Hepatic gene therapy using lentiviral vectors: Has safety been established?

Hepatology

Volumn 58, Issue 1, 2013, Pages 13-14

  Dismuke, David ^a   Samulski, R Jude ^b  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FUMARYLACETOACETASE; LENTIVIRUS VECTOR;

ARTICLE; CANCER RISK; CARCINOGENESIS; CARCINOGENICITY; CELL EXPANSION; CELL PROLIFERATION; CELL RENEWAL; CHRONIC LIVER DISEASE; CLONAL EXPANSION; GENE EXPRESSION; GENE THERAPY; GENE TRANSFER; GENETIC DAMAGE; GENOTOXICITY; HUMAN; LIVER CELL; LONG TERM SURVIVAL; MUTAGENESIS; PRIORITY JOURNAL; PROMOTER REGION; PYROSEQUENCING; SAFETY; THERAPY EFFECT;

ANIMALS; GENETIC THERAPY; HEPATOCYTES; HYDROLASES; LENTIVIRUS; LIVER NEOPLASMS;

EID: 84879556481     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.26460     Document Type: Article

References (20)

1. Alexander IE, Cunningham SC, Logan GJ, Christodoulou J. Potential of AAV vectors in the treatment of metabolic disease. Gene Ther 2008; 15: 831-839.
2. Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 2011; 365: 2357-2365.
3. Brunetti-Pierri N, Ng P. Helper-dependent adenoviral vectors for liver-directed gene therapy. Hum Mol Genet 2011; 20: R7-R13.
4. Gaspar HB, Parsley KL, Howe S, King D, Gilmour KC, Sinclair J, et al. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Lancet 2004; 364: 2181-2187.
5. Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC, et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 2010; 363: 355-364.
6. Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, Kutschera I, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 2009; 326: 818-823.
7. 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.
8. Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M, et al. T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science 1995; 270: 475-480.
9. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000; 288: 669-672.
10. 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.
11. 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.
12. 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.
13. Shou Y, Ma Z, Lu T, Sorrentino BP. Unique risk factors for insertional mutagenesis in a mouse model of XSCID gene therapy. Proc Natl Acad Sci U S A 2006; 103: 11730-11735.
14. 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.
15. 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.
16. 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.
17. Ronen K, Negre O, Roth S, Colomb C, Malani N, Denaro M, et al. Distribution of lentiviral vector integration sites in mice following therapeutic gene transfer to treat beta-thalassemia. Mol Ther 2011; 19: 1273-1286.
18. Schambach A, Zychlinski D, Ehrnstroem B, Baum C. Biosafety features of lentiviral vectors. Hum Gene Ther 2013; 24: 132-142.
19. Rittelmeyer I, Rothe M, Brugman MH, Iken M, Schambach A, Manns MP, et al. Hepatic lentiviral gene transfer is associated with clonal selection, but not with tumor formation in serially transplanted rodents. Hepatology 2013; 58: 397-408.
20. Gonzalez-Murillo A, Lozano ML, Montini E, Bueren JA, Guenechea G. Unaltered repopulation properties of mouse hematopoietic stem cells transduced with lentiviral vectors. Blood 2008; 112: 3138-3147.