Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo

Journal of Clinical Investigation

Volumn 117, Issue 8, 2007, Pages 2241-2249

  Schwarzwaelder, Kerstin ^a,b   Howe, Steven J ^c   Schmidt, Manfred ^a,b   Brugman, Martijn H ^d   Deichmann, Annette ^a,b   Glimm, Hanno ^a,b   Schmidt, Sonja ^b   Prinz, Claudia ^b   Wissler, Manuela ^b   King, Douglas J S ^c   Zhang, Fang ^c   Parsley, Kathryn L ^c,e   Gilmour, Kimberly C ^e   Sinclair, Joanna ^c   Bayford, Jinhua ^e   Peraj, Rachel ^e   Pike Overzet, Karin ^d   Staal, Frank J T ^d   De Ridder, Dick ^d,f   Kinnon, Christine ^c   Abel, Ulrich ^a,g   Wagemaker, Gerard ^d   Gaspar, H Bobby ^c,e   Thrasher, Adrian J ^c,e   Von Kalle, Christof ^a,b,h   more..

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b UNIVERSITY OF FREIBURG   (Germany)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d ERASMUS MEDICAL CENTER   (Netherlands)

^e GREAT ORMOND STREET HOSPITAL   (United Kingdom)

^f Delft University of Technology ^*  (Netherlands)

^g Tumor Center Heidelberg Mannheim   (Germany)

^h CINCINNATI CHILDREN S HOSPITAL RESEARCH FOUNDATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD3 ANTIGEN; CD34 ANTIGEN; GAMMARETROVIRUS VECTOR; IMMUNOGLOBULIN; RETROVIRUS VECTOR; UNCLASSIFIED DRUG;

ARTICLE; CELL PROLIFERATION; CELL SURVIVAL; CLINICAL ARTICLE; COMBINED IMMUNODEFICIENCY; DNA INTEGRATION; FEMALE; FOLLOW UP; GENE DELETION; GENE EXPRESSION PROFILING; GENETIC TRANSDUCTION; HUMAN; INFANT; MALE; OUTCOME ASSESSMENT; PRESCHOOL CHILD; PRIORITY JOURNAL; RETROVIRAL INTEGRATION SITE; STEM CELL; T LYMPHOCYTE; TRANSCRIPTION INITIATION SITE; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; X CHROMOSOME LINKED DISORDER;

ADULT; ANTIGENS, CD3; CELL PROLIFERATION; CELL SURVIVAL; CHILD; CHILD, PRESCHOOL; FEMALE; FOLLOW-UP STUDIES; GAMMARETROVIRUS; GENETIC VECTORS; GRAFT SURVIVAL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HEMATOPOIETIC STEM CELLS; HUMANS; INFANT; MALE; T-LYMPHOCYTES; TRANSDUCTION, GENETIC; TRANSPLANTATION, AUTOLOGOUS; VIRUS INTEGRATION; X-LINKED COMBINED IMMUNODEFICIENCY DISEASES;

EID: 34547651095     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI31661     Document Type: Article

References (31)

1. Cavazzana-Calvo, M., et al. 2000. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science. 288:669-672.
2. Gaspar, H.B., et al. 2004. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Lancet. 364:2181-2187.
3. Hacein-Bey-Abina, S., et al. 2002. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N. Engl. J. Med. 346:1185-1193.
4. Aiuti, A., et al. 2002. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science. 296:2410-2413.
5. Aiuti, A., et al. 2002. Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacement. Nat. Med. 8:423-425.
6. Gaspar, H.B., et al. 2006. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol. Ther. 14:505-513.
7. Ott, M.G., 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.
8. Hacein-Bey-Abina, S., et al. 2003. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 302:415-419.
9. Li, Z., et al. 2002. Murine leukemia induced by retroviral gene marking. Science. 296:497.
10. Kustikova, O., et al. 2005. Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science. 308:1171-1174.
11. Modlich, U., et al. 2005. Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesis. Blood. 105:4235-4246.
12. Montini, E., 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.
13. Mitchell, R.S., et al. 2004. Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol. 2:e234.
14. Schröder, A.R., et al. 2002. HIV-1 integration in the human genome favors active genes and local hotspots. Cell. 110:521-529.
15. Wu, X., Li, Y., Crise, B., and Burgess, S.M. 2003. Transcription start regions in the human genome are favored targets for MLV integration. Science. 300:1749-1751.
16. Bushman, F.D. 2003. Targeting survival: integration site selection by retroviruses and LTR-retrotransposons. Cell. 115:135-138.
17. Schmidt, M., et al. 2002. Polyclonal long-term repopulating stem cell clones in a primate model. Blood. 100:2737-2743.
18. + cells from the cord blood of ADA-deficient SCID neonates. Nat. Med. 9:463-468.
19. Hematti, P., et al. 2004. Distinct genomic integration of MLV and SIV vectors in primate hematopoietic stem and progenitor cells. PLoS Biol. 2:e423.
20. Laufs, S., et al. 2003. Retroviral vector integration occurs in preferred genomic targets in human bone marrow repopulating cells. Blood. 101:2191-2198.
21. Suzuki, T., et al. 2002. New genes involved in cancer identified by retroviral tagging. Nat. Genet. 32:166-174.
22. Bartholomew, C., and Ihle, J.N. 1991. Retroviral insertions 90 kilobases proximal to the Evi-1 myeloid transforming gene activate transcription from the normal promoter. Mol. Cell. Biol. 11:1820-1828.
23. Recchia, A., et al. 2006. Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells. Proc. Natl. Acad. Sci. U. S. A. 103:1457-1462.
24. Calmels, B., et al. 2005. Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells. Blood. 106:2530-2533.
25. Hoeben, R.C., Migchielsen, A.A., van der Jagt, R.C., van Ormondt, H., and van der Eb, A.J. 1991. Inactivation of the Moloney murine leukemia virus long terminal repeat in murine fibroblast cell lines is associated with methylation and dependent on its chromosomal position. J. Virol. 65:904-912.
26. Palmer, T.D., Rosman, G.J., Osborne, W.R., and Miller, A.D. 1991. Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc. Natl. Acad. Sci. U. S. A. 88:1330-1334.
27. Xu, L., Yee, J.K., Wolff, J.A., and Friedmann, T. 1989. Factors affecting long-term stability of Moloney murine leukemia virus-based vectors. Virology. 171:331-341.
28. Deichmann, A., et al. 2007. Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy. J. Clin. Invest. 117:2225-2232. doi:10.1172/JCI31659.
29. Dik, W.A., et al. 2005. New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling. J. Exp. Med. 201:1715-1723.
30. Ge, Y., Dudoit, S., and Speed, T.P. 2003. Resampling-based multiple testing for microarray analysis. Test. 12:1-77.
31. Armitage, P., Berry, G., and Matthews, J.N.S. 2001. Statistical methods in medical research. 4th edition. Blackwell Publishing. Malden, Massachusetts, USA/Oxford, United Kingdom. 832 pp.