Global demand for biopharmaceuticals is increasing and requires constant improvement in manufacturing processes. Chinese hamster ovary (CHO) cells are dominant host for production of recombinant therapeutic proteins with human-like post-translational modifications. In the past, engineering of mammalian cell systems was focused on the manipulation of single target genes or proteins. Although cell performance is enhanced, numerous limitations and bottlenecks remain. Therefore, novel technologies and improvements in biopharmaceutical manufacturing processes are necessary to address this issue. Several unique characteristics make microRNAs (miRNAs) attractive alternative for CHO cell engineering. MicroRNAs are small non-coding RNAs that regulate gene expression at post-transcriptional level. Mature miRNA can simultaneously repress or degrade multiple target mRNAs involved in many cellular processes such as proliferation, apoptosis, cell cycle, metabolism, and protein synthesis. Importantly, mature miRNAs are highly conserved between species and due to low-target-specificity, they are capable of regulating hundreds of genes. Hence, several reports showed successful application of miRNA (engimiR) in CHO optimizations. However, due to insufficient improvement and cell line or recombinant protein dependency, none of them have made their way into industrial setting. The goal of this thesis was to explore phenotypic change after transient transfection with miRNA and identify engimiRs that improve CHO cell-specific productivity and viable cell concentration (VCC). Following protocol set-up, successful transfection of CHO cell line expressing recombinant erythropoietin (rEPO) with five pre-selected miRNAs confirmed proof-of-principle. Cell counting and ELISA assay provided insight into the effect of miRNA transfection on the VCC and rEPO concentration. In addition, functional high-throughput miRNA screening of non-viral delivery of human miRNA mimics library to CHO-rEPO was employed. Using this approach, 26 from 2042 miRNAs were identified to improve rEPO concentration at the cellular level by 3.5 to 6.0-fold without decreasing VCC. Highest effect, 6-fold increase in cell-specific productivity was detected after transient transfection with miR-3153. Finally, bioinformatics tools miRBase and miRWalk were utilized to predict conservation of human miRNA in CHO cells and to identify potential targets. Further studies are necessary in order to validate results and to select cell line and protein independent engimiRs in large-scale production.