The DOI matches its Crossref record.
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 . . .
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
No references could be resolved yet.
Cited by
Sorted by citations
Items 901–1,000 of 1,003
In vitro adenovirus mediated gene transfer to the human cornea
Jessup, C., Brereton, H., Coster, D. J., & Williams, K. (2005) · British Journal of Ophthalmology · doi:10.1136/bjo.2004.061754 · Cited by 17
Identification of Synthetic Endothelial Cell-Specific Promoters by Use of a High-Throughput Screen
Dai, C., McAninch, R., & Sutton, R. (2004) · Journal of Virology · doi:10.1128/jvi.78.12.6209-6221.2004 · Cited by 17
“Such nonregulated promoters can cause difficulties, highlighted by the recent experience in the SCID-X1 patients who received ex vivo retrovirally transduced hematopoietic stem cells and later developed acute lymphoblastic leukemia (11), presumably due to oncogenic activation of the LMO-2 gene by the intact murine leu…”
BackgroundCurrent perceptions of cardiovascular gene therapy.
Dzau, V., Beatt, K., Pompilio, G., & Smith, K. M. (2003) · American Journal of Cardiology · doi:10.1016/s0002-9149(03)00964-0 · Cited by 17
Cell therapy: leveraging nature's therapeutic potential.
Humes, H. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000082692.79381.96 · Cited by 17
“This approach is more controllable than indiscriminate direct injections of genes or gene vectors into the patient, with the inability to control the final destination of the gene in the body or to retrieve the gene and the genetically modified cells from the body if unwanted events arise (10,11).”
BackgroundClinical Gene Therapy Research Utilizing Ribozymes
Ngok, F. K., Mitsuyasu, R., Macpherson, J., Boyd, M. P., Symonds, G. P., & Amado, R. (2004) · Humana Press eBooks · doi:10.1385/1-59259-746-7:581 · Cited by 17
Scobie, L., Hector, R. D., Grant, L., Bell, M., Nielsen, A. A., Meikle, S., Philbey, A., Thrasher, A. J., Cameron, E. R., Blyth, K., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.59 · Cited by 29
Advancements in Hematopoietic Stem Cell Gene Therapy: A Journey of Progress for Viral Transduction
Giommetti, A., & Papanikolaou, E. (2024) · Cells · doi:10.3390/cells13121039 · Cited by 17
State of Gene Therapy for Monogenic Cardiovascular Diseases
Bains, S., Giudicessi, J. R., Odening, K. E., & Ackerman, M. J. (2024) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2023.11.003 · Cited by 16
Viral Vectors in Gene Replacement Therapy
Minskaia, E., Galieva, A., Egorov, A. D., Ivanov, R. A., & Karabelsky, A. V. (2023) · Biochemistry (Moscow) · doi:10.1134/s0006297923120179 · Cited by 19
Bateman-House, A., Shah, L., Escandon, R., McFadyen, A., & Hunt, C. (2022) · Pharmaceutical Medicine · doi:10.1007/s40290-022-00451-x · Cited by 16
Fernández-Frías, I., Pérez-Luz, S., & Díaz-Nido, J. (2020) · Molecular Therapy: Methods & Clinical Development · doi:10.1016/j.omtm.2020.03.005 · Cited by 16
“An ideal gene therapy protocol consists of single-administration of the therapeutic gene, which subsequently persists and segregates alongside chromosomes, maintained in episomes to avoid risk of insertional mutagenesis.(3,4) One of the main challenges from the beginning of gene therapy research was targeting genes of…”
BackgroundChung, H., Chen, X., Yu, Y., Lee, H., Song, C. H., Choe, H., Lee, S., Kim, H., & Hong, S. (2017) · FEBS Open Bio · doi:10.1002/2211-5463.12357 · Cited by 17
Everson, E. M., Olzsko, M. E., Leap, D. J., Hocum, J. D., & Trobridge, G. D. (2016) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2016.48 · Cited by 20
Gene therapy's out-of-body experience
Scott, C. T., & DeFrancesco, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3592 · Cited by 14
Megakaryocyte- and megakaryocyte precursor–related gene therapies
Wilcox, D. A. (2016) · Blood · doi:10.1182/blood-2015-07-607937 · Cited by 20
“X-SCID may be particularly susceptible to leukemogenesis because correction of the g (c) gene defect confers a survival advantage to the transduced cells; this, plus alterations in genes such as LMO-2 that control cell division, may result in uncontrolled growth of cells that have a survival advantage.(85,86) Another…”
BackgroundNasimuzzaman, M., Kim, Y., Wang, Y., & Persons, D. A. (2014) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2014.20 · Cited by 16
Daniel‐Meshulam, I., Yaakobi, S., Ankri, C., & Cohen, C. J. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00186 · Cited by 14
Gene therapy of inherited immunodeficiencies
Santilli, G., Thornhill, S. I., Kinnon, C., & Thrasher, A. J. (2008) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.8.4.397 · Cited by 28
“Four patients in the French clinical trial for SCID-X1 have developed lymphoproliferative diseases as a result of insertional mutagenesis and aberrant expression of adjacent proto-oncogenes [66] .”
BackgroundThe Harm-Benefit Tradeoff in “Bad Deal” Trials
Nycum, G., & Reid, L. (2008) · Kennedy Institute of Ethics Journal · doi:10.1353/ken.2008.0004 · Cited by 16
“7 In another research program, three trial participants with severe X-linked severe combined immunodeficiency (SCID) disease developed leukemia, likely as a result of the combined action of the transgene and of the viral vector used to introduce the transgene (Check 2002, 2005; Hacein-Bey-Albina et al. 2003).”
BackgroundHigh-level secretion of growth hormone by retrovirally transduced primary human keratinocytes
Peroni, C. N., Cecchi, C. R., Damiani, R., Soares, C. R., Ribela, M., Arkaten, R., & Bartolini, P. (2006) · Molecular Biotechnology · doi:10.1385/mb:34:2:239 · Cited by 16
“The initial excitement became a serious concern when a leukemia-like condition was developed in 2/11 children treated in France because of integration of the retrovirus vector near the LMO2 proto-oncogene promoter ( 9 ,10).”
BackgroundCombining cell therapy and nanotechnology
Halberstadt, C. R., Emerich, D. F., & Gonsalves, K. (2006) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.6.10.971 · Cited by 13
“Calcium ionophores have very low transfection rates and the viral vectors used so far have issues, including shedding of viral proteins, that may lead to an intensive immune response (which has led to one reported death [61,62] and the development of cancer [2,63,64]).”
BackgroundWong, A. (2006) · The National Catholic Bioethics Quarterly · doi:10.5840/ncbq20066331 · Cited by 16
Gene therapy for spinal fusion.
Phillips, F., Bolt, P. M., He, T.-C., & Haydon, R. (2005) · The spine journal · doi:10.1016/j.spinee.2005.02.015 · Cited by 16
Therapeutic Angiogenesis for Treatment of Peripheral Vascular Disease
Idris, N. M., Haider, H. K., Goh, M. W. K., & Sim, E. K. W. (2004) · Growth Factors · doi:10.1080/08977190412331284344 · Cited by 18
“The deleterious effect of retroviral transduction is also highlighted in a recent report that showed retrovirally transduced human cells have the potential of causing malignant transformation (Hacein-Bey-Abina et al., 2003).”
BackgroundLambert, M., Leijonhufvud, C., Segerberg, F., Melenhorst, J. J., & Carlsten, M. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0338-3_18 · Cited by 19
de Ravin, S. D., & Malech, H. (2009) · Immunologic research · doi:10.1007/s12026-008-8073-6 · Cited by 16
“In 4 out of 9 patients from the first study, insertion of the gene therapy vector resulted in upregulation of host cellular oncogenes and consequent leukemogenesis within 3–6 years of gene therapy [77–79].”
BackgroundYang, Y., Miao, Z., Zhang, H.-J., Wang, Y., Gao, J., & Feng, M. (2006) · Differentiation · doi:10.1111/j.1432-0436.2006.00111.x · Cited by 15
Induction of T cell immunity by cutaneous genetic immunization with recombinant lentivector
He, Y., & Falo, L. D. (2006) · Immunologic Research · doi:10.1385/ir:36:1:101 · Cited by 14
“com web-site], somewhat alleviating concerns of insertional mutagenisis raised by studies utilizing integration-capable oncoretroviral vectors (34,35).”
BackgroundIs retroviral gene marking too dangerous to use?
Brenner, M., & Heslop, H. (2003) · Cytotherapy · doi:10.1080/14653240310001307 · Cited by 16
Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.
Metovic, J., Li, Y., Gong, Y., & Eichler, F. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00443 · Cited by 16
Albalawi, Y. A. (2025) · Medical Oncology · doi:10.1007/s12032-025-02928-6 · Cited by 16
“Similarly, the random integration of retrovirus in the host genome of patients receiving CAR-T cells has been observed [23, 24].”
Accelerating Diverse Cell-Based Therapies Through Scalable Design
Peterman, E. L., Ploessl, D. S., & Galloway, K. E. (2024) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-100722-121610 · Cited by 17
“Although enhanced screening of engineered cells may mitigate these dangers, reports of oncogenesis in γ -retroviral human gene therapy trials have led to strict safety regulations for retrovirally engineered cell products (94–96).”
piggyBac-transposon-mediated CAR-T cells for the treatment of hematological and solid malignancies
Yagyu, S., & Nakazawa, Y. (2023) · International Journal of Clinical Oncology · doi:10.1007/s10147-023-02319-9 · Cited by 15
“In a report on genetically engineered hematopoietic stem cell therapy that used RV to treat primary immunodeficiency, one patient developed acute leukemia derived from genetically engineered T cells due to oncogenic activation by the transgene [1, 2].”
BackgroundLi, L., Mitra, A., Cui, K., Zhao, B., Choi, S., Lee, J. Y., Stamos, D. B., El‐Khoury, D., Warzecha, C. C., Pfeifer, K. E., et al. (2020) · Blood · doi:10.1182/blood.2019000794 · Cited by 16
A Practical Guide to Genome Editing Using Targeted Nuclease Technologies
Porter, S. N., Levine, R. M., & Pruett‐Miller, S. M. (2019) · Comprehensive physiology · doi:10.1002/cphy.c180022 · Cited by 18
“A previously reported adverse effect of non-nuclease-based gene therapy has been oncogenic off-target mutagenesis (see section A genome editing cautionary tale for details) (136).”
Now Is the Time to Use Molecular Gene Testing for the Diagnosis of Primary Immune Deficiencies
Heimall, J. R. (2019) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2018.12.022 · Cited by 15
Browning, D. L., Collins, C. P., Hocum, J. D., Leap, D. J., Rae, D. T., & Trobridge, G. D. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.110 · Cited by 13
“Early SCID-X1 (X-linked severe combined immunodeficiency) clinical trials using gammaretroviral (GV) vectors were successful in treating the SCID-X1 phenotype; however, patients in two clinical trials developed leukemia as a result of vector-induced genotoxicity.(7,8) Preclinical studies and additional clinical trials…”
BackgroundConcise Review: Patient-Derived Stem Cell Research for Monogenic Disorders
Qin, Y., & Gao, W. (2015) · Stem Cells · doi:10.1002/stem.2112 · Cited by 17
Yang, G.-H., Kramer, M., Fernández-Ruiz, V., Kawa, M., Huang, X., Liu, Z., Prieto, J., & Qian, C. (2015) · Scientific Reports · doi:10.1038/srep17166 · Cited by 15
Beyond branching: multiknot structured polymer for gene delivery.
Aied, A., Zheng, Y., Newland, B., & Wang, W.-X. (2014) · Biomacromolecules · doi:10.1021/bm5013162 · Cited by 15
Progress and prospects for engineered T cell therapies
Qasim, W., & Thrasher, A. J. (2014) · British Journal of Haematology · doi:10.1111/bjh.12981 · Cited by 16
“In severe combined immunodeficiency (SCIDX1) (Hacein-Bey-Abina et al, 2003, 2008; Howe et al, 2008), Wiskott-Aldrich Syn- drome (Braun et al, 2014), and Chronic Granulomatous dis- ease (Ott et al, 2006); a number of subjects subsequently developed T cell or myeloid leukaemias.”
BackgroundParkinson disease: Gene therapy for Parkinson disease—a hope, or a dream?
Olanow, C. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.45 · Cited by 15
Uchida, N., Weitzel, R. P., Evans, M., Green, R., Bonifacino, A. C., Krouse, A. E., Metzger, M. E., Hsieh, M. M., Donahue, R. E., & Tisdale, J. F. (2013) · Gene Therapy · doi:10.1038/gt.2013.67 · Cited by 15
Myocardial Repair and Regeneration: Bone Marrow or Cardiac Stem Cells?
Oldroyd, K. G., Berry, C., & Bartúnek, J. (2012) · Molecular Therapy · doi:10.1038/mt.2012.99 · Cited by 15
Balaggan, K. S., Durán, Y., Georgiadis, A., Thaung, C., Barker, S. E., Buch, P. K., MacNeil, A., Robbie, S. J., Bainbridge, J. W., Smith, A. J., et al. (2011) · Gene Therapy · doi:10.1038/gt.2011.194 · Cited by 15
Potential of nucleofected human MSCs for insulin secretion
Kim, J. H., Shin, K., Li, T.-Z., & Suh, H. (2011) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.371 · Cited by 15
ΦC31 integrase interacts with TTRAP and inhibits NFκB activation
Wang, B.-Y., Xu, G.-L., Zhou, C.-H., Tian, L., Xue, J.-L., Chen, J.-Z., & Jia, W. (2010) · Molecular Biology Reports · doi:10.1007/s11033-009-9829-3 · Cited by 15
“Safety concerns related to retrovirus-mediated gene therapy have been heightened by clinical incidences of insertional mutagenesis [ 1 ].”
BackgroundTransKingdom RNA interference: a bacterial approach to challenges in RNAi therapy and delivery
Keates, A. C., Fruehauf, J. H., Xiang, S., & Li, C. J. (2008) · Biotechnology and Genetic Engineering Reviews · doi:10.5661/bger-25-113 · Cited by 11
“However, for use as a vehicle for RNAi-based therapy in humans, viral delivery still faces safety concerns related to serious adverse events observed with viral vectors in the context of gene therapy trials (Hacein-Bey-Abina et al., 2003).”
BackgroundGenomic Context Vectors and Artificial Chromosomes for Cystic Fibrosis Gene Therapy
Conese, M., Boyd, A., Gioia, S. D., Auriche, C., & Ascenzioni, F. (2007) · Current Gene Therapy · doi:10.2174/156652307780859026 · Cited by 11
“Finally, insertional mutagenesis is still a major concern, as for oncoretroviral vectors [Hacein-Bey-Abina et al. 2003a; Hacein-BeyAbina et al. 2003b; Fischer et al. 2004; Fischer and Cavazzano-Calvo 2005].”
BackgroundRole of Integrin Cross-Regulation in Parvovirus B19 Targeting
Weigel-Kelley, K. A., Yoder, M., Chen, L.-Y., & Srivastava, A. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.909 · Cited by 15
Gene therapy for transplantation with viral vectors – how much of the promise has been realised?
Tan, P. H., Tan, P. L., George, A. J., & Chan, C. (2006) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.6.8.759 · Cited by 15
“For example, three children developed a leukaemia-like disease after receiving gene therapy [2,89].”
BackgroundGene therapy for treatment of inherited haematological disorders
Herzog, R. W., Cao, O., Hagstrom, J. N., & Wang, L. (2006) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.6.5.509 · Cited by 13
“This strategy led to successful treatment of two forms of SCID [2,3], although occurrence of leukaemia in therapy for one form of this disease illustrated the need to modify the protocol in order to minimise risks arising from insertional mutagenesis, and also pointed out the necessity to evaluate risks and benefits f…”
BackgroundMethodGene therapy for immune disorders: good news tempered by bad news.
Puck, J., & Malech, H. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.01.041 · Cited by 15
Perspectives of gene therapy for primary immunodeficiencies
Chinen, J., & Puck, J. (2004) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/00130832-200412000-00008 · Cited by 15
Evaluation of Peptide-Mediated Transduction in Human CD34+ Cells
Shen, H.-M., Mai, J. C., Qiu, L., Cao, S., Robbins, P., & Cheng, T. (2004) · Human Gene Therapy · doi:10.1089/104303404322959560 · Cited by 15
“However, the clinical use of direct genetic alteration of host genomes by retrovirus-mediated integration has been hampered by the risk of oncogenic transformation (Hacein-Bey-Abina et al., 2003).”
Gene therapy for adenosine deaminase deficiency
Aiuti, A., Ficara, F., Cattaneo, F., Bordignon, C., & Roncarolo, M. (2003) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/00130832-200312000-00007 · Cited by 15
Cell-based therapies for birth defects: a role for adult stem cell plasticity?
Fang, T.-C., & Poulsom, R. (2003) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.10019 · Cited by 15
Chitosan for DNA and gene therapy
Layek, B., & Singh, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-08-100228-5.00008-0 · Cited by 31
von Laer, D., Baum, C., & Protzer, U. (2009) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-540-79086-0_10 · Cited by 15
Wilson, C., & Cichutek, K. (2009) · Methods in molecular biology · doi:10.1007/978-1-59745-409-4_32 · Cited by 15
T-cell receptor gene transfer for treatment of leukemia.
Heemskerk, M., Griffioen, M., & Falkenburg, J. (2008) · Cytotherapy · doi:10.1080/14653240701883087 · Cited by 15
Gene therapy in cutaneous wound healing
Hirsch, T. (2006) · Frontiers in bioscience · doi:10.2741/2251 · Cited by 15
An organ-conformal, kirigami-structured bioelectronic patch for precise intracellular delivery
Wang, Y., Du, L., Wu, H., Li, H., Liu, J., Hu, Y., Jiang, X., Yin, D., Hao, Y., Xiao, A., et al. (2026) · Cell · doi:10.1016/j.cell.2025.12.021 · Cited by 13
Persistent hematopoietic polyclonality after lentivirus-mediated gene therapy for Fabry disease
Saleh, A. H., Rothe, M., Barber, D. L., McKillop, W. M., Fraser, G. A. M., Morel, C. F., Schambach, A., Auray‐Blais, C., West, M. L., Khan, A., et al. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.01.003 · Cited by 18
“Vector insertions near LMO2 were also associated with leukemogenesis in two other trials of gene therapy for SCID-X1.(6,7) Genomic instability and clonal progression toward myelodysplasia were reported in a retroviral-mediated gene therapy trial for X-linked chronic granulomatous disease that resulted in insertional a…”
BackgroundXiu, K., Saunders, L., Wen, L., Ruan, J., Dong, R., Song, J. W., Yang, D., Zhang, J., Xu, J., Chen, Y. E., et al. (2022) · Cells · doi:10.3390/cells12010156 · Cited by 19
“There have been resultant cases of cancer and death in ongoing clinical trials [17,18], highlighting the safety concerns associated with viral vectors, and prompting an increased interest in the development and utilization of non-viral delivery systems.”
BackgroundNanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review
Bertozzi, S., Corradetti, B., Seriau, L., Nanez, J. A. D., Cedolini, C., Fruscalzo, A., Cesselli, D., Cagnacci, A., & Londero, A. P. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12081324 · Cited by 18
Gene Editing for Inherited Red Blood Cell Diseases
Bustamante, O. Q., Fañanas-Baquero, S., Dessy-Rodríguez, M., Ojeda-Pérez, I., & Segovia, J. C. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.848261 · Cited by 20
Sowa, Y., Kishida, T., Louis, F., Sawai, S., Seki, M., Numajiri, T., Takahashi, K. A., & Mazda, O. (2021) · Cells · doi:10.3390/cells10030605 · Cited by 14
“Genetically modified cells could potentially form a tumor after transplantation, because endogenous oncogenes could be activated by the vector sequence integrated into the chromosome [21].”
BackgroundMorgan, R. A., Ma, F., Unti, M. J., Brown, D., Ayoub, P. G., Tam, C., Lathrop, L. E., Aleshe, B., Kurita, R., Nakamura, Y., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.04.006 · Cited by 19
Curative approaches for sickle cell disease: A review of allogeneic and autologous strategies
Bauer, D. E., Brendel, C., & Fitzhugh, C. D. (2017) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2017.08.014 · Cited by 15
Ruggero, K., Al‐Assar, O., Chambers, J. S., Codrington, R., Brend, T., & Rabbitts, T. H. (2016) · Leukemia · doi:10.1038/leu.2016.116 · Cited by 13
EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer
Bhavsar, D., Subramanian, K., Sethuraman, S., & Krishnan, U. (2016) · Drug Delivery · doi:10.3109/10717544.2014.973082 · Cited by 14
“Clinical trials conducted for the treatment of X-linked severe combined immune deficiency using retrovirus vectors revealed that the patients exhibited increased T-cell count because of the integration of viral genome at the first intron of LMO-2 (Hacein-Bey-Abina et al., 2003).”
BackgroundCastle, J., Kent, K. P., Fan, Y., Wallace, K., Davis, C. L., Roberts, J., Marino, M. E., Thomenius, K., Lim, H. W., Coles, E., et al. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.04.817 · Cited by 14
De novo formed satellite DNA-based mammalian artificial chromosomes and their possible applications
Katona, R. (2015) · Chromosome Research · doi:10.1007/s10577-014-9458-0 · Cited by 14
“MACs are prospectively safer alternatives to viral gene therapy vectors, which have been shown to produce insertional oncogenesis (Cavazzana-Calvo et al. 2003; Morillon et al. 2003), be associated with chromosomal deletions/rearrangements (Miller et al. 2002; Miller et al. 2004), induce systemic…”
BackgroundsiRNA: novel therapeutics from functional genomics
Joshi, B. H., & Pachchigar, K. P. (2014) · Biotechnology and Genetic Engineering Reviews · doi:10.1080/02648725.2014.921495 · Cited by 14
“However, a shortcoming for their potential for employing in clinical use is that retrovirus insert into most genome with poor control of insertion site, which can trigger oncogenic transformation such as in the SCID clinical trials (Hacein-Bey-Abina et al., 2003).”
BackgroundTarantal, A. F., & Skarlatos, S. I. (2012) · Human Gene Therapy · doi:10.1089/hum.2012.178 · Cited by 16
“…of clinical trials, to date, have not resulted in adverse findings, setbacks have occurred (Ott et al ., 2006), and it has been observed that integration of retroviral vectors near proto-oncogenes can lead to clonal dominance and leukemia (Hacein-Bey-Abina et al ., 2003; Hawkins et al ., 2011).”
Gene therapy: therapeutic applications and relevance to pathology
Both, G. W., Alexander, I. E., Fletcher, S., Nicolson, T. J., Rasko, J. E. J., Wilton, S. D., & Symonds, G. P. (2011) · Pathology · doi:10.1097/pat.0b013e32834b1dad · Cited by 15
Gene therapy for chronic neuropathic pain: how does it work and where do we stand today?
Kumar, S., Ruchi, R., James, S. R., & Chidiac, E. (2011) · Pain medicine (Malden, Mass.) · doi:10.1111/j.1526-4637.2011.01120.x · Cited by 14
Correction of SCID-X1 Using an Enhancerless Vav Promoter
Almarza, E., Zhang, F., Santilli, G., Blundell, M. P., Howe, S. J., Thornhill, S. I., Bueren, J. A., & Thrasher, A. J. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.119 · Cited by 13
“It is now understood that a major contribution to these effects arises from the use of potent regulatory sequences in these LTR-intact gammare-troviral vectors (Hacein-Bey-Abina et al ., 2003; Howe et al ., 2008).”
InfluentialChromosomal tethering and proviral integration
Delelis, O., Zamborlini, A., Thierry, S., & Saı̈b, A. (2009) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2009.08.005 · Cited by 14
Gene Repair: Pointing the finger at genetic disease
Cathomen, T., & Weitzman, M. (2005) · Gene Therapy · doi:10.1038/sj.gt.3302572 · Cited by 14
T cell suicide gene therapy to aid haematopoietic stem cell transplantation.
Qasim, W., Gaspar, H. B., & Thrasher, A. (2005) · Current Gene Therapy · doi:10.2174/1566523052997497 · Cited by 14
Sequence-specific modification of mouse genomic DNA mediated by gene targeting techniques
Sangiuolo, F., & Novelli, G. (2004) · Cytogenetic and Genome Research · doi:10.1159/000078216 · Cited by 14
Gaucher and Fabry diseases: from understanding pathophysiology to rational therapies
Brady, R. (2003) · Acta paediatrica · doi:10.1111/j.1651-2227.2003.tb00215.x · Cited by 14
“more effective transduction of patients’ stem and progenitor cells selective enrichment of transduced cells before their introduction into patients development of procedure(s) for the delivery and implantation of the transduced cells into patients’ bone marrow elimination of potentially harmful effects of retroviruses…”
BackgroundIntegrase Defective, Nonintegrating Lentiviral Vectors
Michelini, Z., Negri, D. R. M., & Cara, A. (2009) · Methods in molecular biology · doi:10.1007/978-1-60761-533-0_6 · Cited by 16
Dunbar, C. (2007) · Hematology. American Society of Hematology. Education Program · doi:10.1182/asheducation-2007.1.460 · Cited by 14
“However, in 2003 the first serious adverse event linked to genetic modification of HSCs or primitive precursor cells with integrating retrovirus vectors was reported.(5,6) This review will summarize the encouraging results of these clinical trials, explain what is known regarding the adverse events linked to genotoxic…”
BackgroundCRISPR medicine for blood disorders: Progress and challenges in delivery
Gol, T. M., Ureña-Bailén, G., Hou, Y., Sinn, R., Antony, J. S., Handgretinger, R., & Mezger, M. (2023) · Frontiers in Genome Editing · doi:10.3389/fgeed.2022.1037290 · Cited by 16
Review of Treatment for Adenosine Deaminase Deficiency (ADA) Severe Combined Immunodeficiency (SCID)
Secord, E., & Hartog, N. (2022) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s350762 · Cited by 13
“ADA deficiency was described in 1972 by Eloise Gilbert when she discovered that the red blood cells (RBC) of two patients with CID contained no ADA enzyme on gel electrophoresis.7 In initial studies looking toward possible treatments the addition of normal red blood cells to cultures of cells from ADA deficient patien…”
BackgroundInfluentialViral gene therapy for paediatric neurological diseases: progress to clinical reality
Privolizzi, R., Chu, W. S., Tijani, M., & Ng, J. (2021) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14885 · Cited by 21
“The second was gamma retroviral correction of X-linked severe combined immunodeficiency, which reconstituted immunity but vector-related leukaemia consequently developed.(5) These highlighted an inadequate understanding of vector properties, and gene therapists have worked tirelessly to engineer recombinant viral vect…”
BackgroundEffect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency
Badazhkova, V. D., Raik, S., Polyakov, D., Poshina, D., & Skorik, Y. (2020) · Polymers · doi:10.3390/polym12051057 · Cited by 13
“Viral vectors show high transfection efficiency, but they have some significant shortcomings, including immunogenicity [3,4], insertional mutagenesis [5], and low gene transfer capacity [6,7].”
BackgroundSynthesis of amphoteric curdlan derivatives for delivery of therapeutic nucleic acids.
Tong, Y., Ganbold, T., & Baigude, H. (2017) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2017.08.037 · Cited by 13
Moscatelli, I., Löfvall, H., Thudium, C. S., Rothe, M., Montano, C., Kertész, Z., Sirin, M., Schulz, A., Schambach, A., Henriksen, K., et al. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.053 · Cited by 15
“12 Instead of employing strong viral promoter/enhancer sequences, having led to severe adverse events in past gene therapy trials, 13,14 the use of weaker cellular promoters can increase treatment safety.”
Nordin, F., Ahmad, R. N. R., & Farzaneh, F. (2017) · Virus Research · doi:10.1016/j.virusres.2017.04.007 · Cited by 17
Kerr, A., Tam, L., Hale, A. B., Cioroch, M., Douglas, G., Channon, K., & Wade-Martins, R. (2016) · Molecular Therapy: Nucleic Acids · doi:10.1038/mtna.2016.86 · Cited by 13
Treating hemoglobinopathies using gene-correction approaches: promises and challenges
Cottle, R. N., Lee, C. M., & Bao, G. (2016) · Human Genetics · doi:10.1007/s00439-016-1696-0 · Cited by 17
“The advantage of the nuclease-based approach over conventional gene therapy is the elimination of risks of insertional mutagenesis or viral-induced immune response (Cavazzana-Calvo et al. 2000; Hacein-Bey-Abina et al. 2003b).”
BackgroundNasimuzzaman, M., Lynn, D., Ernst, R., Beuerlein, M., Smith, R. H., Shrestha, A., Cross, S. J., Link, K. A., Lutzko, C., Nordling, D., et al. (2016) · Molecular Therapy: Methods & Clinical Development · doi:10.1038/mtm.2016.4 · Cited by 13
Barbero, N., Magistris, C., Quagliotto, P., Bonandini, L., Barolo, C., Buscaino, R., Compari, C., Contardi, L., Fisicaro, E., & Viscardi, G. (2015) · ChemPlusChem · doi:10.1002/cplu.201500007 · Cited by 13
Giordano, F., Appelt, J., Link, B., Gerdes, S., Lehrer, C.-I., Scholz, S. J., Paruzynski, A., Roeder, I., Wenz, F., Glimm, H., et al. (2015) · Molecular Therapy: Methods & Clinical Development · doi:10.1038/mtm.2014.61 · Cited by 13
Self-citationSchott, J. W., Hoffmann, D., Maetzig, T., Müller, F.-J., Steinemann, D., Zychlinski, D., Cantz, T., Baum, C., & Schambach, A. (2014) · Gene Therapy · doi:10.1038/gt.2014.69 · Cited by 12
McAllister, R. G., Liu, J., Woods, M. W., Tom, S. K., Rupar, C. A., & Barr, S. D. (2014) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2014.39 · Cited by 15
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
