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A Serious Adverse Event after Successful Gene Therapy for X-Linked Severe Combined Immunodeficiency
Abstract
To the Editor: We recently reported (April 18 issue)1 the sustained correction of X-linked severe combined immunodeficiency disease by ex vivo, retrovirally mediated transfer of the γc gene into CD34+ cells in four of five patients with the disease. These results have since been confirmed in four additional patients with typical X-linked severe combined immunodeficiency. Of the first four successfully treated patients, three continue to do well up to 3.6 years after gene therapy, whereas a serious adverse event occurred in the fourth patient. At a routine checkup 30 months after gene therapy, lymphocytosis consisting of a monoclonal population . . .
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“Lentiviral vectors are considered safer than gamma-retroviral vectors in terms of their semi-random integration patterns, as gene integration does not preferentially occur in start regions of active genes (93-95).”
From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [93]
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Hoelters, J., Karow, M., Drechsel, M., Geißler, C., Gülkan, H., Böcker, W., Schieker, M., Jochum, M., & Neth, P. (2005) · The Journal of Gene Medicine · doi:10.1002/jgm.731 · Cited by 81
Pattabhi, S., Lotti, S. N., Berger, M. P., Singh, S., Lux, C. T., Jacoby, K., Lee, C., Nègre, O., Scharenberg, A. M., & Rawlings, D. J. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.05.025 · Cited by 89
Adoptive immunotherapy for cancer
Ruella, M., & Kalos, M. D. (2013) · Immunological Reviews · doi:10.1111/imr.12136 · Cited by 160
“From an oncogenic perspective, significant early and justified concern about the oncogenic potential of retrovirus-based gene therapy as a result of the unfortunate report showing oncogenic transformation of stem cells due to retrovirus integration (223, 224) was mitigated initial in animal models (223, 225) and subse…”
ResultXMRV: A New Virus in Prostate Cancer?
Aloia, A. L., Sfanos, K. S., Isaacs, W. B., Zheng, Q., Maldarelli, F. M., Marzo, A. M. D., & Rein, A. R. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2837 · Cited by 76
“This mechanism of carcinogenesis has been observed not only in laboratory animals, but also in children exposed to gammaretrovirus-derived vectors in gene-therapy trials (22, 23).”
Brenner, S., & Malech, H. L. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(03)00024-7 · Cited by 74
Cancer Treatment with Gene Therapy and Radiation Therapy
Kaliberov, S. A., & Buchsbaum, D. J. (2012) · Advances in cancer research · doi:10.1016/b978-0-12-398342-8.00007-0 · Cited by 88
“Retroviruses continue to be employed as gene delivery vehicles, although recent adverse events following retroviral gene therapy have raised concerns about potential insertional mutagenesis (Hacein-Bey-Abina et al., 2003).”
Retroviral integration site selection
Desfarges, S., & Ciuffi, A. (2010) · Viruses · doi:10.3390/v2010111 · Cited by 78
“However, not all retroviruses display the same genotoxic potential, as gammaretroviruses for example appeared to be more prone to insertional mutagenesis than lentiviruses [33-37].”
BackgroundFigueroa, J. A., Reidy, A., Mirandola, L., Trotter, K., Suvorava, N., Figueroa, A., Konala, V., Aulakh, A., Littlefield, L., Grizzi, F., et al. (2015) · International Reviews of Immunology · doi:10.3109/08830185.2015.1018419 · Cited by 78
“Proviral DNA integration loci near transcriptional start sites may lead to proto-oncogene activation and have resulted in oncogenesis in viral-mediated gene modification of hematopoetic stem cells [146, 147].”
BackgroundThe changing face of adrenoleukodystrophy
Zhu, J., Eichler, F., Biffi, A., Duncan, C. N., Williams, D. A., & Majzoub, J. A. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa013 · Cited by 78
Cell and gene therapy for kidney disease
Peek, J. L., & Wilson, M. H. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00702-3 · Cited by 86
CAR-T Cell Therapies From the Transfusion Medicine Perspective
Fesnak, A. D., Lin, C., Siegel, D. L., & Maus, M. V. (2016) · Transfusion Medicine Reviews · doi:10.1016/j.tmrv.2016.03.001 · Cited by 86
“However, genomic integration represents a potential for malignant transformation of transduced cells that has been clinically observed in the case of gammaretroviruses [53] and remains a possibility with lentiviral vectors and, to a much lesser degree, DNA plasmid transfections.”
Noga, M., Edinger, D., Kläger, R., Wegner, S. V., Spatz, J. P., Wagner, E., Winter, G., & Besheer, A. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2012.12.025 · Cited by 87
Multifunctional nanocomplexes for gene transfer and gene therapy
Hart, S. L. (2010) · Cell Biology and Toxicology · doi:10.1007/s10565-009-9141-y · Cited by 71
Emerging strategies for cell and gene therapy of the muscular dystrophies
Muir, L. A., & Chamberlain, J. S. (2009) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399409001100 · Cited by 75
“Gene Therapy 12, 1099-1108 91 Hacein-Bey-Abina, S. et al. (2003) A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. New England Journal of Medicine 348, 255-256 92 Ciuffi, A. et al. (2006) Integration site selection by HIV-based vectors in dividing and growtharrested I…”
BackgroundInfluentialIn vivo biosafety model to assess the risk of adverse events from retroviral and lentiviral vectors.
Bauer, G., Dao, M., Case, S. S., Meyerrose, T., Wirthlin, L., Zhou, P., Wang, X.-L., Herrbrich, P. E., Arevalo, J., Csik, S., et al. (2008) · Molecular Therapy · doi:10.1038/mt.2008.93 · Cited by 77
Cui, M., Wan, Y.-Q., Anderson, D., Shen, F. H., Leo, B. M., Laurencin, C., Balian, G., & Li, X. (2008) · The spine journal · doi:10.1016/j.spinee.2007.05.012 · Cited by 77
Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase
Witte, I. P., Lampe, G. D., Eitzinger, S., Miller, S. M., Berríos, K. N., McElroy, A. N., King, R. T., Stringham, O. G., Gelsinger, D. R., Vo, P. L. H., et al. (2025) · Science · doi:10.1126/science.adt5199 · Cited by 121
“However, the clinical application of gene therapy has been limited by oncogenic DNA integration (21), the potential need for redosing (22), and immune responses to viral vectors (23).”
Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency
Shaw, K. L., Garabedian, E., Mishra, S., Barman, P., Davila, A., Carbonaro, D. A., Shupien, S., Silvin, C. J., Geiger, S., Nowicki, B., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90367 · Cited by 86
“Genotoxicity has been seen in other clinical trials for immune deficiencies (25–30) and was caused by vector integrations near cancer-related genes, such as LMO2 , CCND2 , and MECOM .”
BackgroundCancer gene therapy: an awkward adolescence
Gottesman, M. (2003) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7700602 · Cited by 76
Chitosan and its derivatives: vectors in gene therapy
Kritchenkov, A. S., Andranovitš, S., & Skorik, Y. (2017) · Russian Chemical Reviews · doi:10.1070/rcr4636 · Cited by 75
Almeida-Porada, G. D., Atala, A., & Porada, C. D. (2016) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2016.20 · Cited by 73
Manipulating piggyBac Transposon Chromosomal Integration Site Selection in Human Cells
Kettlun, C. S., Galvan, D. L., George, A. L., Kaja, A., & Wilson, M. H. (2011) · Molecular Therapy · doi:10.1038/mt.2011.129 · Cited by 72
Horn, P. A., Keyser, K. A., Peterson, L. J., Neff, T., Thomasson, B. M., Thompson, J., & Kiem, H. (2004) · Blood · doi:10.1182/blood-2003-07-2414 · Cited by 71
Zhang, T., Huang, B. Y., Yuan, Z., Hu, Y., Tabata, Y., & Gao, J. (2013) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2013.06.003 · Cited by 81
Clinical Applications Involving CNS Gene Transfer
Kantor, B., McCown, T., Leone, P., & Gray, S. J. (2014) · Advances in Genetics · doi:10.1016/b978-0-12-800149-3.00002-0 · Cited by 74
A method to sequence and quantify DNA integration for monitoring outcome in gene therapy
Brady, T., Roth, S. L., Malani, N., Wang, G. P., Berry, C. C., Leboulch, P., Hacein‐Bey‐Abina, S., Cavazzana, M., Papapetrou, E. P., Sadelain, M., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr140 · Cited by 73
“Human gene therapy has been carried out successfully for several diseases (1–8), but adverse events have occurred in which subjects developed leukemia associated with insertion of therapeutic vectors near proto-oncogenes (3,6,9,10).”
BackgroundSelf-citationPike‐Overzet, K., de Ridder, D., Weerkamp, F., Baert, M. R. M., Verstegen, M. M. A., Brugman, M. H., Howe, S. J., Reinders, M. J. T., Thrasher, A. J., Wagemaker, G., et al. (2007) · Leukemia · doi:10.1038/sj.leu.2404563 · Cited by 70
Exosome‐mediated small RNA delivery for gene therapy
Zhou, Y., Zhou, G., Tian, C., Jiang, W., Jin, L., Zhang, C., & Chen, X. (2016) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1363 · Cited by 103
Trobridge, G., Beard, B., Gooch, C., Wohlfahrt, M., Olsen, P., Fletcher, J., Malik, P., & Kiem, H. (2008) · Blood · doi:10.1182/blood-2007-09-115022 · Cited by 73
Morgan, R. A., WALKER, R. E., Carter, C. S., Natarajan, V., Tavel, J. A., Bechtel, C., Herpin, B., Muul, L. M., Zheng, Z., Jagannatha, S., et al. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.1065 · Cited by 72
Improved translation efficiency of therapeutic mRNA
Zarghampoor, F., Azarpira, N., Khatami, S. R., Behzad-Behbahani, A., & Foroughmand, A. M. (2019) · Gene · doi:10.1016/j.gene.2019.05.008 · Cited by 72
Therapeutic potential of retroviral RNAi vectors
Devroe, E., & Silver, P. A. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.3.319 · Cited by 67
“The excitement surrounding successful gene therapy of children with X-linked SCID (XSCID) and adenosine deaminase deficiency SCID [98,99] was recently subdued after two of the XSCID subjects developed T cell leukaemia [100].”
BackgroundStrom, T. S., Turner, S. J., Andreansky, S. S., Liu, H., Doherty, P. C., Srivastava, D. K., Cunningham, J. M., & Nienhuis, A. W. (2003) · Blood · doi:10.1182/blood-2002-11-3489 · Cited by 64
“γ-chain deficiency who had been treated three years earlier by retroviral mediated gene transfer has heightened concerns regarding the safety of gene therapy approaches.(50,51) Vector mediated insertional activation of the LMO2 gene, a known proto-oncogene(52),”
BackgroundGenetic engineering of T cells for adoptive immunotherapy
Varela‐Rohena, A., Carpenito, C., Pérez, E., Richardson, M. W., Parry, R. V., Milone, M. C., Scholler, J., Hao, X., Mexas, A. M., Carroll, R. G., et al. (2008) · Immunologic Research · doi:10.1007/s12026-008-8057-6 · Cited by 80
“This outcome was the result of vector integration-mediated upregulation of transcription of the proto-oncogene LMO-2 [80].”
BackgroundCiuffi, A., Diamond, T. L., Hwang, Y., Marshall, H. M., & Bushman, F. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.ft-232 · Cited by 71
“Such oncogene activation has now been seen during human gene therapy trials (Hacein-Bey-Abina et al. , 2003a,b).”
LMO2 at 25 years: a paradigm of chromosomal translocation proteins
Chambers, J. S., & Rabbitts, T. H. (2015) · Open Biology · doi:10.1098/rsob.150062 · Cited by 67
“Aberrant expression of LMO2, following activation by retroviral insertion, has also led to a T-ALL-like leukaemia arising in four of the children treated in X chromosomelinked severe combined immuno-deficiency syndrome (X-SCID) gene therapy trials [9,10,38].”
InfluentialViral Vector–mediated and Cell-based Therapies for Treatment of Cystic Fibrosis
Flotte, T. R., Ng, P., Dylla, D. E., McCray, P. B., Wang, G., Kolls, J. K., & Hu, J. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300002 · Cited by 66
Gene modification strategies to induce tumor immunity.
Murphy, A., Westwood, J. A., Teng, M., Moeller, M., Darcy, P., & Kershaw, M. (2005) · Immunity · doi:10.1016/j.immuni.2005.03.007 · Cited by 70
Gene Therapy for Epidermolysis Bullosa
Marinkovich, M. P., & Tang, J. Y. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.11.036 · Cited by 88
Gene therapy imaging in patients for oncological applications
Peñuelas, I., Haberkorn, U., Yaghoubi, S., & Gambhir, S. (2005) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-005-1928-3 · Cited by 69
“The induction of mutations due to integration of the transduced DNA into the host’s genome in non-target cells is another great concern [114, 115], and the better way to avoid it would be to obtain extremely specific vectors that are only able to transduce specific cells [116].”
BackgroundUse of HIV as a gene transfer vector.
Pluta, K. D., & Kacprzak, M. M. (2009) · Acta Biochimica Polonica · doi:10.18388/abp.2009_2490 · Cited by 76
“…such an adverse outcome has been reported earlier in two X-linked severe combined immunodeficiency (X-SCID1) patients treated with cytokine-activated hematopoietic stem/progenitor cells (HSPCs) transduced with murine leukemia virus — MLV (trial initiated in 1999) (Hacein-Bey-Abina et al., 2003).”
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Vogel, R., Amar, L., Thi, A. D., Saillour, P., & Mallet, J. (2004) · Human Gene Therapy · doi:10.1089/104303404772679968 · Cited by 68
Molecular approaches to diagnose Diamond-Blackfan anemia: The EuroDBA experience.
Costa, L. D. D., O'Donohue, M., van Dooijeweert, B., Albrecht, K., Unal, S., Ramenghi, U., Leblanc, T., Dianzani, I., Tamary, H., Bartels, M., et al. (2017) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2017.10.017 · Cited by 68
Lymphoid Regeneration from Gene-Corrected SCID-X1 Subject-Derived iPSCs
Menon, T., Firth, A. L., Scripture-Adams, D. D., Galić, Z., Qualls, S. J., Gilmore, W. B., Ke, E., Singer, O., Anderson, L., Bornzin, A. R., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.02.005 · Cited by 71
Bentley, D. (2004) · Nature · doi:10.1038/nature02622 · Cited by 68
“, it is proving a challenge to continue translation into clinical practic”
Bouazzaoui, A., Abdellatif, A. A. H., Al-Allaf, F. A., Bogari, N. M., Al-Dehlawi, S., & Qari, S. H. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13020140 · Cited by 92
“Therapy using retroviral vectors has been demonstrated to be an efficient treatment for different disorders, including X-linked SCID (SCID-X1), chronic granulomatous disease (CGD), and adenosine deaminase-deficient SCID [43–46].”
BackgroundDNA Nicks Promote Efficient and Safe Targeted Gene Correction
Davis, L. J., & Maizels, N. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023981 · Cited by 67
“TGC preserves regulatory sequences necessary for proper gene expression, and eliminates the danger of insertional activation of protooncogenes that can accompany integration of a therapeutic transgene carried on a viral vector [9].”
Baril, P., Martín-Duque, P., & Vassaux, G. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00412.x · Cited by 67
“However, transduction of human patients with integrative vectors has been shown to lead to adverse events, in particular leukaemia (Hacein-Bey-Abina et al., 2003).”
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Dass, B., Olanow, C. W., & Kordower, J. H. (2006) · Neurology · doi:10.1212/wnl.66.10_suppl_4.s89 · Cited by 62
RNA-based gene transfer for adult stem cells and T cells
Smits, E., Ponsaerts, P., Lenjou, M., Nijs, G., van Bockstaele, D. V., Berneman, Z., & Tendeloo, V. V. (2004) · Leukemia · doi:10.1038/sj.leu.2403463 · Cited by 67
Atkins, A., Chung, C.-H., Allen, A. G., Dampier, W., Gurrola, T. E., Sariyer, I. K., Nonnemacher, M. R., & Wigdahl, B. L. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.673022 · Cited by 78
Building a CAR-Treg: Going from the basic to the luxury model
Rosado‐Sánchez, I., & Levings, M. K. (2020) · Cellular Immunology · doi:10.1016/j.cellimm.2020.104220 · Cited by 69
Update on gene therapy for immunodeficiencies
Kohn, D. B. (2010) · Clinical Immunology · doi:10.1016/j.clim.2009.12.003 · Cited by 67
Meijering, B. D., Henning, R., van Gilst, W. V., Gavrilović, I., van Wamel, A., & Deelman, L. (2007) · Journal of drug targeting (Print) · doi:10.1080/10611860701605088 · Cited by 66
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BackgroundThakker, D. R., Hoyer, D., & Cryan, J. F. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.08.006 · Cited by 78
Adeno-Associated Virus Site-Specific Integration and AAVS1 Disruption
Hamilton, H., Gomos, J. B., Berns, K. I., & Falck-Pedersen, E. (2004) · Journal of Virology · doi:10.1128/jvi.78.15.7874-7882.2004 · Cited by 67
“Recently, random integration and subsequent activation of cellular genes have created safety concerns about retrovirus vectors (13), and recombinant AAV vectors have also been shown to disrupt cellular genes (16, 25).”
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Zhang, Y., Boado, R. J., & Pardridge, W. M. (2003) · Pharmaceutical Research · doi:10.1023/b:pham.0000003375.13655.f9 · Cited by 66
“Long-term gene expression is possible with viral vectors that permanently integrate into the host genome, but this approach is associated with the risk of insertional mutagenesis (1).”
Foamy-virus-mediated gene transfer to canine repopulating cells.
Kiem, H., Allen, J., Trobridge, G., Olson, E., Keyser, K., Peterson, L., & Russell, D. (2007) · Blood · doi:10.1182/blood-2006-04-016741 · Cited by 66
Palombarini, F., Masciarelli, S., Incocciati, A., Liccardo, F., Fabio, E. D., Iazzetti, A., Fabrizi, G., Fazi, F., Macone, A., Bonamore, A., et al. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-00921-5 · Cited by 82
Kerns, H. M. M., Ryu, B., Stirling, B., Sather, B., Astrakhan, A., Humblet-Baron, S., Liggitt, D., & Rawlings, D. (2010) · Blood · doi:10.1182/blood-2009-09-241869 · Cited by 65
“Unfortunately, RV therapy in both X-linked SCID and chronic granulomatous disease has led to unanticipated adverse events due to LTR-mediated, proto-oncogene transcriptional activation.(12,13) Thus, activating RV insertions can lead to emergence of clonal For personal use only.”
BackgroundMassively parallel pyrosequencing in HIV research
Bushman, F. D., Hoffmann, C., Ronen, K., Malani, N., Minkah, N. K., Rose, H. M., Tebas, P., & Wang, G. P. (2008) · AIDS · doi:10.1097/qad.0b013e3282fc972e · Cited by 67
“Related studies [20,21] on integration site distributions are also important in the gene therapy field, in which integration of therapeutic retroviral vectors has resulted in insertional activation of proto-oncogenes and clinical adverse events.”
BackgroundLiu, L., Liu, H.-Z., Visner, G., & Fletcher, B. (2006) · The FASEB Journal · doi:10.1096/fj.06-6254fje · Cited by 65
“Given that SB transposons integrate within the host genome, there is some concern this approach may induce tumorigenic mutations, as has been seen with retrovirus (49).”
BackgroundCationic liposome–DNA complexes: from liquid crystal science to gene delivery applications
Safinya, C., Ewert, K., Ahmad, A., Evans, H. M., Raviv, U., Needleman, D., Lin, A. J., Slack, N., George, C., & Samuel, C. (2006) · Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences · doi:10.1098/rsta.2006.1841 · Cited by 65
“…or gene regions of a host genome leading to cancer), where two out of ten children developed leukaemia in a trial to correct X-linked severe combined immunodeficiency with an engineered retrovirus vector (Cavazzana-Calvo et al. 2000; Hacein-Bey-Abina et al. 2003a,b; Williams & Baum 2003).”
BackgroundLi, Z.-X., Schwieger, M., Lange, C., Kraunus, J., Sun, H.-Y., van den Akker, E. V. D., Modlich, U., Serinsöz, E., Will, E., von Laer, D., et al. (2003) · Experimental Hematology · doi:10.1016/j.exphem.2003.08.008 · Cited by 65
“efficiency [8,9].”
Xiong, H., Liu, S., Wei, T., Cheng, Q., & Siegwart, D. J. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.06.030 · Cited by 92
Rahman, S., Magnussen, M., León, T. E., Farah, N., Li, Z., Abraham, B. J., Alapi, K. Z., Mitchell, R. J., Naughton, T., Fielding, A. K., et al. (2017) · Blood · doi:10.1182/blood-2016-09-742148 · Cited by 86
“Reported mechanisms of aberrant LMO2 expression in human T-ALL include i) recurrent chromosomal translocations, such as t(11;14)(p13;q11) and t(7;11)(q35;p13); ii) cryptic deletions of an upstream negative regulatory region, as in del(11)(p12p13); and iii) retroviral insertional mutagenesis at the LMO2 locus during ge…”
BackgroundBerger, C., Blau, C., Huang, M.-L. W., Iuliucci, J., Dalgarno, D., Gaschet, J., Heimfeld, S., Clackson, T., & Riddell, S. R. (2004) · Blood · doi:10.1182/blood-2003-08-2908 · Cited by 64
“highlighted by the recent observation of an acquired lymphoproliferative disorder in severe combined immunodeficiency (SCID) patients linked to retrovirally activated expression of a signalling protein.(58) We are continuing to characterize the properties of T cells transduced with ∆LNGFR containing constructs, includ…”
BackgroundNon-viral gene delivery with cationic liposome-DNA complexes.
Ewert, K., Ahmad, A., Bouxsein, N. F., Evans, H. M., & Safinya, C. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-237-3_10 · Cited by 64
Genome Editing B.C. (Before CRISPR): Lasting Lessons from the “Old Testament”
Urnov, F. D. (2018) · The CRISPR Journal · doi:10.1089/crispr.2018.29007.fyu · Cited by 71
“A severe adverse event then occurred in this trial: some of the subjects developed leukemia, which in some cases was fatal, due to insertional mutagenesis from the semi-randomly integrating vector.(44) This heightened interest in efficient repair of disease-causing mutations at their native location.”
Ferrer-Miralles, N., Rodríguez‐Carmona, E., Corchero, J., García-Fruitós, E., Vázquez, E., & Villaverde, A. (2015) · Critical Reviews in Biotechnology · doi:10.3109/07388551.2013.833163 · Cited by 63
LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives
Al-Allaf, F. A., Coutelle, C., Waddington, S. N., David, A. L., Harbottle, R. P., & Themis, M. (2010) · International Archives of Medicine · doi:10.1186/1755-7682-3-36 · Cited by 60
“These models have confirmed that insertion of RV, and to a lesser extent SIN-RV and LV can contribute to leukaemic development [85,201-206].”
BackgroundInfluentialPreclinical development of T cell receptor gene therapy
Bendle, G. M., Haanen, J. B. A. G., & Schumacher, T. N. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.02.007 · Cited by 48
Induction of megakaryocytes to synthesize and store a releasable pool of human factor VIII
Wilcox, D., Shi, Q., Nurden, P., Haberichter, S., Rosenberg, J., Johnson, B. D., Nurden, A., White, G. C., II, & Montgomery, R. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2003.00534.x · Cited by 63
Moreno-Carranza, B., Gentsch, M., Stein, S., Schambach, A., Santilli, G., Rudolf, E., Ryser, M., Haria, S., Thrasher, A. J., Baum, C., et al. (2008) · Gene Therapy · doi:10.1038/gt.2008.143 · Cited by 61
Dever, D. P., & Porteus, M. H. (2017) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000385 · Cited by 62
The Promise and the Hope of Gene Therapy
Papanikolaou, E., & Bosio, A. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.618346 · Cited by 101
Chimeric Receptor mRNA Transfection as a Tool to Generate Antineoplastic Lymphocytes
Rabinovich, P., Komarovskaya, M., Wrzesinski, S. H., Alderman, J. L., Budak-Alpdogan, T., Karpikov, A., Guo, H., Flavell, R., Cheung, N.-K. V., Weissman, S., et al. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.068 · Cited by 62
“However, these methods carry the risk of irreversible genomic alterations resulting from exogenous DNA integration (Hacein-Bey-Abina et al. , 2003).”
Gene therapy for the fetus: is there a future?
David, A. L., & Peebles, D. (2007) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2007.08.008 · Cited by 63
Optimising histidine rich peptides for efficient DNA delivery in the presence of serum
Mason, A. J., Leborgne, C., Moulay, G., Martinez, A., Danos, O., Bechinger, B., & Kichler, A. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.12.004 · Cited by 67
Kobayashi, N., Nishikawa, M., & Takakura, Y. (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2004.12.006 · Cited by 62
Gene therapy for optic nerve disease
Martin, K. R. G., & Quigley, H. A. (2004) · Eye · doi:10.1038/sj.eye.6701579 · Cited by 49
Synthetic biology as driver for the biologization of materials sciences
Morales, O. B., Gueye, M., Lacombe, L., Nowak, C., Schmachtenberg, R., Hörner, M., Jerez‐Longres, C., Mohsenin, H., Wagner, H. J., & Weber, W. (2021) · Materials Today Bio · doi:10.1016/j.mtbio.2021.100115 · Cited by 74
Hackett, C. S., Geurts, A. M., & Hackett, P. B. (2007) · Genome biology · doi:10.1186/gb-2007-8-s1-s12 · Cited by 63
“These adverse findings, including one death, occurred 3 years or more after administration of therapeutic murine leukemia virus (MLV)derived retrovirus vectors [25,26].”
BackgroundGene therapy: Is IL2RG oncogenic in T-cell development?
Pike-Overzet, K., de Ridder, D., Weerkamp, F., Baert, M., Verstegen, M., Brugman, M., Howe, S., Reinders, M., Thrasher, A., Wagemaker, G., et al. (2006) · Nature · doi:10.1038/nature05218 · Cited by 61
The structural and molecular biology of type III galactosemia
Timson, D. (2006) · IUBMB Life - A Journal of the International Union of Biochemistry and Molecular Biology · doi:10.1080/15216540600644846 · Cited by 61
“However, the relatively small number of patients and recent problems with gene therapy technologies ( 36 ) mean that Notes : a G, generalized; I, intermediate; P, peripheral.”
BackgroundGene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art
Amato, A., Arrigo, A., Aragona, E., Manitto, M. P., Saladino, A., Bandello, F. M., & Parodi, M. B. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.750586 · Cited by 68
“ALMS1 ALMS Protein Photoreceptor ciliary transport ∼460 (17)”
BackgroundUltrasound and microbubble-assisted gene delivery: recent advances and ongoing challenges.
Delalande, A., Postema, M., Mignet, N., Midoux, P., & Pichon, C. (2012) · Therapeutic delivery · doi:10.4155/tde.12.100 · Cited by 60
Brendel, C., Müller-Kuller, U., Schultze‐Strasser, S., Stein, S., Chen-Wichmann, L., Krattenmacher, A., Kunkel, H., Dillmann, A., Antoniou, M. N., & Grez, M. (2011) · Gene Therapy · doi:10.1038/gt.2011.167 · Cited by 62
DNA encapsulation by biocompatible catanionic vesicles.
Rosa, M., Miguel, M. D. G., & Lindman, B. (2007) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2006.07.084 · Cited by 60
Prospects for gene therapy of haemophilia
Nathwani, A. C., Davidoff, A. M., & Tuddenham, E. G. D. (2004) · Haemophilia · doi:10.1111/j.1365-2516.2004.00926.x · Cited by 57
“This was shown to be due to insertional mutagenesis [2, 3 ], which from being a theoretical risk, has now become a reality.”
BackgroundSchroers, R., Hildebrandt, Y., Hasenkamp, J., Glass, B., Lieber, A., Wulf, G., & Piesche, M. (2004) · Experimental Hematology · doi:10.1016/j.exphem.2004.03.010 · Cited by 60
Toolbox for retrovectorologists
Pagès, J., & Bru, T. (2004) · Journal of Gene Medicine · doi:10.1002/jgm.498 · Cited by 60
“However, it has recently been stopped after a ‘‘leukemialike’’ syndrome, affecting T cells, arose in two patients who received ex vivo transduced CD34+ cells [2,138].”
BackgroundDesign and potential of non-integrating lentiviral vectors
Shaw, A., & Cornetta, K. (2014) · Biomedicines · doi:10.3390/biomedicines2010014 · Cited by 60
“The phenomenon of insertional mutagenesis occurs when regulatory regions in the vector activate surrounding genes involved with cell growth or the integration disrupts genes resulting in growth dysregulation or genetic instability [9,14,15].”
BackgroundBear, A. S., Morgan, R. A., Cornetta, K., June, C. H., Binder-Scholl, G., Dudley, M. E., Feldman, S. A., Rosenberg, S. A., Shurtleff, S. A., Rooney, C. M., et al. (2012) · Molecular Therapy · doi:10.1038/mt.2011.288 · Cited by 59
Engineering strategies to safely drive CAR T-cells into the future
Rossi, M., & Breman, E. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1411393 · Cited by 68
Polymers in gene therapy technology
Hosseinkhani, H., Abedini, F., Ou, K., & Domb, A. J. (2014) · Polymers for Advanced Technologies · doi:10.1002/pat.3432 · Cited by 61
Loew, R., Meyer, Y., Kuehlcke, K., Gama-Norton, L., Wirth, D., Häuser, H., Stein, S., Grez, M., Thornhill, S. I., Thrasher, A. J., et al. (2009) · Gene Therapy · doi:10.1038/gt.2009.134 · Cited by 51
“Alternative” endocytic mechanisms exploited by pathogens: New avenues for therapeutic delivery?
Medina-Kauwe, L. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.06.009 · Cited by 59
Evolving gene therapy approaches for osteosarcoma using viral vectors: Review
Witlox, A. M. A., Lamfers, M. L. M., Wuisman, P. I. J. M., Curiel, D. T., & Siegal, G. P. (2007) · Bone · doi:10.1016/j.bone.2006.10.017 · Cited by 53
“Next to these tragic events, one of the first success of gene therapy also brought a major tragedy as was reported in 2000 when a group in Paris succeeded in totally correcting Severe Combined Immune Deficiency using a retroviral vector in children, but 2 of the treated children later developed leukemia (49).”
BackgroundCRISPR/Cas9 ribonucleoprotein-mediated genome and epigenome editing in mammalian cells
Bloomer, H., Khirallah, J., Li, Y., & Xu, Q. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114087 · Cited by 75
Metadata
- Authors
- Hacein-Bey-Abina, S., von Kalle, C., Schmidt, M., Le Deist, F., Wulffraat, N., McIntyre, E., Radford, I., Villeval, J.-L., Fraser, C. C., Cavazzana-Calvo, M., & Fischer, A.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-01-16
- Volume
- 348
- Issue
- 3
- Pages
- 255-256
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2323613689
- Cited by
- 1,867
- References
- 0
- Citations by year
- 2026: 29 · 2025: 32 · 2024: 31 · 2023: 25 · 2022: 47 · 2021: 52 · 2020: 46 · 2019: 50 · 2018: 45 · 2017: 63 · 2016: 65 · 2015: 84 · 2014: 87 · 2013: 92 · 2012: 92
- FWCI
- 86.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- DigitalGeorgetown (Georgetown University Library) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- X-linked severe combined immunodeficiency, gene therapy, adverse events, gene therapy safety
- MeSH terms
- Chromosomes, Human, Pair 11, DNA-Binding Proteins, Humans, Genetic Linkage, Metalloproteins, Proto-Oncogene Proteins, Retroviridae, Genetic Therapy, Gene Expression, Mutagenesis, Insertional, Severe Combined Immunodeficiency, Lymphocyte Count, Chromosomes, Human, X, Adaptor Proteins, Signal Transducing, Precursor Cell Lymphoblastic Leukemia-Lymphoma, LIM Domain Proteins
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