4, Pt3 Ov and Pt8 strains seem to be the most promising P. tricornutum strains. [ABSTRACT FROM AUTHOR]

The production of biologics in mammalian cells is hindered by some limitations including high production costs, prompting the exploration of other alternative expression systems that are cheaper and sustainable like microalgae. Successful productions of biologics such as monoclonal antibodies have already been demonstrated in the diatom Phaeodactylum tricornutum; however, limited production yields still remain compared to mammalian cells. Therefore, efforts are needed to make this microalga more competitive as a cell biofactory. Among the seventeen reported accessions of P. tricornutum, ten have been mainly studied so far. Among them, some have already been used to produce high-value-added molecules such as biologics. The use of "omics" is increasingly being described as useful for the improvement of both upstream and downstream steps in bioprocesses using mammalian cells. Therefore, in this context, we performed an RNA-Seq analysis of the ten most used P. tricornutum accessions (Pt1 to Pt10) and deciphered the differential gene expression in pathways that could affect bioproduction of biologics in P. tricornutum. Our results highlighted the benefits of certain accessions such as Pt9 or Pt4 for the production of biologics. Indeed, these accessions seem to be more advantageous. Moreover, these results contribute to a better understanding of the molecular and cellular biology of P. tricornutum. [ABSTRACT FROM AUTHOR]