Table 3.

Genes that have been engineered to delay apoptosis in the HEK293 cell line.

Gene	Function	Modification	Outcome	Recombinant Protein(s)	Reference
X-linked inhibitor of apoptosis (XIAP)	Inhibits the apoptosis executioners caspase3, caspase 7, and caspase 9	Overexpression	8-fold higher number of viable cells., extension of stationary phase by 48 h	N/A	[62] [63]
B-cell lymphoma 2 (BCL2)	Inhibits the pro-apoptotic proteins Bak and Bax	Overexpression Over-expression	Extension of stationary phase by 48 h 53% increase in volumetric production	N/A Lentiviral vectors	[63] [66]
Caspase 3 (CASP3) , Caspase 6 (CASP6) , Caspase 7 (CASP7) and Allograft inflammatory factor 1 (AIF1)	Executioners of apoptosis in the caspase dependent pathway	Quadruple Knockout	Higher expression levels of r. proteins and higher packaging efficiency of recombinant viral particles	Bax, TRAIL, Luciferase Lentivirus	[61]
Bcl-2-associated X protein (BAX) and BCL2 Antagonist/Killer 1 (BAK)	Activation of caspase proteins	Double knockout	Resistance to apoptosis and sheer stress, 40% improvement in recombinant protein titers	Human IgG1 antibody	[60]
CrmA (viral)	Apoptosis inhibitor	Overexpression	Resistance to numerous apoptotic insults	N/A	[64]
Nuclear factor erythroid 2-related factor 2 (NRF2)	Transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins.	Overexpression	Higher growth rate, more resistant to oxidative stress. 1.7-fold improvement in r. protein expression	Recombinant coagulation factor VII	[65]