Kerstin Otte
University of Applied Sciences Biberach, Germany
Title: Synthetic microRNAs to boost cellular production of biopharmaceuticals
Biography
Biography: Kerstin Otte
Abstract
Recently, microRNAs (miRNAs) have been discovered as innovative instruments for cell engineering of biopharmaceutical production cells to minimize existing bottlenecks of eukaryotic expression systems. As small non-coding RNAs, miRNAs do not add any translational burden to the cell and several miRNAs can be exploited in parallel as polycystronic clusters thereby acting concertedly to regulate hundreds of different target genes and regulate entire pathways within the cell. miRNAs are involved in virtually all cellular processes such as apoptosis, proliferation, development or protein biosynthesis. The revelation of the Chinese hamster ovary (CHO) genome and transcriptome as well as the CHO miRnome substantially accelerated miRNA research in this industrially relevant cell type. To elucidate miRNA function and usability as engineering tools in recombinant CHO cells, we performed a genome-wide high-content miRNA screen assaying for phenotypic changes regarding productivity, cell proliferation, viability, necrosis and apoptosis. Among many novel ‘engimiRs’ which have been found within the screen we discovered a whole miRNA family to strongly contribute to enhanced protein production in CHO cells. Stable overexpression gave rise to superior cell lines outperforming the parental cell line. Moreover, detailed analysis of screening data revealed a novel redundant mechanism of action for miRNAs in eukaryotic cell systems. Our results highlight the application of miRNAs as powerful tools for cell engineering and will shed additional light on these tiny but mighty regulators of gene expression.