RNAi suppression of Bax and Bak enhances viability in fed-batch cultures of CHO cells

BAK and BAX deletion using zinc‐finger nucleases yields apoptosis‐resistant CHO cells

“…In addition, Bcl-2 over-expression in human cells down-regulates the non-homologous end-joining (NHEJ) and mismatch DNA repair pathways, resulting in abnormal metaphase chromosomes in 30% of cell divisions (Hou et al, 2007;Wang et al, 2008). An alternate approach was taken by Lim et al (2006), who reduced expression of BAX and BAK using RNA interference. CHO cells with these knockdowns of Bax and Bak are resistant to the apoptotic stresses present during protein production (Lim et al, 2006).…”

Autophagy and apoptosis in Chinese hamster ovary cell culture

“…Up to now, there have been many approaches to overcome apoptotic cell death during batch cultures by (1) genetically modifying important genes in cell growth, 8,[10][11][12][13][14][15][16][17][18] (2) supplementing essential nutrients, [19][20][21] or (3) adding chemical inhibitors. 22,23 We address each of these approaches below.…”

“…14,15 Also, reports on downregulation of caspases have shown to inhibit the execution of apoptosis. 16,17 In addition, Lim et al 18 show that pro-apoptotic Bcl-2 family proteins such as Bax and BAK when down-regulated by siRNA result in the increase of viability during fed-batch culture.…”

Du milligramme à la tonne d’anticorps monoclonaux

“…Des modifications cellulaires ont été également décrites pour prolonger la durée de culture des cellules en bioréacteur. Une des stratégies se base par exemple sur l'utilisation d'ARN interférents pour inhiber des gènes proapoptotiques tels que Bax, Bak ou caspase 3 [15,16]. À l'inverse, des copies additionnelles de gènes anti-apoptotiques tels que Bcl-2 et Bcl-X L ont été insérées dans la cellule productrice, augmentant sa survie, et donc entraînant l'augmentation des rendements de production [17].…”