Abstract
Transient gene expression in mammalian cells is an efficient process to produce recombinant proteins for various research applications and large molecule therapeutics development. For the first time, we report a screen to identify human microRNAs (miRNAs) that increase titers after polyethylenimine (PEI) mediated transient transfection of a HEK293 cell line. From a library of 875 miRNAs, we identified 2 miRNAs, miR-26a-5p and miR-337-5p, that increased human IgG1 (huIgG1) yields by 50 and 25%, respectively. The titer increase was achievable by expressing miR-26a-5p from oligonucleotides or a plasmid. Furthermore, combining miR-26a-5p with valproic acid (VPA) treatment doubled huIgG1 titers. Assessment of miR-26a-5p and VPA treatment across a panel of 32 human and murine antibodies demonstrates that the level of yield enhancement was molecule-dependent, with most exhibiting a range of 50-100% titer increase. These findings exemplify that combining genetic and chemical manipulation can be an effective strategy to enhance transient transfection productivity. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1139-1145, 2017.
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