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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\u201026a\u20105p and miR\u2010337\u20105p, that increased human IgG1 (huIgG1) yields by 50 and 25%, respectively. The titer increase was achievable by expressing miR\u201026a\u20105p from oligonucleotides or a plasmid. Furthermore, combining miR\u201026a\u20105p with valproic acid (VPA) treatment doubled huIgG1 titers. Assessment of miR\u201026a\u20105p and VPA treatment across a panel of 32 human and murine antibodies demonstrates that the level of yield enhancement was molecule\u2010dependent, with most exhibiting a range of 50\u2013100% titer increase. These findings exemplify that combining genetic and chemical manipulation can be an effective strategy to enhance transient transfection productivity. \u00a9 2017 American Institute of Chemical Engineers <jats:italic>Biotechnol. 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