Table 2.
Genes that have been engineered to modulate proliferation in the HEK293 cell line.
| Gene | Function | Modification | Outcome | Recombinant Protein(s) | Reference |
|---|---|---|---|---|---|
| Cyclin-dependent kinase like 3 (CDKL3) | Promotes cell cycle G1-S transition in mammalian cells | Overexpression | 19% improvement in growth rate, 20% improvement in r. protein production, 8% greater maximum viable cell density | Secreted recombinant adipocyte complement-related protein of 30kDa | [56] |
| Cytochrome c oxidase subunit 15 (COX15) | Counteracts apoptosis due to its involvement in the Synthesis of heme | 13% improvement in growth rate and 11% improvement in r. protein production | |||
| Eukaryotic initiation factor 3 subunit i (EIF3I) | Subunit of the eIF3 targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation, and apoptosis. | Overexpression | Faster growth and increased c-Myc expression. | Renilla and Firefly luciferase | [57] |
| Cyclin-dependent kinase inhibitor 1B (CDKN1B) | Binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1 | Inducible over-expression | 5.9-fold increase in recombinant protein expression | Recombinant secreted alkaline phosphatase (SEAP) | [59] |
| Cyclin-dependent kinase inhibitor 1A (CDKN1A) | Binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1 | Overexpression (Coupled with rational vector design and valporic acid treatment) |
Approximately 27-fold increase in recombinant protein production, from 40 mg/L to 1.1 g/L in transient system | IgG | [58] |
| Cyclin-dependent Kinase inhibitor 2C (CDKN2C) | Interacts with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus functioning as a cell growth regulator that controls cell cycle G1 progression | ||||
| Acidic fibroblast growth factor (FGF1) | Involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion |