Insertional mutagenesis and development of malignancies induced by integrating gene delivery systems: Implications for the design of safer gene-based interventions in patients

Drug News and Perspectives

Volumn 22, Issue 4, 2009, Pages 185-196

  Romano, Gaetano ^a   Marino, Ignazio R ^a,b   Pentimalli, Francesca ^a,c   Adamo, Vincenzo ^e   Giordano, Antonio ^a,d  

^a Temple University   (United States)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

^c NATIONAL CANCER INSTITUTE   (Italy)

^d UNIVERSITY OF SIENA   (Italy)

^e UNIVERSITY OF MESSINA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ADALIMUMAB; ADENOVIRUS VECTOR; DNA; INTEGRASE; INTERLEUKIN 2 RECEPTOR; LENTIVIRUS VECTOR; PARVOVIRUS VECTOR; PLASMID DNA; RETROVIRUS VECTOR; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; VIRUS VECTOR; ZINC FINGER PROTEIN;

ADENO ASSOCIATED VIRUS; ADENOVIRUS; CARCINOGENESIS; CLINICAL TRIAL; EQUINE INFECTIOUS ANEMIA VIRUS; FELINE IMMUNODEFICIENCY VIRUS; GENE DELIVERY SYSTEM; GENE EXPRESSION REGULATION; GENE INSERTION; GENE MUTATION; GENE OVEREXPRESSION; GENE THERAPY; GENE TRANSFER; GENETIC TRANSDUCTION; HEMATOLOGIC MALIGNANCY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; LEUKEMIA; LMO2 ONCOGENE; MALIGNANT TRANSFORMATION; MYCOSIS; NONHUMAN; ONCOGENE; PROTO ONCOGENE; RETROVIRUS; REVIEW; RHEUMATOID ARTHRITIS; SEVERE COMBINED IMMUNODEFICIENCY X1; STEM CELL TRANSPLANTATION; STREPTOMYCES; TRANSGENE; VIRUS GENOME; X LINKED SEVERE COMBINED IMMUNODEFICIENCY;

ANIMALS; CLINICAL TRIALS AS TOPIC; GENE THERAPY; GENE TRANSFER TECHNIQUES; GENETIC VECTORS; HUMANS; MUTAGENESIS, INSERTIONAL; NEOPLASMS;

EID: 67651155881     PISSN: 02140934     EISSN: None     Source Type: Journal    
DOI: 10.1358/dnp.2009.22.4.1367704     Document Type: Review

References (116)

1. Edelstein, M.L., Abedi, M.R. and Wixon, J. Gene therapy clinical trials worldwide to 2007 - an update. J Gene Med 2007, 9(10): 833-842
2. Romano, G., Micheli, P., Pacilio, C. and Giordano, A. Latest developments in gene transfer technology: achievements, perspectives, and controversies over therapeutic applications. Stem Cells 2000, 18(1): 19-39. (Pubitemid 30064889)
3. Romano, G., Pacilio, C. and Giordano, A. Gene transfer technology in therapy: current applications and future goals. Stem Cells 1999, 17(4): 191-202. (Pubitemid 29350210)
4. Romano G. Gene transfer in experimental medicine. Drug News Perspect 2003, 16(5):267-276
5. Romano, G. Advances and perspectives in the field of gene transfer technology. Drug News Perspect 2006, 19(6): 359-368
6. Romano, G. Current development of nonviral-mediated gene transfer. Drug News Perspect 2007, 20(4): 227-231 (Pubitemid 47242191)
7. Edelstein, M.L., Abedi, M.R., Wixon, J. and Edelstein, R.M. Gene therapy clinical trials worldwide 1989-2004 - an overwiew. J Gene Med 2004, 6(6): 597-602.
8. Rosenberg, S.A., Aebersold, P., Cornetta, K. et al. Gene transfer into humans - immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 1990, 323(9): 570-578 (Pubitemid 20260084)
9. Blaese, R.M., Culver, K.W., Miller, A.D. et al. 7 lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science 1995; 270(5235): 475-480
10. Muul, L.M., Tuschong, L.M., Soenen, S.L. et al. Persistence and expression of the adenosine deaminase gene for 12 years and immune system reaction to gene transfer components: long-term results of the first clinical gene therapy trial. Blood 2003, 101(7): 2563-2569
11. Knorr, D. Serious adverse event on NIH human gene transfer protocol n. 9512-10139 A phase I study of adenovector mediated gene transfer to liver in adults with partial ornithine transcarbamylase deficiency. Memorandum of 21 September 1999, Office of Recombinant DNA activities at NIH.
12. Brenner, M. Gene therapy by adenovectors. Blood 1999; 94(12): 3965-3967
13. Romano, G. The controversial role of adenoviral-derived vectors in gene therapy: Where do we stand? Drug News Perspect 2006, 19(2): 99-106.
14. Kielian, T. and Hickey, W.F. Inflammatory thoughts about glioma gene therapy. Nat Med 1999, 5(11): 1237-1238 (Pubitemid 29535591)
15. Dewey, R.A., Morrissey, G., Cowsill, C.M. et al. Chronic brain inflammation and persistent herpes simplex virus type 1 thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: implications for clinical trials. Nat Med 1999, 5(11): 1256-1263 (Pubitemid 29535602)
16. Okimoto, T., Yahata, H., Itou, H. et al. Safety and growth suppressive effect of intra-hepatic arterial injection of AdCMV-p53 combined with CDDP to rat liver metastatic tumors. J Exp Clin Cancer Res 2003, 22(3): 399-406. (Pubitemid 37205396)
17. Anderson, W.F. Gene therapy scores against cancer. Nat Med 2000, 6(8): 862-863 (Pubitemid 30644739)
18. Marchisone, C., Pfeffer, U., Del Grosso, F. et al. Progress towards gene therapy for cancer. J Exp Clin Cancer Res 2000, 20: 5-10.
19. Khuri, F.R., Nemunaitis, J., Ganly, I. et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 1997, 3: 639-645.
20. Gan, D.D., Macaluso, M., Cinti, C. et al. How does a normal human cell become a cancer cell?) Exp Clin Cancer Res 2003, 22(4): 509-16. (Pubitemid 38222035)
21. Heise, C., Sampson-Johannes, A., Williams, A. et al. ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolisis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med 1997, 3(6): 639-645 (Pubitemid 27264973)
22. He, P., Tang, Z.Y., Ye, S.L. et al. The targeted expression of interleukin-2 in human hepatocellular carcinoma cells. J Exp Clin Cancer Res 2000, 19(2): 183-187 (Pubitemid 30490158)
23. Koyama, F., Sawada, H., Fujii H. et al. Enzyme/prodrug gene therapy for human colon cancer using adenovirus-mediated gene transfer of the Escherichia coli cytosine deaminase gene driven by a CAG promoter associated with 5-fluorocytosine administration. J Exp Clin Cancer Res 2000, 19(1): 75-80. (Pubitemid 30305524)
24. Zheng, Z., Takahashi, M., Aoki, S. et al. Expression of costimulatory molecules on cells derived from human hematological malignancies. J Exp Clin Cancer Res 1998, 17(3): 251-258 (Pubitemid 29090365)
25. Vasudevan, D.M. and Vijayakumar, T. Viruses In human oral cancers. J Exp Clin Cancer Res 1998, 17(1): 27-31.
26. Sullivan, N.J., Sanchez, A. and Rollin, P.E. Development of a preventive vaccine for Ebola virus infection in primates. Nature 2000, 408(6812): 605-609
27. Cavazzana-Calvo, M., Hacein-Bey, S., De Saint Basile, G. et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000, 288(5466): 669-672 (Pubitemid 30241569)
28. Anderson, W.F. The best of times, the worst of times. Science 2000, 288(5466): 627-629
29. Buckley, R.H. Gene therapy for human SCID: dreams become reality. Nat Med 2000, 6(6): 623-624
30. Marshall, E. Gene therapy a suspect in leukemia-like disease. Science 2002, 298(5591): 34-35
31. Buckley, R.H. Gene therapy for SCID - A complication after remarkable progress. Lancet 2002, 360(9341): 1185-1186
32. Check, E. Second cancer halts gene therapy clinical trials. Nature 2003, 421(6921): 305. (Pubitemid 36157908)
33. Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M. et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003, 302(5644): 415-419 (Pubitemid 37296260)
34. McCormack, M.P. and Rabbitts, T.H. Activation of the T-cell oncogene LMO2 after gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 2004, 350(9): 913-922 (Pubitemid 38252539)
35. Pike-Overzet, K., van der Burg, M., Wagemaker, G. et al. New insights and unresolved issues regarding insertional mutagenesis in X-linked SCID gene therapy. Mol Ther 2007, 15(11): 1910-1916
36. Cavazzana-Calvo, M. and Fischer, A. Gene therapy for severe combined immunodeficiency: are we there yet? J Clin Invest 2007, 117(6): 1456-1465 (Pubitemid 46871328)
37. Baum, C. What are the consequences of the fourth case? Mol Ther 2007, 15(8): 1401-1402
38. Hacein-Bey-Abina, S., Garrigue, A., Wang, G.P. et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 2008, 118(9): 3132-3142
39. Romano, G. An overview on gene therapy programs. Drug News Perspect 2008, 21(6): 345-351
40. Howe, S.J., Mansour, M.R., Schwarzwaelder, K. et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest 2008, 118(9): 3143-3150
41. Kaiser, J. Gene therapy: questions on cause of death in arthritis trial. Science 2007, 317(5845): 1665. (Pubitemid 47461809)
42. Wadman, M. Gene therapy might not have caused patient's death. Nature 2007, 449(7160): 270. (Pubitemid 47443453)
43. Kaiser, J. Clinical research. Death prompts a review of gene therapy vector. Science 2007, 317(5838): 580.
44. Romano, G. The standpoint of gene therapy programs. Drug News Perspect 2007, 20(5): 335-343
45. Romano, G. Current development of adeno-associated viral vectors. Drug News Perspect 2005, 18(5): 311-316 (Pubitemid 41491470)
46. Levine, B.L., Humeau, L.M., Boyer, J. et al. Dropulic, and C.H. June. Gene transfer in humans using a conditionally replicating lentiviral vector. Proc Natl Acad Sci U S A 2006, 103(46): 17372-17377
47. Romano, G. Current development of lentiviral-mediated gene transfer. Drug News Perspect 2005, 18(2): 128-134 (Pubitemid 40674902)
48. Romano, G., Claudio, P.P., Tonini, T. and Giordano, A. Human immunodeficiency virus type 1 (HIV-1) derived vectors: safety considerations and controversy over therapeutic applications. Eur J Dermatol 2003, 13(5): 424-429 (Pubitemid 37305084)
49. Romano, G. Stem cell transplantation therapy: controversy over ethical issues and clinical relevance. Drug News Perspect 2004, 17(10): 637-45. (Pubitemid 40224049)
50. Strulovici, Y., Leopold, P.L., O'Connor, T.P. et al. Human embryonic stem cells and gene therapy. Mol Ther 2007, 15(5): 850-866 (Pubitemid 46621644)
51. Goessler, U.R., Riedel, K., Hormann, K. et al. Perspectives of gene therapy in stem cell tissue engineering. Cells Tissues Organs 2006, 183(4): 169-179 (Pubitemid 44924465)
52. Sueblinvong, V., Suratt, B.T. and Weiss, D.J. Novel therapies for the treatment of cystic fibrosis: New developments in gene and stem cell biology. Clin Chest Med 2007, 28(2): 361-9. (Pubitemid 46654477)
53. Kimelman, N., Pelled, G., Helm, G.A. et al. Review: Gene-stem cell-based therapeutics for bone regeneration and repair. Tissue Eng 2007, 13(6): 1135-1150 (Pubitemid 46986715)
54. Korecka, J.A., Verhaagen, J. and Hol, E.M. Cell replacement and gene therapy strategies for Parkinson's and Alzheimer's disease. Regen Med 2007, 2(4): 425-446 (Pubitemid 47307222)
55. Ren, X., Tahimic, C.G., Katoh, M. et al. Human artificial chromosome vectors meet stem cells: New prospects for gene delivery. Stem Cell Rev 2006, 2(1): 43-50. (Pubitemid 44195977)
56. Quinonez, R. and Sutton, R.E. Lentiviral vectors for gene delivery into cells. DNA Cell Biol 2002, 21(12): 937-951 (Pubitemid 36126697)
57. Noguchi, P. Risks and benefits of gene therapy. N Engl J Med 2003, 348(3): 193-194
58. Takahashi, K., Tanabe, K., Ohnuki, M. et al. Induction of pluripotent stem cells from adult fibroblasts by defined factors. Cell 2007, 131(5): 861-872 (Pubitemid 350138099)
59. Yu, J., Vodyanik, M.A., Smuga-Otto, K. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007, 318(5858): 1917-1920
60. Hacein-Bey-Abina, S., von Kalle, C., Schmidt, M. et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 2003, 348(3): 255-256 (Pubitemid 36077924)
61. Dave, U.P., Jenkins, N.A. and Copeland, N.G. Gene therapy insertional mutagenesis insights. Science 2004, 303(5656): 333.
62. Woods, N.B., Bottera, V., Schmidt, M.et al. Therapeutic gene causing lymphoma. Nature 2006, 440(7988): 1123.
63. Giordano, A., Fucito, A., Romano, G. and Marino, I.R. Carcinogenesis and environment: The cancer stem cell hypothesis and implications for the development of novel therapeutics and diagnostics. Front Biosci 2007, 12: 3475-82.
64. Fucito, A., Lucchetti, C., Giordano, A. and Romano, G. Genetic and epigenetic alterations in beast cancer. What are the perspectives for clinical practice? Int J Biochem Cell Biol 2008, 40(4): 565-575
65. Pike-Overzet, K., de Ridder, D., Weerkamp, F. et al. Is IL2RG oncogenic in T-cell development? Nature 2006, 443(7109): E5.
66. Thrasher, A.J., Gaspar, H.B., Baum, C. et al. X-SCID transgene leukaemogenicity. Nature 2006(7109), 443: E5-E6.
67. Modlich, U., Schambach, A., Brugman, M.H. et al. Leukemia induction after a single retroviral vector insertion in Evi1 or Prdm16. Leukemia 2008, 22(8): 1519-1528
68. Chinen, J. and Puck, J.M. Successes and risks of gene therapy in primary immunodeficiencies. J Allergy Clin Immunol 2004, 113(4): 595-604. (Pubitemid 38530410)
69. Gaspar, H.B., Parsley, K.L., Howe, S. et al. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Lancet 2004, 364(9452): 2181-2187 (Pubitemid 40018447)
70. Ginn, S.L., Curtin, J.A., Kramer, B. et al. Treatment of an infant with X-linked severe combined immunodeficiency (SCID-X1) by gene therapy in Australia. Med J Aust 2005, 182(9): 458-463 (Pubitemid 40667812)
71. Chinen, J., Davis, J., De Ravin, S.S. et al. Gene therapy improves function in preadolescents with X-linked severe combined immunodeficiency. Blood 2007, 110(1): 67-73. (Pubitemid 47026820)
72. Schwarzwaelder, K., Howe, S.J., Schmidt, M. et al. Gammaretrovirus- mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo. J Clin Invest 2007, 117(8): 2241-2249 (Pubitemid 47219569)
73. Deichmann, A., Hacein-Bey-Abina, S., Schmidt, M. et al. Vector integration is norandorn and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy. J Clin Invest 2007, 117(8): 2225-2232 (Pubitemid 47219567)
74. Baum, C. Insertional mutagenesis in gene therapy and stem cell biology. Curr Opin Hematol 2007, 14(4): 337-342 (Pubitemid 46842807)
75. Modlich, U., Kustikova, O.S., Schmidt, M. et al. Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesis. Blood 2005, 105(11): 4235-4246
76. Kustikova, O., Fehse, B., Modlich, U. et al. Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science 2005, 308(5725): 1171-1174 (Pubitemid 40696434)
77. Mitchell, R.S., Beitzel, B.F., Schroder, A.R. et al. Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol 2004, 2(8): E234.
78. Lewinski, M.K., Yamashita, M., Emerman, M. et al. Retroviral DNA integration: Viral and cellular determinants of target-site selection. PLoS Pathog 2006, 2(6): E60. (Pubitemid 43998856)
79. Ciuffi, A., Mitchell, R.S., Hoffmann. C. et al. Integration site selection by HIV-based vectors in dividing and growth-arrested IMR-90 lung fibroblasts. Mol Ther 2006, 13(2): 366-373 (Pubitemid 43056902)
80. Schröder, A.R., Shinn, P., Chen, H. et al. HIV-1 integration in the human genome favors genes and local hotspots. Cell 2002, 110(4): 521-529 (Pubitemid 35232295)
81. Barr, S.D., Ciuffi, A., Leipzig, J. et al. HIV integration site selection: targeting in macrophages and the effects of different routes of viral entry. Mol Ther 2006, 14(2): 218-225 (Pubitemid 43942348)
82. Bester, A.C., Schwartz, M., Schmidt, M. et al. Fragile sites are preferential targets for integrations of MLV vectors in gene therapy. Gene Ther 2006, 13(13): 1057-1059 (Pubitemid 43905859)
83. Maxflield, L.F., Fraize, C.D., and Coffin, J.M. Relationship between retroviral DNA-integration-site selection and host cell transcription. Proc Natl Acad Sci U S A 2005, 102(5): 1436-41.
84. Donsante, A., Vogler, C., Muzyczka, N. et al. Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors. Gene Ther 2001, 8(17): 1343-1346 (Pubitemid 32834303)
85. Moldt, B., Yant, S.R., Andersen, P.R. et al. Cis-acting gene regulatory activities in the terminal regions of sleeping beauty DNA transposon-based vectors. Hum Gene Ther 2007, 18(12): 1193-1204 (Pubitemid 350261968)
86. Popescu, N.C. Genetic alterations in cancer: as a result of breakage at fragile sites. Cancer Lett 2003, 192(1): 1-17.
87. Freudenreich, C.H. Chromosome fragility: molecular mechanisms and cellular consequences. Front Biosci 2007, 12: 4911-4924
88. Padilla-Nash, H.M., Heselmeyer-Hadda, K., Wangsa, D. et al. Jumping translocations are common in solid tumor cell lines and result in recurrent fusions of whole chromosome arms. Genes Chromosomes Cancer 2001, 30(4): 349-353 (Pubitemid 32216326)
89. Smith, D.I., McAvoy, S., Zhu, Y. and Perez, D.S. Large common fragile site genes and cancer. Semin Cancer Biol 2007, 17(1): 31-41. (Pubitemid 46054484)
90. Zhang, F., Thornhill, S.I., Howe, S.J. et al. Lentiviral vectors containing an enhancer-less ubiquitously acting opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells. Blood 2007, 110(5): 1448-1457 (Pubitemid 47443959)
91. Schambach, A., Galla, M., Maetzig, T. et al. Improving transcriptional termination of self-inactivating gamma-retroviral and lentiviral vectors. Mol Ther 2007, 15(6): 1167-1173 (Pubitemid 46813620)
92. Felder, M.P., Eychene, A., Laugier, D. et al. Steps and mechanisms of oncogene transduction by retroviruses. Folia Biol (Praha) 1994, 40: 225-235 (Pubitemid 24359933)
93. Stocking, C., Kollk, R., Bergholz, U. and Ostertag, W. Long terminal repeat sequences impart transformation properties to the myeloproliferative sarcoma virus. Proc Natl Acad Sci U S A 1985, 82(17): 5746-5750
94. Lipsick, J.S. and Wang, D.M. Transformation by v-Myb. Oncogene 1999, 18(19): 3047-3055
95. Zaiss, A.K., Son, S., and Chang, L.J. RNA 3′ readthrough of oncoretrovirus and lentiviraus: implications for vector safety and efficacy. J Virol 2002, 76(14): 7209-7219
96. Gilmartin, G.M., Fleming, E.S. and Oertjen, J. Activation of HIV-1 pre-mRNA 3′ processing in vitro requires both an upstream element and TAR. EMBO J 1992, 11(12): 4419-4428
97. Philpott, N.J. and Thrasher, A.J. Use of nonintegrating lentiviral vectors for gene therapy. Hum Gene Ther 2007, 18(6): 483-489 (Pubitemid 47036043)
98. Philippe, S., Sarkis, C., Barkats, M. et al. Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo. Proc Natl Acad Sci U S A 2006, 103(47): 17684-17689 (Pubitemid 44852220)
99. Vargas, J., Jr., Gusella, G.L., Najfeld, V. et al. Novel integrase-defective lentiviral episomal vectors for gene therapy. Hum Gene Ther 2004, 15(4): 361-372 (Pubitemid 38469778)
100. Tarskikh, A.V., Ershler, M.A., Drize, N.J. et al. Long-term persistence of a nonintegrated letniviral vector in mouse hematopoietic stem cells. Exp Hematol 2005, 33(8): 873-882
101. Apolonia, L., Waddington, S.N., Fernandes, C. et al. Stable gene transfer to muscle using non-integrating lentiviral vectors. Mol Ther 2007, 15(11): 1947-1954 (Pubitemid 350011734)
102. Nightingale, S.J., Hollis, R.P., Pepper, K.A. et al. Transient gene expression by nonintegrating lentiviral vectors. Mol Ther 2006, 13(6): 1121-1132
103. Yanez-Munoz, R.J., Balaggan, K.S., MacNeil, A. et al. Effective gene therapy with nonintegrating lentiviral vectors. Nat Med 2006, 12(3): 348-353 (Pubitemid 43355085)
104. Baiker, A., Maercker, C., Piechaczek, C. et al. Mitotic stability of an episomal vector containing a human scaffold/matrix-attached region is provided by association with nuclear matrix. Nat Cell Biol 2000, 2(3): 182-184 (Pubitemid 30781135)
105. Lufino, M.M., Manservigi, R. and Wade-Martins, R. An S/MAR-based infectious episomal DNA expression vector provides long-term regulated functional complementation of LDLR deficiency. Nucleic Acids Res 2007, 35(15): e98.
106. Papapetrou, E.P., Ziros, P.G., Micheva, I.D. et al. Gene transfer into human hematopoietic progenitor cells with an episomal vector carrying an S/MAR element. Gene Ther 2006, 13(1): 40-51.
107. Dhanasekaran, M., Negi, S., Sugiura, Y. Designer zinc finger proteins: tools for creating artificial DNA-binding functional proteins. Acc Chem Res 2006, 39(1): 45-52.
108. Dent, C.L., Lau, G., Drake, E.A. et al. Regulation of endogenous gene expression using small molecule-controlled engineered zinc-finger protein transcription factors. Gene Ther 2007, 14(18): 1362-1369 (Pubitemid 47370846)
109. Dion, S., Demattéi, M.V., Renault, S. Zinc finger proteins: tools for site-specific correction or modification of the genome. Med Sci (Paris) 2007, 23: 834-839 (Pubitemid 350003965)
110. Verschure, P.J., Visser, A.E., Rots, M.G. Step out of the groove: epigenetic gene control systems and engineered transcription factors. Adv Genet 2006, 56: 163-204.
111. Pâques, F and Duchateau, P. Meganucleases and DNA double-strand break-induced recombination: perspectives for gene therapy. Curr Gene Ther 2007, 7(1): 49-66. (Pubitemid 46322288)
112. Iuchi, S. Three classes of C2H2 zinc finger proteins. Cell Mol Life Sci 2001, 58(4): 625-635
113. Smith, J., Grizot, S., Arnould, S. et al. A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences. Nucleic Acids Res 2006, 34(22): e149. (Pubitemid 46017964)
114. Arnould, S., Perez, C., Cabaniols, J.P. et al. Engineered I-Crel derivatives cleaving sequences from the human XPC gene can induce highly efficient gene correction in mammalian cells. J Mol Biol 2007, 371(1): 49-65. (Pubitemid 47030453)
115. Redondo, P., Prieto, J. and Muñoz I.G. Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases. Nature 2008, 456(7218): 107-111
116. Kraemer, K.H., Lee, M.M. and Scotto, J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol 1987, 123(2): 241-50.