Correction of murine rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene

Molecular Therapy

Volumn 20, Issue 10, 2012, Pages 1968-1980

  Van Til, Niek P ^a   De Boer, Helen ^a   Mashamba, Nomusa ^a   Wabik, Agnieszka ^a   Huston, Marshall ^a   Visser, Trudi P ^a   Fontana, Elena ^b   Poliani, Pietro Luigi ^b   Cassani, Barbara ^c   Zhang, Fang ^d   Thrasher, Adrian J ^d,e   Villa, Anna ^f,g   Wagemaker, Gerard ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b UNIVERSITY OF BRESCIA   (Italy)

^c HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

^e GREAT ORMOND STREET HOSPITAL   (United Kingdom)

^f CNR   (Italy)

^g SAN RAFFAELE SCIENTIFIC INSTITUTE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN; LENTIVIRUS VECTOR; RAG2 PROTEIN; T LYMPHOCYTE RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY RESPONSE; ARTICLE; B LYMPHOCYTE; CODON; CONTROLLED STUDY; FEMALE; GENE TRANSFER; IMMUNOGLOBULIN BLOOD LEVEL; MITOGENESIS; MOUSE; NONHUMAN; PROMOTER REGION; RAG2 GENE; SEVERE COMBINED IMMUNODEFICIENCY; SPLEEN FOCUS FORMING VIRUS; T LYMPHOCYTE; TOXICITY TESTING; TRANSGENE; UBIQUITOUS CHROMATIN OPENING ELEMENT; VIRAL GENE DELIVERY SYSTEM;

MURINAE; MUS; SPLEEN FOCUS-FORMING VIRUS;

EID: 84867013112     PISSN: 15250016     EISSN: 15250024     Source Type: Journal    
DOI: 10.1038/mt.2012.110     Document Type: Article

References (47)

1. Smith, AR, Gross, TG and Baker, KS (2010). Transplant outcomes for primary immunodefciency disease. Semin Hematol 47: 79-85.
2. Cavazzana-Calvo, M, Hacein-Bey, S, de Saint Basile, G, Gross, F, Yvon, E, Nusbaum, P et al. (2000). Gene therapy of human severe combined immunodefciency (SCID)-X1 disease. Science 288: 669-672.
3. Hacein-Bey-Abina, S, Le Deist, F, Carlier, F, Bouneaud, C, Hue, C, De Villartay, JP et al. (2002). Sustained correction of X-linked severe combined immunodefciency by ex vivo gene therapy. N Engl J Med 346: 1185-1193.
4. Gaspar, HB, Parsley, KL, Howe, S, King, D, Gilmour, KC, Sinclair, J et al. (2004). Gene therapy of X-linked severe combined immunodefciency by use of a pseudotyped gammaretroviral vector. Lancet 364: 2181-2187.
5. Aiuti, A, Cattaneo, F, Galimberti, S, Benninghoff, U, Cassani, B, Callegaro, L et al. (2009). Gene therapy for immunodefciency due to adenosine deaminase defciency. N Engl J Med 360: 447-458.
6. Hacein-Bey-Abina, S, Garrigue, A, Wang, GP, Soulier, J, Lim, A, Morillon, E et al. (2008). Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 118: 3132-3142.
7. Howe, SJ, Mansour, MR, Schwarzwaelder, K, Bartholomae, C, Hubank, M, Kempski, H 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.
8. Tonegawa, S (1983). Somatic generation of antibody diversity. Nature 302: 575-581.
9. -/- mice: sustained correction of the immunodefciency. Blood 100: 3942-3949.
10. Robbins, PB, Skelton, DC, Yu, XJ, Halene, S, Leonard, EH and Kohn, DB (1998). Consistent, persistent expression from modifed retroviral vectors in murine hematopoietic stem cells. Proc Natl Acad Sci USA 95: 10182-10187.
11. Pike-Overzet, K, Rodijk, M, Ng, YY, Baert, MR, Lagresle-Peyrou, C, Schambach, A et al. (2011). Correction of murine Rag1 defciency by self-inactivating lentiviral vector-mediated gene transfer. Leukemia 25: 1471-1483.
12. Huston, MW, van Til, N P, Visser, TP, Arshad, S, Brugman, MH, Cattoglio, C et al. (2011). Correction of murine SCID-X1 by lentiviral gene therapy using a codon-optimized IL2RG gene and minimal pretransplant conditioning. Mol Ther 19: 1867-1877.
13. Moreno-Carranza, B, Gentsch, M, Stein, S, Schambach, A, Santilli, G, Rudolf, E et al. (2009). Transgene optimization signifcantly improves SIN vector titers, gp91phox expression and reconstitution of superoxide production in X-CGD cells. Gene Ther 16: 111-118.
14. Zhang, F, Frost, AR, Blundell, M P, Bales, O, Antoniou, MN and Thrasher, AJ (2010). A ubiquitous chromatin opening element (UCOE) confers resistance to DNA methylation-mediated silencing of lentiviral vectors. Mol Ther 18: 1640-1649.
15. Zarrin, AA, Fong, I, Malkin, L, Marsden, PA and Berinstein, NL (1997). Cloning and characterization of the human recombination activating gene 1 (RAG1) and RAG2 promoter regions. J Immunol 159: 4382-4394.
16. Fong, IC, Zarrin, AA, Wu, GE and Berinstein, NL (2000). Functional analysis of the human RAG 2 promoter. Mol Immunol 37: 391-402.
17. Markiewicz, S, Bosselut, R, Le Deist, F, de Villartay, J P, Hivroz, C, Ghysdael, J et al. (1996). Tissue-specifc activity of the gammac chain gene promoter depends upon an Ets binding site and is regulated by GA-binding protein. J Biol Chem 271: 14849-14855.
18. Zhang, F, Thornhill, SI, Howe, SJ, Ulaganathan, M, Schambach, A, Sinclair, J et al. (2007). Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells. Blood 110: 1448-1457.
19. Montini, E, Cesana, D, Schmidt, M, Sanvito, F, Ponzoni, M, Bartholomae, C 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.
20. Modlich, U, Navarro, S, Zychlinski, D, Maetzig, T, Knoess, S, Brugman, MH et al. (2009). Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol Ther 17: 1919-1928.
21. Montini, E, Cesana, D, Schmidt, M, Sanvito, F, Bartholomae, CC, Ranzani, M 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.
22. Pannetier, C, Cochet, M, Darche, S, Casrouge, A, Zöller, M and Kourilsky, P (1993). The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. Proc Natl Acad Sci USA 90: 4319-4323.
23. Li, Z, Dordai, DI, Lee, J and Desiderio, S (1996). A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle. Immunity 5: 575-589.
24. Lee, PP, Fitzpatrick, DR, Beard, C, Jessup, HK, Lehar, S, Makar, KW et al. (2001). A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15: 763-774.
25. Zhou, S, Mody, D, DeRavin, SS, Hauer, J, Lu, T, Ma, Z et al. (2010). A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells. Blood 116: 900-908.
26. Villa, A, Sobacchi, C, Notarangelo, LD, Bozzi, F, Abinun, M, Abrahamsen, TG et al. (2001). V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodefciency with a spectrum of clinical presentations. Blood 97: 81-88.
27. Marrella, V, Poliani, PL, Casati, A, Rucci, F, Frascoli, L, Gougeon, ML et al. (2007). A hypomorphic R229Q Rag2 mouse mutant recapitulates human Omenn syndrome. J Clin Invest 117: 1260-1269.
28. Cassani, B, Poliani, PL, Marrella, V, Schena, F, Sauer, AV, Ravanini, M et al. (2010). Homeostatic expansion of autoreactive immunoglobulin-secreting cells in the Rag2 mouse model of Omenn syndrome. J Exp Med 207: 1525-1540.
29. Lagresle-Peyrou, C, Yates, F, Malassis-Séris, M, Hue, C, Morillon, E, Garrigue, A et al. (2006). Long-term immune reconstitution in RAG-1-defcient mice treated by retroviral gene therapy: a balance between effciency and toxicity. Blood 107: 63-72.
30. Fugmann, SD (2010). The origins of the Rag genes-from transposition to V(D)J recombination. Semin Immunol 22: 10-16.
31. Lee, J and Desiderio, S (1999). Cyclin A/CDK2 regulates V(D)J recombination by coordinating RAG-2 accumulation and DNA repair. Immunity 11: 771-781.
32. Sleckman, B P, Bassing, CH, Bardon, CG, Okada, A, Khor, B, Bories, JC et al. (1998). Accessibility control of variable region gene assembly during T-cell development. Immunol Rev 165: 121-130.
33. Boztug, K, Schmidt, M, Schwarzer, A, Banerjee, P P, Díez, IA, Dewey, RA et al. (2010). Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N Engl J Med 363: 1918-1927.
34. Stein, S, Ott, MG, Schultze-Strasser, S, Jauch, A, Burwinkel, B, Kinner, A 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.
35. Modlich, U, Bohne, J, Schmidt, M, von Kalle, C, Knöss, S, Schambach, A et al. (2006). Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity. Blood 108: 2545-2553.
36. Zychlinski, D, Schambach, A, Modlich, U, Maetzig, T, Meyer, J, Grassman, E et al. (2008). Physiological promoters reduce the genotoxic risk of integrating gene vectors. Mol Ther 16: 718-725.
37. Maruggi, G, Porcellini, S, Facchini, G, Perna, SK, Cattoglio, C, Sartori, D et al. (2009). Transcriptional enhancers induce insertional gene deregulation independently from the vector type and design. Mol Ther 17: 851-856.
38. Anliker, B, Abel, T, Kneissl, S, Hlavaty, J, Caputi, A, Brynza, J et al. (2010). Specifc gene transfer to neurons, endothelial cells and hematopoietic progenitors with lentiviral vectors. Nat Methods 7: 929-935.
39. van Til, N P, Stok, M, Aerts Kaya, FS, de Waard, MC, Farahbakhshian, E, Visser, TP et al. (2010). Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype. Blood 115: 5329-5337.
40. Dull, T, Zufferey, R, Kelly, M, Mandel, RJ, Nguyen, M, Trono, D et al. (1998). A third-generation lentivirus vector with a conditional packaging system. J Virol 72: 8463-8471.
41. Zufferey, R, Dull, T, Mandel, RJ, Bukovsky, A, Quiroz, D, Naldini, L et al. (1998). Self-inactivating lentivirus vector for safe and effcient in vivo gene delivery. J Virol 72: 9873-9880.
42. van Til, N P, Markusic, DM, van der Rijt, R, Kunne, C, Hiralall, JK, Vreeling, H et al. (2005). Kupffer cells and not liver sinusoidal endothelial cells prevent lentiviral transduction of hepatocytes. Mol Ther 11: 26-34.
43. -/- mice: functional inactivation of p53 in developing T cells. Blood 104: 3886-3893.
44. Shinkai, Y, Rathbun, G, Lam, KP, Oltz, EM, Stewart, V, Mendelsohn, M et al. (1992). RAG-2-defcient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68: 855-867.
45. -/- mice. Eur J Immunol 39: 2136-2145.
46. Pasqual, N, Gallagher, M, Aude-Garcia, C, Loiodice, M, Thuderoz, F, Demongeot, J et al. (2002). Quantitative and qualitative changes in V-J alpha rearrangements during mouse thymocytes differentiation: implication for a limited T cell receptor alpha chain repertoire. J Exp Med 196: 1163-1173.
47. Shaw, RJ, Liloglou, T, Rogers, SN, Brown, JS, Vaughan, ED, Lowe, D et al. (2006). Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing. Br J Cancer 94: 561-568.