Deletion of the LTR Enhancer/Promoter Has No Impact on the Integration Profile of MLV Vectors in Human Hematopoietic Progenitors

PLoS ONE

Volumn 8, Issue 1, 2013, Pages

  Moiani, Arianna ^a   Miccio, Annarita ^b   Rizzi, Ermanno ^c   Severgnini, Marco ^c   Pellin, Danilo ^d   Suerth, Julia Debora ^e   Baum, Christopher ^e   de Bellis, Gianluca ^c   Mavilio, Fulvio ^b,f  

^a SAN RAFFAELE HOSPITAL   (Italy)

^b UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^c INSTITUTE OF BIOMEDICAL TECHNOLOGIES   (Italy)

^d VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^e HANNOVER MEDICAL SCHOOL   (Germany)

^f GÉNÉTHON   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CD34 ANTIGEN; HISTONE H2AZ; HISTONE H3; RNA POLYMERASE II; SELF INACTIVATING VECTOR; UNCLASSIFIED DRUG; VIRUS VECTOR;

ARTICLE; CHROMATIN CONDENSATION; CONTROLLED STUDY; DNA SEQUENCE; ENHANCER REGION; GENE CLUSTER; GENE DELETION; GENOME ANALYSIS; HEMATOPOIETIC STEM CELL; HISTONE MODIFICATION; HUMAN; HUMAN CELL; LONG TERMINAL REPEAT; MOLONEY LEUKEMIA ONCOVIRUS; NONHUMAN; PROMOTER REGION; VIRUS CELL INTERACTION; VIRUS DNA CELL DNA INTERACTION; WILD TYPE;

ANIMALS; COMPUTATIONAL BIOLOGY; GENETIC LOCI; GENETIC VECTORS; GENOME, HUMAN; HEMATOPOIETIC STEM CELLS; HISTONES; HUMANS; MICE; MOLONEY MURINE LEUKEMIA VIRUS; MUTAGENESIS, INSERTIONAL; PROMOTER REGIONS, GENETIC; SEQUENCE DELETION; TERMINAL REPEAT SEQUENCES; TRANSDUCTION, GENETIC; VIRUS INTEGRATION;

EID: 84873154367     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0055721     Document Type: Article

References (41)

1. Coffin JM, Huges SH, Varmus HE (1997) Retroviruses. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
2. Bushman F, Lewinski M, Ciuffi A, Barr S, Leipzig J, et al. (2005) Genome-wide analysis of retroviral DNA integration. Nat Rev Microbiol 3: 848-858.
3. Cattoglio C, Facchini G, Sartori D, Antonelli A, Miccio A, et al. (2007) Hot spots of retroviral integration in human CD34+ hematopoietic cells. Blood 110: 1770-1778.
4. Cattoglio C, Pellin D, Rizzi E, Maruggi G, Corti G, et al. (2010) High-definition mapping of retroviral integration sites identifies active regulatory elements in human multipotent hematopoietic progenitors. Blood 116: 5507-5517.
5. Wang GP, Ciuffi A, Leipzig J, Berry CC, Bushman FD, (2007) HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications. Genome Res 17: 1186-1194.
6. Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, et al. (2009) Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med 360: 447-458.
7. Hacein-Bey-Abina S, Le Deist F, Carlier F, Bouneaud C, Hue C, et al. (2002) Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med 346: 1185-1193.
8. Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Diez IA, et al. (2010) Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N Engl J Med 363: 1918-1927.
9. Mavilio F, Pellegrini G, Ferrari S, Di Nunzio F, Di Iorio E, et al. (2006) Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med 12: 1397-1402.
10. Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, et al. (2009) Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326: 818-823.
11. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, et al. (2008) Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 118: 3132-3142.
12. Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, et al. (2008) Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest 118: 3143-3150.
13. Krause D, (2011) Gene Therapy for Wiskott-Aldrich Syndrome: Benefits and Risks. The Hematologist 8: 10.
14. Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, et al. (2006) Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med 12: 401-409.
15. Stein S, Ott MG, Schultze-Strasser S, Jauch A, Burwinkel B, et al. (2010) Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med 16: 198-204.
16. Zychlinski D, Schambach A, Modlich U, Maetzig T, Meyer J, et al. (2008) Physiological Promoters Reduce the Genotoxic Risk of Integrating Gene Vectors. Mol Ther.
17. Maruggi G, Porcellini S, Facchini G, Perna SK, Cattoglio C, et al. (2009) Transcriptional Enhancers Induce Insertional Gene Deregulation Independently From the Vector Type and Design. Mol Ther 17: 851-856.
18. Modlich U, Navarro S, Zychlinski D, Maetzig T, Knoess S, et al. (2009) Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol Ther 17: 1919-1928.
19. Montini E, Cesana D, Schmidt M, Sanvito F, Bartholomae CC, et al. (2009) The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J Clin Invest 119: 964-975.
20. Felice B, Cattoglio C, Cittaro D, Testa A, Miccio A, et al. (2009) Transcription factor binding sites are genetic determinants of retroviral integration in the human genome. PLoS ONE 4: e4571.
21. Thornhill SI, Schambach A, Howe SJ, Ulaganathan M, Grassman E, et al. (2008) Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiency. Mol Ther 16: 590-598.
22. Kim SY, Pritchard JK, (2007) Adaptive evolution of conserved noncoding elements in mammals. PLoS Genet 3: 1572-1586.
23. Cattoglio C, Maruggi G, Bartholomae C, Malani N, Pellin D, et al. (2010) High-definition mapping of retroviral integration sites defines the fate of allogeneic T cells after donor lymphocyte infusion. PLoS One 5: e15688.
24. Cui K, Zang C, Roh TY, Schones DE, Childs RW, et al. (2009) Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell Stem Cell 4: 80-93.
25. Wang GP, Levine BL, Binder GK, Berry CC, Malani N, et al. (2009) Analysis of lentiviral vector integration in HIV+ study subjects receiving autologous infusions of gene modified CD4+ T cells. Mol Ther 17: 844-850.
26. Engelman A, Cherepanov P, (2008) The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS Pathog 4: e1000046.
27. Lewinski MK, Yamashita M, Emerman M, Ciuffi A, Marshall H, et al. (2006) Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog 2: e60.
28. Creyghton MP, Markoulaki S, Levine SS, Hanna J, Lodato MA, et al. (2008) H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell 135: 649-661.
29. Studamire B, Goff SP, (2008) Host proteins interacting with the Moloney murine leukemia virus integrase: multiple transcriptional regulators and chromatin binding factors. Retrovirology 5: 48.
30. Kustikova O, Fehse B, Modlich U, Yang M, Dullmann J, et al. (2005) Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science 308: 1171-1174.
31. Modlich U, Kustikova OS, Schmidt M, Rudolph C, Meyer J, et al. (2005) Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesis. Blood 105: 4235-4246.
32. Montini E, Cesana D, Schmidt M, Sanvito F, Ponzoni M, et al. (2006) Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat Biotechnol 24: 687-696.
33. Modlich U, Bohne J, Schmidt M, von Kalle C, Knoss S, et al. (2006) Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity. Blood 108: 2545-2553.
34. Bosticardo M, Ghosh A, Du Y, Jenkins NA, Copeland NG, et al. (2009) Self-inactivating retroviral vector-mediated gene transfer induces oncogene activation and immortalization of primary murine bone marrow cells. Mol Ther 17: 1910-1918.
35. Kustikova O, Brugman M, Baum C, (2010) The genomic risk of somatic gene therapy. Semin Cancer Biol 20: 269-278.
36. Cavazzana-Calvo M, Payen E, Negre O, Wang G, Hehir K, et al. (2010) Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature 467: 318-322.
37. Almarza D, Bussadori G, Navarro M, Mavilio F, Larcher F, et al. (2011) Risk assessment in skin gene therapy: viral-cellular fusion transcripts generated by proviral transcriptional read-through in keratinocytes transduced with self-inactivating lentiviral vectors. Gene Ther 18: 674-681.
38. Cesana D, Sgualdino J, Rudilosso L, Merella S, Naldini L, et al. (2012) Whole transcriptome characterization of aberrant splicing events induced by lentiviral vector integrations. J Clin Invest 122: 1667-1676.
39. Heckl D, Schwarzer A, Haemmerle R, Steinemann D, Rudolph C, et al. (2012) Lentiviral vector induced insertional haploinsufficiency of Ebf1 causes murine leukemia. Mol Ther 20: 1187-1195.
40. Moiani A, Paleari Y, Sartori D, Mezzadra R, Miccio A, et al. (2012) Lentiviral vector integration in the human genome induces alternative splicing and generates aberrant transcripts. J Clin Invest 122: 1653-1666.
41. Ye T, Krebs AR, Choukrallah MA, Keime C, Plewniak F, et al. (2010) seqMINER: an integrated ChIP-seq data interpretation platform. Nucleic Acids Res 39: e35.