The Chinese hamster ovary cell (CHO) has been the “work horse” of the biopharmaceutical industry for the past 2 decades. Their preeminent position is due to their genetic tractability and capacity to produce high quality recombinant proteins with human-like post-translational modifications. Productivity limitations, however, have stimulated the application of various optimisation strategies to further improve therapeutic product yields. Despite the marked improvements in bioprocess design and media formulation, enhanced CHO cell performance is by no means routine. microRNAs (miRNAs) offer an attractive alternative to genetic engineering using a protein-coding gene due to their ability to regulate multiple molecular networks simultaneously in addition to reducing the cells translational burden. Our lab identified various miRNAs whose expression was closely correlated with CHO cell growth rate including the oncogenic miR-17~92 cluster and the ribosome-enhancing miR-10a, as well as various growth-associated miRNAs such as miR-30e, miR-206, miR-451 and miR-639. Transient characterisation of a set of these candidates revealed several to negatively regulate growth and apoptosis such as miR-34a/34a* and miR-23b*; positively influence growth including miR-15a-16-1 and miR-532-5p and potentially enhance specific productivity in the case of miR-200a. CHO clones with enhanced growth attributes could achieve high cell densities early in culture prior to the induction of a temperature-shift, a process control strategy commonly used to enhance specific productivity but often at the cost of growth. A common trade-off for enhanced growth is often the reduction in CHO cell specific productivity. Stable depletion of miR-23, implicated in B-cell differentiation, using a miR-sponge decoy was observed to enhance recombinant protein yield by ~3-fold without influencing CHO-SEAP cell growth in batch culture. Interestingly, these high producing clones also demonstrated a ~30% increase in oxidative metabolism, an energy state previously associated with productivity. The mitochondrial electron transport system components, Complex I and II, were observed to be responsible for this enhanced energy provision. Proteomic analysis identified potential targets of miR-23 involved in the TCA cycle e.g. IDH1 and MDHA/B and related to mitochondrial function e.g. LETM1. Process adaptation to complement inherent clonal attributes can be exploited to enhance production yields as evident in the case of a miR-23b*-depleted clone achieving a 50% improved SEAP yield in a fed-batch culture with temperature shift (31°C). Exploiting the role of miRNAs in the regulation of bioprocess-related phenotypes (e.g. miR-34a and its role in antibody fucosylation) highlights the versatility of these small molecules for industrial application, a prospect further explored within this thesis.