Identification of a novel miRNA that increases transient protein expression in combination with valproic acid.

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.