Engineering the HEK293 cell line for improved culture performance. In targeted engineering, genes involved in processes directly affecting protein expression such as apoptosis, cell proliferation, central carbon metabolism, glycosylation, protein folding, and secretion are modified. Global engineering encompasses high throughput screens using RNA interference (miRNA and siRNA), Zinc Finger protein transcription factor libraries, and CRISPR/Cas 9 libraries, and omics analysis such as transcriptomic, proteomic, metabolomic, and fluxomic analyses that are utilized to discover novel engineering targets.