Hepatic lentiviral gene transfer is associated with clonal selection, but not with tumor formation in serially transplanted rodents

Hepatology

Volumn 58, Issue 1, 2013, Pages 397-408

  Rittelmeyer, Ina ^a,b   Rothe, Michael ^a,b   Brugman, Martijn H ^a,c   Iken, Marcus ^a,b   Schambach, Axel ^a,d   Manns, Michael P ^a   Baum, Christopher ^a   Modlich, Ute ^a,e   Ott, Michael ^a,b  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b INSTITUTE OF INFECTION IMMUNOLOGY   (Germany)

^c LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^d BOSTON CHILDREN S HOSPITAL   (United States)

^e PAUL EHRLICH INSTITUT   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

FUMARYLACETOACETASE; LENTIVIRUS VECTOR; NITISINONE;

ANIMAL CELL; ARTICLE; CARCINOGENESIS; CELL PROLIFERATION; CONTROLLED STUDY; GENE EXPRESSION; HEPATOCYTE TRANSPLANTATION; IN VIVO STUDY; LIVER CELL; LIVER TUMOR; MOUSE; MUTAGENESIS; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; VIRAL GENE DELIVERY SYSTEM;

ANIMALS; CLONE CELLS; GENE DOSAGE; GENETIC THERAPY; GENETIC VECTORS; HEPATOCYTES; HYDROLASES; LENTIVIRUS; LIVER NEOPLASMS; MICE; MICE, INBRED C57BL; POLYMERASE CHAIN REACTION;

EID: 84879607520     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.26204     Document Type: Article

References (49)

1. Ferry N, Pichard V, Sebastien Bony DA, Nguyen TH. Retroviral vector-mediated gene therapy for metabolic diseases: an update. Curr Pharm Des 2011; 17: 2516-2527.
2. Raper SE, Grossman M, Rader DJ, Thoene JG, Clark BJ 3rd, Kolansky DM, et al. Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia. Ann Surg 1996; 223: 116-126.
3. Grossman M, Rader DJ, Muller DW, Kolansky DM, Kozarsky K, Clark BJ 3rd, et al. A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia. Nat Med 1995; 1: 1148-1154.
4. Schambach A, Baum C. Clinical application of lentiviral vectors - concepts and practice. Curr Gene Ther 2008; 8: 474-482.
5. Kay MA, Glorioso JC, Naldini L. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med 2001; 7: 33-40.
6. Rothe M, Rittelmeyer I, Iken M, Rudrich U, Schambach A, Glage S, et al. Epidermal growth factor improves lentivirus vector gene transfer into primary mouse hepatocytes. Gene Ther 2012; 19: 425-434.
7. Nguyen TH, Bellodi-Privato M, Aubert D, Pichard V, Myara A, Trono D, et al. Therapeutic lentivirus-mediated neonatal in vivo gene therapy in hyperbilirubinemic Gunn rats. Mol Ther 2005; 12: 852-859.
8. Grinshpun A, Condiotti R, Waddington SN, Peer M, Zeig E, Peretz S, et al. Neonatal gene therapy of glycogen storage disease type Ia using a feline immunodeficiency virus-based vector. Mol Ther 2010; 18: 1592-1598.
9. Riviere I, Dunbar CE, Sadelain M. Hematopoietic stem cell engineering at a crossroads. Blood 2011; 119: 1107-1116.
10. Modlich U, Kustikova OS, Schmidt M, Rudolph C, Meyer J, Li Z, et al. Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesis. Blood 2005; 105: 4235-4246.
11. Montini E, Cesana D, Schmidt M, Sanvito F, Ponzoni M, Bartholomae C, et al. Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat Biotechnol 2006; 24: 687-696.
12. Li Z, Dullmann J, Schiedlmeier B, Schmidt M, von Kalle C, Meyer J, et al. Murine leukemia induced by retroviral gene marking. Science 2002; 296: 497.
13. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 2008; 118: 3132-3142.
14. Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest 2008; 118: 3143-3150.
15. Wu X, Li Y, Crise B, Burgess SM. Transcription start regions in the human genome are favored targets for MLV integration. Science 2003; 300: 1749-1751.
16. Modlich U, Navarro S, Zychlinski D, Maetzig T, Knoess S, Brugman MH, et al. Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol Ther 2009; 17: 1919-1928.
17. Montini E, Cesana D, Schmidt M, Sanvito F, Bartholomae CC, Ranzani M, et al. 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 2009; 119: 964-975.
18. Mitchell RS, Beitzel BF, Schroder AR, Shinn P, Chen H, Berry CC, et al. Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol 2004; 2: E234.
19. Beard BC, Dickerson D, Beebe K, Gooch C, Fletcher J, Okbinoglu T, et al. Comparison of HIV-derived lentiviral and MLV-based gammaretroviral vector integration sites in primate repopulating cells. Mol Ther 2007; 15: 1356-1365.
20. Hematti P, Hong BK, Ferguson C, Adler R, Hanawa H, Sellers S, et al. Distinct genomic integration of MLV and SIV vectors in primate hematopoietic stem and progenitor cells. PLoS Biol 2004; 2: e423.
21. Cavazzana-Calvo M, Payen E, Negre O, Wang G, Hehir K, Fusil F, et al. Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature 2010; 467: 318-322.
22. Heckl D, Schwarzer A, Haemmerle R, Steinemann D, Rudolph C, Skawran B, et al. Lentiviral vector induced insertional haploinsufficiency of Ebf1 causes murine leukemia. Mol Ther 2012; 20: 1187-1195.
23. Themis M, Waddington SN, Schmidt M, von Kalle C, Wang Y, Al-Allaf F, et al. Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice. Mol Ther 2005; 12: 763-771.
24. Figueiredo ML, Wentworth KM, Sandgren EP. Quantifying growth and transformation frequency of oncogene-expressing mouse hepatocytes in vivo. HEPATOLOGY 2010; 52: 634-643.
25. Grompe M, al-Dhalimy M, Finegold M, Ou CN, Burlingame T, Kennaway NG, et al. Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice. Genes Dev 1993; 7: 2298-2307.
26. Lindstedt S, Holme E, Lock EA, Hjalmarson O, Strandvik B. Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. Lancet 1992; 340: 813-817.
27. Grompe M, Lindstedt S, al-Dhalimy M, Kennaway NG, Papaconstantinou J, Torres-Ramos CA, et al. Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I. Nat Genet 1995; 10: 453-460.
28. Overturf K, Al-Dhalimy M, Tanguay R, Brantly M, Ou CN, Finegold M, et al. Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I. Nat Genet 1996; 12: 266-273.
29. Schambach A, Bohne J, Chandra S, Will E, Margison GP, Williams DA, et al. Equal potency of gammaretroviral and lentiviral SIN vectors for expression of O6-methylguanine-DNA methyltransferase in hematopoietic cells. Mol Ther 2006; 13: 391-400.
30. Kutner RH, Zhang XY, Reiser J. Production, concentration and titration of pseudotyped HIV-1-based lentiviral vectors. Nat Protoc 2009; 4: 495-505.
31. Schmidt M, Hoffmann G, Wissler M, Lemke N, Mussig A, Glimm H, et al. Detection and direct genomic sequencing of multiple rare unknown flanking DNA in highly complex samples. Hum Gene Ther 2001; 12: 743-749.
32. Kustikova OS, Modlich U, Fehse B. Retroviral insertion site analysis in dominant haematopoietic clones. Methods Mol Biol 2009; 506: 373-390.
33. Maetzig T, Brugman MH, Bartels S, Heinz N, Kustikova OS, Modlich U, et al. Polyclonal fluctuation of lentiviral vector-transduced and expanded murine hematopoietic stem cells. Blood 2011; 117: 3053-3064.
34. Klump H, Schiedlmeier B, Vogt B, Ryan M, Ostertag W, Baum C. Retroviral vector-mediated expression of HoxB4 in hematopoietic cells using a novel coexpression strategy. Gene Ther 2001; 8: 811-817.
35. Kustikova O, Fehse B, Modlich U, Yang M, Dullmann J, Kamino K, et al. Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science 2005; 308: 1171-1174.
36. Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U, et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med 2006; 12: 401-409.
37. Brugman MH, Suerth JD, Rothe M, Suerbaum S, Schambach A, Modlich U, et al. Evaluating a ligation-mediated PCR and pyrosequencing method for the detection of clonal contribution in polyclonal retrovirally transduced samples. Hum Gene Ther Methods 2013; 24: 68-79.
38. Modlich U, Schambach A, Brugman MH, Wicke DC, Knoess S, Li Z, et al. Leukemia induction after a single retroviral vector insertion in Evi1 or Prdm16. Leukemia 2008; 22: 1519-1528.
39. Brown BD, Cantore A, Annoni A, Sergi LS, Lombardo A, Della Valle P, et al. A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. Blood 2007; 110: 4144-4152.
40. Bayer M, Kantor B, Cockrell A, Ma H, Zeithaml B, Li X, et al. A large U3 deletion causes increased in vivo expression from a nonintegrating lentiviral vector. Mol Ther 2008; 16: 1968-1976.
41. Ranzani M, Cesana D, Bartholomae C, Sanvito F, Pala M, Benedicenti F, et al. Lentiviral vector-based insertional mutagenesis identifies new clinically relevant cancer genes involved in the pathogenesis of hepatocellular carcinoma. ESGCT abstract 2011.
42. Themis M, May D, Coutelle C, Newbold RF. Mutational effects of retrovirus insertion on the genome of V79 cells by an attenuated retrovirus vector: implications for gene therapy. Gene Ther 2003; 10: 1703-1711.
43. Donsante A, Miller DG, Li Y, Vogler C, Brunt EM, Russell DW, et al. AAV vector integration sites in mouse hepatocellular carcinoma. Science 2007; 317: 477.
44. Donsante A, Vogler C, Muzyczka N, Crawford JM, Barker J, Flotte T, et al. Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors. Gene Ther 2001; 8: 1343-1346.
45. Li H, Malani N, Hamilton SR, Schlachterman A, Bussadori G, Edmonson SE, et al. Assessing the potential for AAV vector genotoxicity in a murine model. Blood 2011; 117: 3311-3319.
46. Nathwani AC, Rosales C, McIntosh J, Rastegarlari G, Nathwani D, Raj D, et al. Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol Ther 2011; 19: 876-885.
47. Matrai J, Cantore A, Bartholomae CC, Annoni A, Wang W, Acosta-Sanchez A, et al. Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk. HEPATOLOGY 2011; 53: 1696-1707.
48. Biffi A, Bartolomae CC, Cesana D, Cartier N, Aubourg P, Ranzani M, et al. Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection. Blood 2011; 117: 5332-5339.
49. Weber K, Thomaschewski M, Warlich M, Volz T, Cornils K, Niebuhr B, et al. RGB marking facilitates multicolor clonal cell tracking. Nat Med 2011; 17: 504-509.