Modified mammalian cells for improved production

Abstract

This article provides engineered or modified cell lines in which at least one of the following cell lines exhibits altered expression or activity compared to control cell lines: ADM2, AURKA, BCL2, CCND1, CHD1, CREB3L3, RIGI / DDX58, ECSIT, EHHADH, ERBB2, FAS, FBXW7, FGFR3, FOXL2, GATA1, HDAC5, HOXA5, HSP90B1, IL6, ITGA2B, KAT5, LAS1L, LIF, NFKB1, NFKB2, NFKB1A, NFE2L2, NGEF, NME1, NR3C1, POLN, PPAR- A. PTEN, RELB, RPA1, RXRA, SMAD4, SS18, TCF7, TGM2, THEM6, TNFAIP3, TP63, TRPC1, DBH, ITGAM, HHEX, TXNIP, ASNS, PLEKH02, CDKN1A, C5orf64, C OL20A1, GJB3, ISYNA1, PARD6G-AS1, ACTA1, ACTC1, ADCY10, ADCY4, ADORA2A, ALKBH5, ATP1A4, ATP1B2, ATP2B2, BAIAP3, BAZ1B, BTK, CBL, CCNA1, C D14, CLTC, COPS3, CRHR2, CXADR, DAPK1, DCTN5, DYNLRB1, EME2, EXOC3L1, EYA3, EYA4, FANCA, FEN1, GAK, GCGR, GHSR, GSK3B, H2BC5, H4C7, H4C8, H AP1, HCAR1, INO80, KCNB1, LAT2, LIN7C, MAP1B, MBD4, MYH11, MYH15, MYH3, MYH7B, NAPA, NKD2, NLRP5, NPM2, NR4A3, NFRKB, PAXIP1, PIAS1, PIAS4, POLE, POLE3, POLD1, POLH, PPP4R2, PTGER3, RAB25, RAB40C, RAB44, RAD9A, REV1, RIF1, RNF111, RNF168, RNF4, RPA4, RTEL1, SCRIB, SNRNP70, SPHK1, STX3, SYT1, SYT2, SYT5, SYTL1, SYNJ2, TERF2, TNFSF10, TNPO2, TOP3A, TRIM25, TRIM72, TXLNA, UBA7, UNC5A, VAV3, VPS18, WASL, XRN2, and YY1. A method for producing recombinant AAV particles in the engineered or modified cell lines is also provided. Provided herein are engineered or modified cell lines in which the expression of at least one of ADM2, AURKA, BCL2, CCND1, CHD1, CREB3L3, RIGI / DDX58, ECSIT, EHHADH, ERBB2, FAS, FBXW7, FGFR3, FOXL2, GATA1, HDAC5, HOXA5, HSP90B1, IL6, ITGA2B, KAT5, LAS1L, LIF, NFKB1, NFKB2, NFKB1A, NFE2L2, NGEF, NME1, NR3C1, POLN, PPAR-A, PTEN, RELB, RPA1, RXRA, SMAD4, SS18, TCF7, TGM2, THEM6, TNFAIP3, TP63, TRPC1, DBH, ITGAM, HHEX, TXNIP, ASNS, PLEKH02, CDKN1A, C5orf64, COL20A1, GJB3, ISYNA1, PARD6G-AS1, ACTA1, ACTC1, ADCY10, ADCY4, ADORA2A, ALKBH5, ATP1A4, ATP1B2, ATP2B2, BAIAP3, BAZ1B, BTK, CBL, CCNA1, CD14, CLTC, COPS3, CRHR2, CXADR, DAPK1, DCTN5, DYNLRB1, EME2, EXOC3L1, EYA3, EYA4, FANCA, FEN1, GAK, GCGR, GHSR, GSK3B, H2BC5, H4C7, H4C8, HAP1, HCAR1, INO80, KCNB1, LAT2, LIN7C, MAP1B, MBD4, MYH11, MYH15, MYH3, MYH7B, NAPA, NKD2, NLRP5, NPM2, NR4A3, NFRKB, PAXIP1, PIAS1, PIAS4, POLE, POLE3, POLD1, POLH, PPP4R2, PTGER3, RAB25, RAB40C, RAB44, RAD9A, REV1, RIF1, RNF111, RNF168, RNF4, RPA4, RTEL1, SCRIB,SNRNP70, SPHK1, STX3, SYT1, SYT2, SYT5, SYTL1, SYNJ2, TERF2, TNFSF10, TNPO2, TOP3A, TRIM25, TRIM72, TXLNA, UBA7, UNC5A, VAV3, VPS18, WASL, XRN2, and YY1 is altered as compared to a control cell line. Also provided are methods of producing recombinant AAV particles in said engineered or modified cell lines.,

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