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Cited by 55Virus-based gene therapy researchRNA Interference and Gene DeliveryViral Infectious Diseases and Gene Expression in Insects

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Replication-competent Lentivirus Analysis of Clinical Grade Vector Products

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Cornetta, Kenneth, Yao, Jing, Jasti, Aparna, Koop, Sue, Douglas, Makhaila, Hsu, David, Couture, Larry A, Hawkins, Troy, Duffy, Lisa·2011·Molecular Therapy
DOI 10.1038/mt.2010.278PMC PMC3048188
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Abstract

Lentiviral vectors are now in clinical trials for a variety of inherited and acquired disorders. A challenge for moving any viral vector into the clinic is the ability to screen the vector product for the presence of replication-competent virus. Assay development for replication-competent lentivirus (RCL) is particularly challenging because recombination of vector packaging plasmids and cellular DNA leading to RCL has not been reported with the current viral vector systems. Therefore, the genomic structure of a RCL remains theoretical. In this report, we describe a highly sensitive RCL assay suitable for screening vector product and have screened large-scale vector supernatant, cells used in vector production, and cells transduced with clinical grade vector. We discuss the limitations and challenges of the current assay, and suggest modifications that may improve the suitability of this assay for screening US Food and Drug Administration (US FDA)-licensed products.

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Research works printed but not linked: 50

  1. Segall, 2003, Characterization and detection of artificial replication-competent lentivirus of altered host range, Mol Ther, 8, 118, 10.1016/S1525-0016(03)00134-5 · DOI
  2. Delenda, 2002, Biosafety issues in lentivector production, Curr Top Microbiol Immunol, 261, 123
  3. Mautino, 2000, Modified human immunodeficiency virus-based lentiviral vectors display decreased sensitivity to trans-dominant Rev, Hum Gene Ther, 11, 895, 10.1089/10430340050015509 · DOI
  4. Srinivasakumar, 1999, A lentivirus packaging system based on alternative RNA transport mechanisms to express helper and gene transfer vector RNAs and its use to study the requirement of accessory proteins for particle formation and gene delivery, J Virol, 73, 9589, 10.1128/JVI.73.11.9589-9598.1999 · DOI
  5. Evans, 2000, Lentivirus vector mobilization and spread by human immunodeficiency virus, Hum Gene Ther, 11, 2331, 10.1089/104303400750038444 · DOI
  6. Wu, 2000, Development of a novel trans-lentiviral vector that affords predictable safety, Mol Ther, 2, 47, 10.1006/mthe.2000.0095 · DOI · Paper page
  7. Cronin, 2005, Altering the tropism of lentiviral vectors through pseudotyping, Curr Gene Ther, 5, 387, 10.2174/1566523054546224 · DOI
  8. Dull, 1998, A third-generation lentivirus vector with a conditional packaging system, J Virol, 72, 8463, 10.1128/JVI.72.11.8463-8471.1998 · DOI · Paper page
  9. Zufferey, 1998, Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery, J Virol, 72, 9873, 10.1128/JVI.72.12.9873-9880.1998 · DOI · Paper page
  10. Urnovitz, 1996, Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease, Clin Microbiol Rev, 9, 72, 10.1128/CMR.9.1.72 · DOI
  11. Naldini, 1996, In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector, Science, 272, 263, 10.1126/science.272.5259.263 · DOI · Paper page
  12. Sastry, 2002, Titering lentiviral vectors: comparison of DNA, RNA and marker expression methods, Gene Ther, 9, 1155, 10.1038/sj.gt.3301731 · DOI
  13. Metharom, 2000, Novel bovine lentiviral vectors based on Jembrana disease virus, J Gene Med, 2, 176, 10.1002/(SICI)1521-2254(200005/06)2:3<176::AID-JGM106>3.0.CO;2-Q · DOI
  14. Chang, 1999, Efficacy and safety analyses of a recombinant human immunodeficiency virus type 1 derived vector system, Gene Ther, 6, 715, 10.1038/sj.gt.3300895 · DOI
  15. Sastry, 2005, Product-enhanced reverse transcriptase assay for replication-competent retrovirus and lentivirus detection, Hum Gene Ther, 16, 1227, 10.1089/hum.2005.16.1227 · DOI
  16. Miskin, 2006, A replication competent lentivirus (RCL) assay for equine infectious anaemia virus (EIAV)-based lentiviral vectors, Gene Ther, 13, 196, 10.1038/sj.gt.3302666 · DOI
  17. Escarpe, 2003, Development of a sensitive assay for detection of replication-competent recombinant lentivirus in large-scale HIV-based vector preparations, Mol Ther, 8, 332, 10.1016/S1525-0016(03)00167-9 · DOI
  18. Sastry, 2003, Certification assays for HIV-1-based vectors: frequent passage of gag sequences without evidence of replication-competent viruses, Mol Ther, 8, 830, 10.1016/j.ymthe.2003.08.003 · DOI
  19. Manilla, 2005, Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector, Hum Gene Ther, 16, 17, 10.1089/hum.2005.16.17 · DOI
  20. Li, 2005, Long-term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy, Mol Ther, 12, 900, 10.1016/j.ymthe.2005.07.524 · DOI
  21. DiGiusto, 2010, RNA-based gene therapy for HIV with lentiviral vector-modified CD34(+) cells in patients undergoing transplantation for AIDS-related lymphoma, Sci Transl Med, 2, 36ra43, 10.1126/scitranslmed.3000931 · DOI
  22. Cornetta, 1993, Infection of human cells with murine amphotropic replication-competent retroviruses, Hum Gene Ther, 4, 579, 10.1089/hum.1993.4.5-579 · DOI
  23. Muenchau, 1990, Analysis of retroviral packaging lines for generation of replication-competent virus, Virology, 176, 262, 10.1016/0042-6822(90)90251-L · DOI
  24. Bodine, 1990, Development of a high-titer retrovirus producer cell line capable of gene transfer into rhesus monkey hematopoietic stem cells, Proc Natl Acad Sci USA, 87, 3738, 10.1073/pnas.87.10.3738 · DOI
  25. Scarpa, 1991, Characterization of recombinant helper retroviruses from Moloney-based vectors in ecotropic and amphotropic packaging cell lines, Virology, 180, 849, 10.1016/0042-6822(91)90105-K · DOI
  26. Otto, 1994, Characterization of a replication-competent retrovirus resulting from recombination of packaging and vector sequences, Hum Gene Ther, 5, 567, 10.1089/hum.1994.5.5-567 · DOI
  27. Bosselman, 1987, Replication-defective chimeric helper proviruses and factors affecting generation of competent virus: expression of Moloney murine leukemia virus structural genes via the metallothionein promoter, Mol Cell Biol, 7, 1797, 10.1128/MCB.7.5.1797 · DOI
  28. Markowitz, 1988, A safe packaging line for gene transfer: separating viral genes on two different plasmids, J Virol, 62, 1120, 10.1128/JVI.62.4.1120-1124.1988 · DOI
  29. Markowitz, 1988, Construction and use of a safe and efficient amphotropic packaging cell line, Virology, 167, 400, 10.1016/S0042-6822(88)90101-8 · DOI
  30. Danos, 1988, Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges, Proc Natl Acad Sci USA, 85, 6460, 10.1073/pnas.85.17.6460 · DOI
  31. Miller, 1989, Improved retroviral vectors for gene transfer and expression, BioTechniques, 7, 980
  32. Miller, 1991, Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus, J Virol, 65, 2220, 10.1128/JVI.65.5.2220-2224.1991 · DOI
  33. Chong, 1998, A replication-competent retrovirus arising from a split-function packaging cell line was generated by recombination events between the vector, one of the packaging constructs, and endogenous retroviral sequences, J Virol, 72, 2663, 10.1128/JVI.72.4.2663-2670.1998 · DOI
  34. Garrett, 2000, Characterization of recombination events leading to the production of an ecotropic replication-competent retrovirus in a GP+envAM12-derived producer cell line, Virology, 266, 170, 10.1006/viro.1999.0052 · DOI
  35. Amado, 1999, Lentiviral vectors–the promise of gene therapy within reach?, Science, 285, 674, 10.1126/science.285.5428.674 · DOI
  36. Blömer, 1997, Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector, J Virol, 71, 6641, 10.1128/JVI.71.9.6641-6649.1997 · DOI
  37. Lever, 2000, Lentiviral vectors: progress and potential, Curr Opin Mol Ther, 2, 488
  38. Podsakoff, 2001, Lentiviral vectors approach the clinic but fall back: National Institutes of Health Recombinant DNA Advisory Committee review of a first clinical protocol for use of a lentiviral vector, Mol Ther, 4, 282, 10.1006/mthe.2001.0470 · DOI
  39. Watson, 2002, Targeted transduction patterns in the mouse brain by lentivirus vectors pseudotyped with VSV, Ebola, Mokola, LCMV, or MuLV envelope proteins, Mol Ther, 5, 528, 10.1006/mthe.2002.0584 · DOI
  40. Li, 2002, Murine leukemia induced by retroviral gene marking, Science, 296, 497, 10.1126/science.1068893 · DOI
  41. Hacein-Bey-Abina, 2003, LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1, Science, 302, 415, 10.1126/science.1088547 · DOI · Paper page
  42. Ott, 2006, Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1, Nat Med, 12, 401, 10.1038/nm1393 · DOI
  43. Nienhuis, 2006, Genotoxicity of retroviral integration in hematopoietic cells, Mol Ther, 13, 1031, 10.1016/j.ymthe.2006.03.001 · DOI
  44. Transfiguracion, 2003, Size-exclusion chromatography purification of high-titer vesicular stomatitis virus G glycoprotein-pseudotyped retrovectors for cell and gene therapy applications, Hum Gene Ther, 14, 1139, 10.1089/104303403322167984 · DOI
  45. Segura, 2007, Production of lentiviral vectors by large-scale transient transfection of suspension cultures and affinity chromatography purification, Biotechnol Bioeng, 98, 789, 10.1002/bit.21467 · DOI
  46. Slepushkin, 2003, Large-scale purification of a lentiviral vector by size exclusion chromatography or mustang Q ion exchange capsule, Bioprocessing J, 89
  47. Kutner, 2009, Production, concentration and titration of pseudotyped HIV-1-based lentiviral vectors, Nat Protoc, 4, 495, 10.1038/nprot.2009.22 · DOI
  48. Scherr, 2002, Efficient gene transfer into the CNS by lentiviral vectors purified by anion exchange chromatography, Gene Ther, 9, 1708, 10.1038/sj.gt.3301848 · DOI
  49. Merten, 2010, Large scale manufacture and characterisation of a lentiviral vector produced for clinical ex vivo gene therapy application, Hum Gene Ther
  50. Sastry, 2004, Evaluation of plasmid DNA removal from lentiviral vectors by benzonase treatment, Hum Gene Ther, 15, 221, 10.1089/104303404772680029 · DOI

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Metadata

Authors
Cornetta, K., Yao, J., Jasti, A., Koop, S., Douglas, M., Hsu, D., Couture, L. A., Hawkins, T., & Duffy, L.
Affiliations
  • Indiana University Indianapolis (US)
  • City Of Hope National Medical Center (US)
Corresponding author
Cornetta, Kenneth
ORCID
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2011-03
Volume
19
Issue
3
Pages
557-566
ISSN
1525-0016 (ISSN-L)
DOI
10.1038/mt.2010.278
PMC
PMC3048188
OpenAlex
W2065266863
Cited by
55
References
1
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 7 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 8
FWCI
2.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Lilly Endowment
  • National Heart, Lung, and Blood Institute (P40HL116242, T32HL007910)
  • National Center for Research Resources (U42RR011148, U42 RR11148, P40RR024928)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
Keywords
lentiviral vectors, recombination, vector production, clinical gene therapy
MeSH terms
Cell Line, Enzyme-Linked Immunosorbent Assay, Genetic Vectors, Humans, Quality Control, Recombination, Genetic, Reference Standards, Sensitivity and Specificity, Virus Replication, Reproducibility of Results, Lentivirus, HIV Core Protein p24, HEK293 Cells

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