Generic placeholder image

Current Gene Therapy

Editor-in-Chief

ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

Review Article

Mammalian Stable Cell Platforms for Recombinant Adeno-associated Virus (rAAV) Production: Development Strategies and their Impact on Viral Productivity

Author(s): Sofia Fernandes, Joana Diogo and Ana Sofia Coroadinha*

Volume 23, Issue 3, 2023

Published on: 04 May, 2023

Page: [184 - 197] Pages: 14

DOI: 10.2174/1566523223666230331111336

Price: $65

conference banner
Abstract

Adeno-associated viruses (AAV) are widely used as a recombinant vectors in gene therapy. AAVs are non-pathogenic. They present reduced cytotoxicity and can transduce both dividing and non-dividing cells. The existence of different serotypes provides flexibility for targeting different tissues and organs. Its therapeutic success was already shown by the approval of three products by the European and American regulatory agencies. To satisfy the high dosage, safety, and reproducibility required in each clinical trial, production platforms based on stable mammalian cell lines have been proposed as the best strategy. However, the methodologies employed must be adapted to each cell line, which often results in distinct productivities. In this article, we review the published and commercially available mammalian stable cell lines, discussing the key factors that impact viral production yields, such as integration sites and copy numbers.

Graphical Abstract

[1]
Sun JY, Anand-Jawa V, Chatterjee S, et al. Immune responses to adeno-associated virus and its recombinant vectors. Gene Ther 2003; 10(11): 964-76.
[http://dx.doi.org/10.1038/sj.gt.3302039]
[2]
Ferreira V, Petry H, Salmon F. Immune responses to AAV-vectors, The Glybera example from bench to bedside. Front Immunol Front Res Found 2014; 5(3): 82.
[3]
Vance MA, Mitchell A, Samulski RJ. AAV Biology, Infectivity and therapeutic use from bench to clinic.In: Gene Therapy-Principles and Challenges. InTech 2015.
[4]
Mittermeyer G, Christine CW, Rosenbluth KH, et al. Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson’s disease. Hum Gene Ther 2012; 23(4): 377-81.
[http://dx.doi.org/10.1089/hum.2011.220] [PMID: 22424171]
[5]
MacLaren RE, Groppe M, Barnard AR, et al. Retinal gene therapy in patients with choroideremia: Initial findings from a phase 1/2 clinical trial. Lancet 2014; 383(9923): 1129-37.
[http://dx.doi.org/10.1016/S0140-6736(13)62117-0] [PMID: 24439297]
[6]
Rafii MS, Baumann TL, Bakay RAE, et al. A phase1 study of stereotactic gene delivery of AAV2 NGF for Alzheimer’s disease. Alzheimers Dement 2014; 10(5): 571-81.
[http://dx.doi.org/10.1016/j.jalz.2013.09.004] [PMID: 24411134]
[7]
Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, et al. Limb-girdle muscular dystrophy type 2D gene therapy restores α-sarcoglycan and associated proteins. Ann Neurol 2009; 66(3): 290-7.
[http://dx.doi.org/10.1002/ana.21732] [PMID: 19798725]
[8]
Ylä-Herttuala S. Endgame: Glybera finally recommended for approval as the first gene therapy drug in the European union. Mol Ther 2012; 20(10): 1831-2.
[9]
Simonelli F, Maguire AM, Testa F, et al. Gene therapy for Leber’s congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther 2010; 18(3): 643-50.
[http://dx.doi.org/10.1038/mt.2009.277] [PMID: 19953081]
[10]
Mendell JR, Al-Zaidy S, Shell R, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med 2017; 377(18): 1713-22.
[http://dx.doi.org/10.1056/NEJMoa1706198] [PMID: 29091557]
[11]
U.S. Food and Drug Administration. HEMGENIX. Available from: https://www.fda.gov/vaccines-blood-biologics/vaccines/hemgenix
[12]
Clément N, Grieger JC. Manufacturing of recombinant adeno-associated viral vectors for clinical trials Mol Ther - Methods Clin Dev Official journal of the American Society of Gene & Cell Therapy 2016; 3: 16002.
[http://dx.doi.org/10.1038/mtm.2016.2]
[13]
Aucoin MG, Perrier M, Kamen AA. Critical assessment of current adeno-associated viral vector production and quantification methods. Biotechnol Adv 2008; 26(1): 73-88.
[http://dx.doi.org/10.1016/j.biotechadv.2007.09.001] [PMID: 17964108]
[14]
Kohlbrenner E, Aslanidi G, Nash K, et al. Successful production of pseudotyped rAAV vectors using a modified baculovirus expression system. Mol Ther 2005; 12(6): 1217-25.
[http://dx.doi.org/10.1016/j.ymthe.2005.08.018] [PMID: 16213797]
[15]
European Medicines Agency (EMA). Assessment report: Glybera. 2012. Available from: www.ema.europa.eu
[16]
Atchison RW, Casto BC, Hammon WM. Adenovirus-associated defective virus particles Science (80-) 1965; 149(3685): 754-55.
[http://dx.doi.org/10.1126/science.149.3685.754]
[17]
Blacklow NR, Hoggan MD, Rowe WP. Isolation of adenovirus-associated viruses from man. Proc Natl Acad Sci 1967; 58(4): 1410-5.
[http://dx.doi.org/10.1073/pnas.58.4.1410] [PMID: 4295829]
[18]
Kurien BT, Scofield RH. Adeno-associated virus: methods and protocols.In: Methods in molecular biology (Clifton, NJ). New York: Humana Press 2011.
[19]
Salganik M, Hirsch ML, Samulski RJ. Adeno-associated virus as a mammalian DNA vector Microbiol Spectr 2015; 3(4): 3.4.04.
[http://dx.doi.org/10.1128/microbiolspec.MDNA3-0052-2014] [PMID: 26350320]
[20]
Samulski RJ, Berns KI, Tan M, et al. Cloning of adeno-associated virus into pBR322: Rescue of intact virus from the recombinant plasmid in human cells. Proc Natl Acad Sci USA 1982; 19(6): 2077-81.
[21]
Samulski RJ, Chang L-S. Helper-free stocks of recombinant adeno-associated viruses: Normal integration does not require viral gene expression. J Virol 1989; 63(9): 3822-8.
[22]
Samulski RJ, Muzyczka N. AAV-mediated gene therapy for research and therapeutic purposes. Annu Rev Virol 2014; 1(1): 427-51.
[http://dx.doi.org/10.1146/annurev-virology-031413-085355] [PMID: 26958729]
[23]
Penaud-Budloo M, François A, Clément N, et al. Pharmacology of recombinant adeno-associated virus production. Mol Ther Methods Clin Dev 2018; 8: 166-80.
[http://dx.doi.org/10.1016/j.omtm.2018.01.002]
[24]
Collaco RF, Cao X, Trempe JP. A helper virus-free packaging system for recombinant adeno-associated virus vectors. Gene 1999; 238(2): 397-405.
[http://dx.doi.org/10.1016/S0378-1119(99)00347-9] [PMID: 10570967]
[25]
Wright JF. Transient transfection methods for clinical adeno-associated viral vector production. Hum Gene Ther 2009; 20(7): 698-706.
[http://dx.doi.org/10.1089/hum.2009.064]
[26]
Grieger JC, Soltys SM, Samulski RJ. Production of recombinant adeno-associated virus vectors using suspension HEK293 cells and continuous harvest of vector from the culture media for GMP FIX and FLT1 clinical vector. Mol Ther 2016; 24(2): 287-97.
[http://dx.doi.org/10.1038/mt.2015.187] [PMID: 26437810]
[27]
Blessing D, Vachey G, Pythoud C, et al. Scalable production of AAV vectors in orbitally shaken HEK293 cells. Mol Ther Methods Clin Dev 2018; 13: 14.
[http://dx.doi.org/10.1016/j.omtm.2018.11.004]
[28]
Grimm D, Kleinschmidt JA. Progress in adeno-associated virus type 2 vector production: Promises and prospects for clinical use. Hum Gene Ther 1999; 10(15): 2445-50.
[http://dx.doi.org/10.1089/10430349950016799] [PMID: 10543610]
[29]
Loo JCM. van der, Wright JF. Progress and challenges in viral vector manufacturing. Hum Mol Genet 2016; 25(R1): R42-52.
[30]
Moleirinho MG, Silva RJS, Alves PM, et al. Current challenges in biotherapeutic particles manufacturing. Expert Opin Biol Ther 2020; 20(5): 451-65.
[31]
Chen H. Intron splicing-mediated expression of AAV Rep and Cap genes and production of AAV vectors in insect cells. Mol Ther 2008; 16(5): 924-30.
[http://dx.doi.org/10.1038/mt.2008.35] [PMID: 18388928]
[32]
Urabe M, Ding C, Kotin RM. Insect cells as a factory to produce adeno-associated virus type 2 vectors. Hum Gene Ther 2002; 13(16): 1935-43.
[http://dx.doi.org/10.1089/10430340260355347] [PMID: 12427305]
[33]
Smith RH, Levy JR, Kotin RM. A simplified baculovirus-AAV expression vector system coupled with one-step affinity purification yields high-titer rAAV stocks from insect cells. Mol Ther 2009; 17(11): 1888-96.
[http://dx.doi.org/10.1038/mt.2009.128] [PMID: 19532142]
[34]
Wu Y, Mei T, Jiang L, et al. Development of versatile and flexible sf9 packaging cell line-dependent onebac system for large-scale recombinant adeno-associated virus production. Hum Gene Ther Methods 2019; 30(5): 172-83.
[http://dx.doi.org/10.1089/hgtb.2019.123] [PMID: 31566024]
[35]
Conway JE, Rhys CMJ, Zolotukhin I, et al. High-titer recombinant adeno-associated virus production utilizing a recombinant herpes simplex virus type I vector expressing AAV-2 Rep and Cap. Gene Ther 1999; 6(6): 986-93.
[http://dx.doi.org/10.1038/sj.gt.3300937] [PMID: 10455400]
[36]
Thomas DL, Wang L, Niamke J, et al. Scalable recombinant adeno-associated virus production using recombinant herpes simplex virus type 1 coinfection of suspension-adapted mammalian cells. Hum Gene Ther 2009; 20(8): 861-70.
[http://dx.doi.org/10.1089/hum.2009.004] [PMID: 19419276]
[37]
Adamson-Small L, Potter M, Falk DJ, et al. A scalable method for the production of high-titer and high-quality adeno-associated type 9 vectors using the HSV platform. Mol Ther Methods Clin Dev 2016; 3: 16031.
[http://dx.doi.org/10.1038/mtm.2016.31]
[38]
Ye G, Scotti MM, Thomas DL, Wang L, Knop DR, Chulay JD. Herpes simplex virus clearance during purification of a recombinant adeno-associated virus serotype 1 vector. Hum Gene Ther Clin Dev 2014; 25(4): 212-7.
[http://dx.doi.org/10.1089/humc.2014.060] [PMID: 25357151]
[39]
Yuan Z, Qiao C, Hu P, Li J, Xiao X. A versatile adeno-associated virus vector producer cell line method for scalable vector production of different serotypes. Hum Gene Ther 2011; 22(5): 613-24.
[http://dx.doi.org/10.1089/hum.2010.241] [PMID: 21186998]
[40]
Qiao C, Wang B, Zhu X, Li J, Xiao X. A novel gene expression control system and its use in stable, high-titer 293 cell-based adeno-associated virus packaging cell lines. J Virol 2002; 76(24): 13015-27.
[http://dx.doi.org/10.1128/JVI.76.24.13015-13027.2002] [PMID: 12438627]
[41]
Clark KR, Voulgaropoulou F, Fraley DM, Johnson PR. Cell lines for the production of recombinant adeno-associated virus. Hum Gene Ther 1995; 6(10): 1329-41.
[http://dx.doi.org/10.1089/hum.1995.6.10-1329] [PMID: 8590738]
[42]
Inoue N, Russell DW. Packaging cells based on inducible gene amplification for the production of adeno-associated virus vectors. J Virol 1998; 72(9): 7024-31.
[http://dx.doi.org/10.1128/JVI.72.9.7024-7031.1998] [PMID: 9696794]
[43]
Gao GP, Qu G, Faust LZ, et al. High-titer adeno-associated viral vectors from a Rep/Cap cell line and hybrid shuttle virus. Hum Gene Ther 1998; 9(16): 2353-62.
[http://dx.doi.org/10.1089/hum.1998.9.16-2353] [PMID: 9829534]
[44]
Gao GP, Lu F, Sanmiguel JC, et al. Rep/cap gene amplification and high-yield production of AAV in an A549 cell line expressing rep/cap. Mol Ther 2002; 5(5 I): 644-49.
[45]
Chadeuf G, Favre D, Tessier J, et al. Efficient recombinant adeno-associated virus production by a stable rep-cap HeLa cell line correlates with adenovirus-induced amplification of the integrated rep-cap genome. J Gene Med 2000; 2(4): 260-8.
[http://dx.doi.org/10.1002/1521-2254(200007/08)2:4<260:AID-JGM111>3.0.CO;2-8] [PMID: 10953917]
[46]
Qiao C, Li J, Skold A, Zhang X, Xiao X. Feasibility of generating adeno-associated virus packaging cell lines containing inducible adenovirus helper genes. J Virol 2002; 76(4): 1904-13.
[http://dx.doi.org/10.1128/JVI.76.4.1904-1913.2002] [PMID: 11799185]
[47]
Toublanc E, Benraiss A, Bonnin D, et al. Identification of a replication-defective herpes simplex virus for recombinant adeno-associated virus type 2(rAAV2) particle assembly using stable producer cell lines. J Gene Med 2004; 6(5): 555-64.
[http://dx.doi.org/10.1002/jgm.542] [PMID: 15133766]
[48]
Flotte T, Carter B, Conrad C, et al. A phase I study of an adeno-associated Virus-CFTR gene vector in adult CF patients with mild lung disease. Hum Gene Ther 1996; 7(9): 1145-59.
[49]
Thorne BA, Takeya RK, Peluso RW. Manufacturing recombinant adeno-associated viral vectors from producer cell clones. Hum Gene Ther 2009; 20(7): 707-14.
[http://dx.doi.org/10.1089/hum.2009.070]
[50]
Martin J, Frederick A, Luo Y, et al. Generation and characterization of adeno-associated virus producer cell lines for research and preclinical vector production. Hum Gene Ther Methods 2013; 24(4): 253-69.
[http://dx.doi.org/10.1089/hgtb.2013.046] [PMID: 23848282]
[51]
Luo Y, Frederick A, Martin JM, et al. AAVS1-targeted plasmid integration in AAV producer cell lines. Hum Gene Ther Methods 2017; 28(3): 124-38.
[http://dx.doi.org/10.1089/hgtb.2016.158] [PMID: 28504553]
[52]
Hebben M. Downstream bioprocessing of AAV vectors: Industrial challenges & regulatory requirements. Cell Gene Ther Insights BioInsights 2018; 4(2): 131-46.
[53]
Farson D, Harding TC, Tao L, et al. Development and characterization of a cell line for large-scale, serum-free production of recombinant adeno-associated viral vectors. J Gene Med 2004; 6(12): 1369-81.
[http://dx.doi.org/10.1002/jgm.622] [PMID: 15538729]
[54]
Office of Technology Transfer N. A549 Cells. Lung Carcinoma Cell Line for Adenovirus 2018. Available from: https://www.ott.nih.gov/technology/e-129-2009
[55]
Berthet C, Raj K, Saudan P, Beard P. How adeno-associated virus Rep78 protein arrests cells completely in S phase. Proc Natl Acad Sci USA 2005; 102(38): 13634-9.
[http://dx.doi.org/10.1073/pnas.0504583102] [PMID: 16157891]
[56]
Li Z, Brister JR, Im DS, Muzyczka N. Characterization of the adenoassociated virus Rep protein complex formed on the viral origin of DNA replication. Virology 2003; 313(2): 364-76.
[http://dx.doi.org/10.1016/S0042-6822(03)00340-4] [PMID: 12954205]
[57]
Yang Q, Chen F, Trempe JP. Characterization of cell lines that inducibly express the adeno-associated virus Rep proteins. J Virol 1994; 68(8): 4847-56.
[http://dx.doi.org/10.1128/jvi.68.8.4847-4856.1994] [PMID: 8035483]
[58]
Schmidt M, Afione S, Kotin RM. Adeno-associated virus type 2 Rep78 induces apoptosis through caspase activation independently of p53. J Virol 2000; 74(20): 9441-50.
[http://dx.doi.org/10.1128/JVI.74.20.9441-9450.2000] [PMID: 11000213]
[59]
Saudan P, Vlach J, Beard P. Inhibition of S-phase progression by adeno-associated virus Rep78 protein is mediated by hypophosphorylated pRb. EMBO J 2000; 19(16): 4351-61.
[http://dx.doi.org/10.1093/emboj/19.16.4351] [PMID: 10944118]
[60]
Ogasawara Y, Mizukami H, Urabe M, et al. Highly regulated expression of adeno-associated virus large Rep proteins in stable 293 cell lines using the Cre/loxP switching system. J Gen Virol 1999; 80(9): 2477-80.
[http://dx.doi.org/10.1099/0022-1317-80-9-2477] [PMID: 10501504]
[61]
Pereira DJ, McCarty DM, Muzyczka N. The adeno-associated virus (AAV) Rep protein acts as both a repressor and an activator to regulate AAV transcription during a productive infection. J Virol 1997; 71(2): 1079-88.
[http://dx.doi.org/10.1128/jvi.71.2.1079-1088.1997] [PMID: 8995628]
[62]
Okada T, Mizukami H, Urabe M, et al. Development and characterization of an antisense-mediated prepackaging cell line for adeno-associated virus vector production. Biochem Biophys Res Commun 2001; 288(1): 62-8.
[http://dx.doi.org/10.1006/bbrc.2001.5730] [PMID: 11594752]
[63]
Mizukami H, Okada T, Ogasawara Y, et al. Separate control of Rep and Cap expression using mutant and wild-type loxP sequences and improved packaging system for adeno-associated virus vector production Mol Biotechnol 2004; 27(1): 07-14.
[http://dx.doi.org/10.1385/MB:27:1:07] [PMID: 15122043]
[64]
Pharmaceuticals CEVEC. CEVEC closes growth financing round to serve strong demand in viral vector technologies for cell and gene therapies 2021. Available from: https://cevec.com/news/press-releases/cevec-closes-growth-financing/
[65]
CEVEC. CEVEC introduces CAP®GT-CEVEC 2015. Available from: https://cevec.com/news/press-releases/cevec-introduces-capgt/
[66]
Schiedner G, Hertel S, Bialek C, et al. Efficient and reproducible generation of high-expressing, stable human cell lines without need for antibiotic selection. BMC Biotechnol 2008; 8(1): 1-11.
[http://dx.doi.org/10.1186/1472-6750-8-13]
[67]
Swiech K, Picanço-Castro V, Covas DT. Human cells: New platform for recombinant therapeutic protein production. Protein Expr Purif 2012; 84(1): 147-53.
[http://dx.doi.org/10.1016/j.pep.2012.04.023] [PMID: 22580292]
[68]
CEVEC Biopharmaceuticals. Stable AAV Production. Available from: https://cevec.com/applications/aav/
[69]
CEVEC Pharmaceuticals GmbH CAP ® GT Stable AAV Production 2019.
[70]
Hein K, Faust N, Wissing S. inducible AAV rep genes. Patent WO2019057691A1, 2019.
[71]
Wissing S. ELEVECTA - Helper virus-free AAV production with stable CAP and HEK293 producer cells. 2019.Available from: https://cevec.com/technologies/elevecta-platform/
[72]
Liu X, Voulgaropoulou F, Chen R, Johnson PR, Clark KR. Selective Rep-Cap gene amplification as a mechanism for high-titer recombinant AAV production from stable cell lines. Mol Ther 2000; 2(4): 394-403.
[http://dx.doi.org/10.1006/mthe.2000.0132] [PMID: 11020356]
[73]
Berns KI, Pinkerton TC, Thomas GF, Hoggan MD. Detection of adeno-associated virus (AAV)-specific nucleotide sequences in DNA isolated from latently infected Detroit 6 cells. Virology 1975; 68(2): 556-60.
[http://dx.doi.org/10.1016/0042-6822(75)90298-6] [PMID: 1198930]
[74]
Cheung AK, Hoggan MD, Hauswirth WW, Berns KI. Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells. J Virol 1980; 33(2): 739-48.
[http://dx.doi.org/10.1128/jvi.33.2.739-748.1980] [PMID: 6251245]
[75]
Wonderling RS, Owens RA. Binding sites for adeno-associated virus Rep proteins within the human genome. J Virol 1997; 71(3): 2528-34.
[http://dx.doi.org/10.1128/jvi.71.3.2528-2534.1997] [PMID: 9032395]
[76]
Hüser D, Gogol-Döring A, Lutter T, et al. Integration preferences of wildtype AAV-2 for consensus rep-binding sites at numerous loci in the human genome. PLoS Pathog 2010; 6(7)e1000985
[http://dx.doi.org/10.1371/journal.ppat.1000985] [PMID: 20628575]
[77]
Feng D, Chen J, Yue Y, Zhu H, Xue J, Jia WWA. 16bp Rep binding element is sufficient for mediating Rep-dependent integration into AAVS1. J Mol Biol 2006; 358(1): 38-45.
[http://dx.doi.org/10.1016/j.jmb.2006.01.029] [PMID: 16516232]
[78]
Philpott NJ, Gomos J, Berns KI, Falck-Pedersen EA. p5 integration efficiency element mediates Rep-dependent integration into AAVS1 at chromosome 19. Proc Natl Acad Sci 2002; 99(19): 12381-5.
[http://dx.doi.org/10.1073/pnas.182430299] [PMID: 12221283]
[79]
Cao L, During M, Xiao W. Replication competent helper functions for recombinant AAV vector generation. Gene Ther 2002; 9(18): 1199-206.
[http://dx.doi.org/10.1038/sj.gt.3301710] [PMID: 12215886]
[80]
Weger S, Wistuba A, Grimm D, et al. Control of adeno-associated virus Type 2 cap gene expression: Relative influence of helper virus, terminal repeats, and rep proteins. J Virol 1997; 71(11): 8437-47.
[81]
Ward P, Elias P, Linden RM. Rescue of the adeno-associated virus genome from a plasmid vector: Evidence for rescue by replication. J Virol 2003; 77(21): 11480-90.
[http://dx.doi.org/10.1128/JVI.77.21.11480-11490.2003] [PMID: 14557633]
[82]
Nony P, Tessier J, Chadeuf G, et al. Novel cis-acting replication element in the adeno-associated virus type 2 genome is involved in amplification of integrated rep-cap sequences. J Virol 2001; 75(20): 9991-4.
[http://dx.doi.org/10.1128/JVI.75.20.9991-9994.2001] [PMID: 11559833]
[83]
Tessier J, Chadeuf G, Nony P, Avet-Loiseau H, Moullier P, Salvetti A. Characterization of adenovirus-induced inverted terminal repeat-independent amplification of integrated adeno-associated virus rep-cap sequences. J Virol 2001; 75(1): 375-83.
[http://dx.doi.org/10.1128/JVI.75.1.375-383.2001] [PMID: 11119606]
[84]
Fan PD, Dong JY. Replication of rep-cap genes is essential for the high-efficiency production of recombinant AAV. Hum Gene Ther 1997; 8(1): 87-98.
[http://dx.doi.org/10.1089/hum.1997.8.1-87] [PMID: 8989998]
[85]
Tratschin J-D, Miller IL, Smith MG, Carter BJ. Adeno-associated virus vector for high-frequency integration, expression, and rescue of genes in mammalian cells. Mol Cell Biol 1985; 5(11): 3251-60.
[PMID: 3018511]
[86]
Mathews LC, Gray JT, Gallagher MR, Snyder RO. Recombinant adeno-associated viral vector production using stable packaging and producer cell lines. Methods Enzymol 2002; 346: 393-413.
[http://dx.doi.org/10.1016/S0076-6879(02)46068-5] [PMID: 11883082]
[87]
Blouin V, Brument N, Toublanc E, Raimbaud I, Moullier P, Salvetti A. Improving rAAV production and purification: Towards the definition of a scaleable process. J Gene Med 2004; 6(S1): S223-8.
[http://dx.doi.org/10.1002/jgm.505] [PMID: 14978765]
[88]
Walz C, Deprez A, Dupressoir T, Dürst M, Rabreau M, Schlehofer JR. Interaction of human papillomavirus type 16 and adeno-associated virus type 2 co-infecting human cervical epithelium. J Gen Virol 1997; 78(Pt 6): 1441-52.
[http://dx.doi.org/10.1099/0022-1317-78-6-1441] [PMID: 9191942]
[89]
Graham FL, Russell WC, Smiley J, Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 1977; 36(1): 59-72.
[http://dx.doi.org/10.1099/0022-1317-36-1-59] [PMID: 886304]
[90]
Louis N, Evelegh C, Graham FL. Cloning and sequencing of the cellular-viral junctions from the human adenovirus type 5 transformed 293 cell line. Virology 1997; 233(2): 423-9.
[http://dx.doi.org/10.1006/viro.1997.8597] [PMID: 9217065]
[91]
Dumont J, Euwart D, Mei B, Estes S, Kshirsagar R. Human cell lines for biopharmaceutical manufacturing: History, status, and future perspectives. Crit Rev Biotechnol 2016; 36(6): 1110-22.
[http://dx.doi.org/10.3109/07388551.2015.1084266] [PMID: 26383226]
[92]
Clark KR, Voulgaropoulou F, Johnson PR. A stable cell line carrying adenovirus-inducible rep and cap genes allows for infectivity titration of adeno-associated virus vectors. Gene Ther 1996; 3(12): 1124-32.
[PMID: 8986439]
[93]
Clark KR, Liu X, Mcgrath JP, Johnson PR. Highly purified recombinant adeno-associated virus vectors are biologically active and free of detectable helper and wild-type viruses. Hum Gene Ther 1999; 10(6): 1031-9.
[http://dx.doi.org/10.1089/10430349950018427] [PMID: 10223736]
[94]
Tamayose K, Hirai Y, Shimada T. A new strategy for large-scale preparation of high-titer recombinant adeno-associated virus vectors by using packaging cell lines and sulfonated cellulose column chromatography. Hum Gene Ther 1996; 7(4): 507-13.
[http://dx.doi.org/10.1089/hum.1996.7.4-507] [PMID: 8800745]
[95]
Jenny C, Toublanc E, Danos O, Merten OW. Evaluation of a serum-free medium for the production of rAAV-2 using HeLa derived producer cells. Cytotechnology 2005; 49(1): 11-23.
[http://dx.doi.org/10.1007/s10616-005-5361-z] [PMID: 19003059]
[96]
Nakamura S, Nakamura R, Shibata K, et al. Development of packaging cell lines for generation of adeno-associated virus vectors by lentiviral gene transfer of trans-complementary components. Eur J Haematol 2004; 73(4): 285-94.
[http://dx.doi.org/10.1111/j.1600-0609.2004.00290.x] [PMID: 15347316]
[97]
Hudjetz B. AAV manufacturing with stable producer cells for industrial scale vector production. Available from: https://www.insights.bio/cell-and-gene-therapyinsights/webinars/256/AAV-manufacturing-with-stable-producercells-for-industrial-scale-vector-production

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy