CHO细胞工程化改造的研究进展
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摘要
该文综述了CHO细胞工程化改造相关研究的最新进展,对CHO细胞在调节代谢、抗凋亡和糖基化等方面的工程改造及应用进行了归纳和总结,提出了CHO表达系统应用中可能出现的问题,并对CHO细胞表达系统应用前景进行了展望,以期为后续相关研究提供思路。
In this paper,the latest research progress of summarizes the CHO cells engineering progress was reviewed,we mainly discussed and summarized the CHO cells in regulating metabolism,antiapoptotic and glycosylation engineering and application,proposed the CHO expression system applications,the potential problems and prospect of CHO cell expression system application was discussed,which was expected to provides ideas for subsequent research.
In this paper,the latest research progress of summarizes the CHO cells engineering progress was reviewed,we mainly discussed and summarized the CHO cells in regulating metabolism,antiapoptotic and glycosylation engineering and application,proposed the CHO expression system applications,the potential problems and prospect of CHO cell expression system application was discussed,which was expected to provides ideas for subsequent research.
引文
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[3]Kuo C C,Chiang A W,Shamie I,et al.The emerging role of systems biology for engineering protein production in CHO cells[J].Curr Opin Biotechnol,2018,51:64-69.
[4]王登,刘煜.用于重组蛋白表达的哺乳动物细胞系的研究进展[J].药物生物技术,2014,21(05):478-482.
[5]Shan Q,Baltes N J,Atkins P,et al.ZFN,TALEN and CRISPR-Cas9 mediated homology directed gene insertion in Arabidopsis:a disconnect between somatic and germinal cells[J].J Genet Genomics,2018,45(12):681-684.
[6]Hirano S,Nishimasu H,Ishitani R,et al.Structural basis for the altered PAM specificities of engineered CRISPR-Cas9[J].Mol Cell,2016,61(6):886-894.
[7]刘娜,袁宝珠.利用细胞工程技术改造蛋白生产用CHO细胞的研究进展[J].中国医药生物技术,2014,9(5):369-371.
[8]Fischer S,Handrick R,Otte K.The art of CHO cell engineering:Acomprehensive retrospect and future perspectives[J].Biotechnol Adv,2015,33(8):1878-1896.
[9]Coleman O,Suda S,Meiller J,et al.Increased growth rate and productivity following stable depletion of miR-7 in a m Ab producing CHO cell line causes an increase in proteins associated with the Akt pathway and ribosome biogenesis[J].J Proteomics,2019,195:23-32.
[10]Kim J Y,Kim Y G,Lee G M.CHO cells in biotechnology for production of recombinant proteins:current state and further potential[J].Appl Microbiol Biotechnol,2012,93(3):17-30.
[11]郑惠惠,江洪.CHO细胞表达系统研究进展[J].生物技术进展,2016,6(4):239-243.
[12]惠开元,高向东,徐晨.单克隆抗体制备的细胞工程学研究进展[J].中国生物工程杂志,2012,32(2):90-95.
[13]Arden N.,Betenbaugh M.J.Life and death in mammalian cell culture:strategies for apoptosis inhibition[J].Trends Biotechnol,2004,22(4):74-80.
[14]Zhang X.,Han L.,Zong H.,et al.Enhanced production of antiPD1 antibody in CHO cells through transient co-transfection with anti-apoptotic genes Bcl-x L and Mcl-1[J].Bioprocess Biosyst Eng,2018,41(5):633-640.
[15]张存超,寇庚,王皓.基因工程改造与中国仓鼠卵巢细胞凋亡[J].化学与生物工程,2014,31(12):1-3.
[16]Baek E,Noh S M,Lee G M.Anti-Apoptosis engineering for improved protein production from CHO cells[J].Methods Mol Biol,2017,16(03):71-85.
[17]Han S,Rhee W J.Inhibition of apoptosis using exosomes in Chinese hamster ovary cell culture[J].Biotechnol Bioeng,2018,115(5):1331-1339.
[18]Chiang G G,Sisk W P.Bcl-x(L)mediates increased production of humanized monoclonal antibodies in Chinese hamster ovary cells[J].Biotechnol Bioeng,2005,91(7):779-792.
[19]Kim N S,Lee G M.Overexpression of bcl-2 inhibits sodium butyrate-induced apoptosis in Chinese hamster ovary cells resulting in enhanced humanized antibody production[J].Biotechnol Bioeng,2000,71(3):184-193.
[20]Cost G J,Freyvert Y,Vafiadis A,et al.BAK and BAX deletion using zinc-finger nucleases yields apoptosis-resistant CHO cells[J].Biotechnol Bioeng,2010,105(2):330-340.
[21]Majors B S,Betenbaugh M J,Pederson N E,et al.Mcl-1 overexpression leads to higher viabilities and increased production of humanized monoclonal antibody in Chinese hamster ovary cells[J].Biotechnol Prog,2009,25(4):1161-1168.
[22]Meents H,Enenkel B,Eppenberger H M,et al.Impact of coexpression and coamplification of s ICAM and antiapoptosis determinants bcl-2/bcl-x(L)on productivity,cell survival,and mitochondria number in CHO-DG44 grown in suspension and serum-free media[J].Biotechnol Bioeng,2002,80(6):706-716.
[23]Tey B T,Singh R P,Piredda L,et al.Influence of bcl-2 on cell death during the cultivation of a Chinese hamster ovary cell line expressing a chimeric antibody[J].Biotechnol Bioeng,2000,68(1):31-43.
[24]Sung Y H,Lee J S,Park S H,et al.Influence of co-down-regulation of caspase-3 and caspase-7 by siRNAs on sodium butyrate-induced apoptotic cell death of Chinese hamster ovary cells producing thrombopoietin[J].Metab Eng,2007,9(5-6):452-464.
[25]Kim N S,Lee GM.Inhibition of sodium butyrate-induced apoptosis in recombinant Chinese hamster ovary cells by constitutively expressing antisense RNA of caspase-3[J].Biotechnol Bioeng,2002,78(2):217-228.
[26]Yun C Y,Liu S,Lim S F,et al.Specific inhibition of caspase-8and-9 in CHO cells enhances cell viability in batch and fedbatch cultures[J].Metab Eng,2007,9(5-6):406-418.
[27]Sauerwald T M,Oyler G A,Betenbaugh M J.Study of caspase inhibitors for limiting death in mammalian cell culture[J].Biotechnol Bioeng,2003,81(3):329-340.
[28]Figueroa B,Jr.Ailor,E Osborne,et al.Enhanced cell culture performance using inducible anti-apoptotic genes E1B-19K and Aven in the production of a monoclonal antibody with Chinese hamster ovary cells[J].Biotechnol Bioeng,2007,97(4):877-892.
[29]Arden N,Majors B S,Ahn S H,et al.Inhibiting the apoptosis pathway using MDM2 in mammalian cell cultures[J].Biotechnol Bioeng,2007,97(3):601-614.
[30]Crea F,Sarti D,Falciani F,et al.Over-expression of hTERT in CHO K1 results in decreased apoptosis and reduced serum dependency[J].J Biotechnol,2006,121(2):109-123.
[31]Tabuchi H,Sugiyama T,Tanaka S,et al.Overexpression of taurine transporter in Chinese hamster ovary cells can enhance cell viability and product yield,while promoting glutamine consumption[J].Biotechnol Bioeng,2010,107(6):998-1003.
[32]Jeon M K,Yu D Y,Lee G M.Combinatorial engineering of ldh-a and bcl-2 for reducing lactate production and improving cell growth in dihydrofolate reductase-deficient Chinese hamster ovary cells[J].Appl Microbiol Biotechnol,2011,92(4):779-790.
[33]Kim Y G,Lee GM.Bcl-x L overexpression does not enhance specific erythropoietin productivity of recombinant CHO cells grown at33 degrees C and 37 degrees C[J].Biotechnol Prog,2009,25(1):252-256.
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