Table 6.

Genes that have been engineered to improve recombinant protein folding in the HEK293 cell line.

Gene	Function	Modification	Outcome	Recombinant Protein	Reference
Human resistance to inhibitors of cholinesterase 3 (RIC3)	Molecular chaperone of nicotinic acetylcholine receptors	Overexpression	Expression of high levels of functional receptor protein	α7 nicotinic acetyl cholinesterase receptor	[95]
X-box binding protein (XBP1)	Induces the unfolded protein response by upregulating target genes encoding ER chaperones and ER-associated degradation (ERAD) components to enhance the capacity of productive folding and degradation mechanism, respectively.	Overexpression	Improvement in volumetric and cell specific gamma retroviral productivity	Gamma retroviral vectors	[66]
Protein Disulfide Isomerase Family A Member 2 (PDIA2)	Folding of nascent proteins in the endoplasmic reticulum by forming disulfide bonds through its thiol isomerase, oxidase and reductase activity
Heat shock protein family A (Hsp70) member 5 (HSPA5)	Plays a key role in protein folding and quality control in the endoplasmic reticulum lumen. Involved in the correct folding of proteins and degradation of misfolded proteins.
Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1)	Carboxylation of glutamic acid residues in some blood-clotting proteins, including factor VII, factor IX, and factor X	Overexpression	Improved γ-carboxylation	rhFVII	[97]
Calumenin (CALU)	Inhibitor of γ-carboxylase	shRNA inhibition	Up to 7.5-fold increase in production yield of active enzyme	rhFX	[96]