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Virus treatment questioned after gene therapy death
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“Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo, their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications.”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [69]
In the citing paper
“Zuris et al. injected Cas9:sgRNA complexes targeting GFP gene into the cochlea of transgenic Atoh1-GFP mice. This system resulted in ~20% Cas9-mediated genome modification in hair cells [69].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [69]
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Items 501–577 of 577
Myocardial-specific gene delivery
Franz, W.-M., Müller, O. J., Katus, H. A., et al. (2000) · Steinkopff eBooks · doi:10.1007/978-3-642-57710-9_11 · Cited by 1
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Stellenwert der Gentherapie in der kardiovaskulären Medizin
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“Im Zusammenhang mit Adenovirusvektoren können schwere Nebenwirkungen und sogar Todesfälle auftreten [23].”
BackgroundGene Editing and Gene Therapy: Entering Uncharted Territory in Veterinary OncologyPreprint
Wierson, W. A., Abel, A. M., Siegler, E. L., Ekker, S. C., Johannes, C. M., Kenderian, S. S., & Mochel, J. P. (2021) · Preprints.org · doi:10.20944/preprints202105.0376.v1
“…perspective, viral vectors can be highly immunogenic and lead to adverse inflammatory reactions in patients such that, in 1999, the first gene therapyrelated fatality was reported in a clinical trial due to an inflammatory reaction in response to an adenovirus (AdV) vector (Lehrman, 1999).”
BackgroundSteps in a Translational Cancer Gene Therapy Trial
von Holzen, U. W., & Swisher, S. G. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-222-9_25 · Cited by 1
Rationally Designed Synthetic Vectors for Gene Delivery
Rao, G., Yadava, P., & Hughes, J. (2007) · The Open Drug Delivery Journal · doi:10.2174/187412660701017066 · Cited by 1
Molecular therapeutics in hematology: gene therapy
McKillop, W. M., & Medin, J. A. (2024) · doi:10.1002/9781394180486.ch22 · Cited by 1
Scott, K. J., West, E. J., Brownlie, R. J., et al. (2024) · medRxiv · doi:10.1101/2024.09.26.24314049 · Cited by 1
New Technologies in Cardiovascular Research: Gene Therapy
Hedman, M., Turunen, M. P., & Ylä‐Herttuala, S. (2006) · Springer eBooks · doi:10.1007/0-387-23329-6_5 · Cited by 1
Paavonen, K. (2003) · Työväentutkimus Vuosikirja · Cited by 1
Cellular receptors for species B adenoviruses
Marttila, M. (2007) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Sarkar, N. (2004) · Figshare
Novel Alternatives to Chemotherapy in Advanced Disease: Gene Transfer
Ghaneh, P., Halloran, C. M., Costello, E., & Neoptolemos, J. P. (2004) · Springer eBooks · doi:10.1007/978-1-85233-904-3_9
Gene Therapy Targets and the Role of Pharmacogenomics in Heart Failure
Lykouras, D., Flordellis, C. S., & Dougenis, D. (2011) · InTech eBooks · doi:10.5772/20004
Self-assembled pentablock copolymers for selective and sustained gene delivery
Zhang, B., & USDOE Office of Science (SC) (2011) · OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) · doi:10.2172/1029551
Emerging Therapies for Heart Failure
Greenberg, B., & Cleland, J. G. F. (2010) · Wiley eBooks · doi:10.1002/9780470669402.ch7
Molecular Genetics of Choroideremia
Freund, P. R., & MacDonald, I. M. (2012) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0024310
Silva, M. L. (2008) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.42.2008.tde-03062008-190643
Gene Therapy: Cure or Poison? The Proper Role of the FDA in the Bubble Boy Disease Question
Woodruff, M. R. (2004) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
A non-invasive QPCR method monitoring DNA based therapy of bladder cancer patients
Ayesh, S. K., Abu-lail, R., & HOCHBERG, A. (2006) · Vaccine · doi:10.1016/j.vaccine.2006.02.015
Special Feature Opinion Paper on the Current Status of the Regulation of Gene Therapy in Europe
Cohen‐Haguenauer, O., Rosenthal, F. M., Nsbacher, B. G., et al. (2002)
Therapeutic Innovations in Oncology
Jenkins, C., & Demetri, G. D. (2016) · doi:10.14524/cr-15-0043
Treating Hemophilia by Gene Therapy
Porada, C. D., Ignacio, G., Atala, A., & Almeida-Porada, G. D. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800548-4.00012-7
Ultrasound-based and Non-viral Technologies in Gene Therapy
Su, C., Yeh, H., Hou, C. J., Cheu, Y.-S., & Tsai, C. (2007) · 內科學誌 · doi:10.6314/jimt.2007.18(4).01
Bioluminescence Imaging of Luciferase Transgenes in Tumor Metastases Models
München, L.-M.-U., & Pharmazeutische, L. F. (2011)
Kardiovaskuläre Gentherapie - was kann der Chirurg derzeit davon erwarten?
Bonatti, J. O., Bernecker, O. Y., Chevtchik, O., Hammerer‐Lercher, A., Laufer, G., Oberhuber, A., Ott, H., Podesser, B. K., Ruttmann, E., Schachner, T., et al. (2002) · Journal für Kardiologie (Krause & Pachernegg GmbH)
Engineering delivery and release of protein therapeutics for mammalian systems
Fluri, D. A. (2008) · Repository for Publications and Research Data (ETH Zurich) · doi:10.3929/ethz-a-005708602
Abnormalities of Hepatic Protein Metabolism
A‐Kader, H. H., & Ghishan, F. K. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4377-0774-8.10072-7
Basic Electrophysiological Procedures for the Clinician
Park, D. S., & Fishman, G. I. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-0285-9.00001-6
Non-viral gene delivery and bone marrow cells in inner ear repair
Tan, B. T. G. (2008) · doi:10.32657/10356/14957
Stand der Gentherapie und der lokalen Medikamentenapplikation im kardiovaskulären Bereich
Nikol, S., & Engelmann, M. G. (2002) · Springer eBooks · doi:10.1007/978-3-642-56302-7_5
Multifunctional nanomaterials for cancer theranostics applications
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Quenneville, S. (2007) · Corpus Université Laval (Université Laval)
Design of polymeric vectors for genetic manipulation
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Early Development of the Icon Molecule for Gene Therapy of Cancer and Macular Degeneration
Garen, A. (2019) · American Journal of Biomedical Science & Research · doi:10.34297/ajbsr.2019.06.000992
Gene therapy of malignant glioma : alternative strategies and combination therapies
Stedt, H. (2015) · UEF eRepo (University of Eastern Finland)
Development of enzyme replacement therapy using liver organoids derived from human iPS cells
Ueno, Y., & Taniguchi, H. (2020) · Drug Delivery System · doi:10.2745/dds.35.278
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Guseva, D. S., Rizvanov, A. A., Kiyasov, A. P., & Islamov, R. R. (2013) · Genes and Cells · doi:10.23868/gc120608
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Min, W. (2004) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2003.12.003
Gene Therapy for Vein Graft Disease
Cable, D. G., & Schaff, H. V. (2006) · Springer eBooks · doi:10.1007/3-540-30084-8_41
Lundstrom, K. H. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-818731-9.00137-3
Solter, D., Beyleveld, D., Friele, M. B., Hołówka, J., Lilie, H., Lovell-Badge, R. H., Mandla, C., Martin, U., & Avellaneda, R. P. (2003) · Springer eBooks · doi:10.1007/978-3-662-05117-7_12
Abnormalities of Hepatic Protein Metabolism
A‐Kader, H. H., & Ghishan, F. K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-67293-1.00072-4
Novel Polymer Systems for Gene Therapy
Diaz‐Dussan, D., Peng, Y., & Narain, R. (2022) · doi:10.1002/9783527815562.mme0020
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一种线性化聚乙烯亚胺介导的EGFR靶向siRNA转运系统在人肺腺癌细胞中的优化与评价研究
张萍海, 周磊, 徐欣, et al. (2009) · Science in China Series C-Life Sciences (in Chinese) · doi:10.1360/zc2009-39-12-1128
Strategies and applications of cell surface engineering
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Nanomaterials Mediated Diagnosis of Lung Cancer
Kotha, A. K., Kashikar, R., Famta, P., Shah, S., Srivastava, S., & Chougule, M. B. (2022) · Springer eBooks · doi:10.1007/978-3-031-09636-5_8
Adenovirus vectors for vaccination and cancer gene therapy
Boussettine, R., Hassou, N., Bessi, H., et al. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-85496-2.00029-4
Points to consider for non-clinical safety evaluation of in vivo gene therapy products
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Delivery of Rna Drugs: Beyond the Liver, More than VaccinePreprint
Elnaggar, M. G., He, Y., & Yeo, Y. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4657914
Genetic diagnosis and gene therapy approaches: Current status and limitations
Singh, P., Sharma, S., Haque, F. U., et al. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-22264-1.00002-5
Orchard, P. J., & McIvor, R. S. (2003) · Humana Press eBooks · doi:10.1007/978-1-59259-383-5_14
Abnormalities of Hepatic Protein Metabolism
Elfar, W., & Ghishan, F. K. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-11760-2.00073-2
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Yıldız, U., ALTINOK, İ., Arslan, H., & Çoban, B. (2025) · Journal of Chemical Sciences · doi:10.1007/s12039-025-02436-0
“1,2 For these reasons, non-viral deliveries are attractive alternatives to viral systems for DNA delivery.”
Cell therapy limits loss of vision in an animal model of retinal degenerative disease
McGill, T. J. (2004) · Open ULeth Scholarship (OPUS) (University of Lethbridge)
ナノバイオテクノロジーが先導する診断・治療イノベーション―超分子ナノデバイスによる薬物・遺伝子のピンポイントデリバリー―
有, 松., & Kataoka, K. (2010) · 耳鼻咽喉科展望 · doi:10.11453/orltokyo.53.360
Gene therapy approach on Charcot-Marie-Tooth type 1A rats
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Duyvestyn, J. M., Bredenbeek, P. J., Thaler, M., et al. (2026) · Virology Journal · doi:10.1186/s12985-026-03145-x
“Use of extremely high doses of non-replicating particles caused lethality in a human trial with recombinant adenovirus vector vaccine [13, 38], raising the possibility that increased numbers of non-infectious rUSUV-FVR particles (compared to WT) caused immunopathology and faster death [39].”
Advances in Polyethyleneimine‐Derived Nanoformulations
Attia, M. S., Skwarczyński, M., & Hussein, W. M. (2026) · Small Science · doi:10.1002/smsc.70330 · Cited by 1
“Viral vectors can efficiently deliver genes but are limited by toxicity, immunogenicity, and risk of mutations, prompting research into nonviral delivery systems as safer options [4, 11].”
Base Editing: Mechanisms and Therapeutic Applications
Catalano, F. (2026) · Methods in molecular biology · doi:10.1007/978-1-0716-5547-4_4 · Cited by 1
Noninvasive Delivery of DNA Into the Eye
Nickerson, J. M., Shuler, R. K., Davies, J. B., Dioguardi, P. K., Wolchok, S. M., Ciavatta, V. T., Boatright, J. H., & Edelhauser, H. F. (2006) · Humana Press eBooks · doi:10.1007/978-1-59745-047-8_21
Bot, C. (2012) · OpenGrey (Institut de l'Information Scientifique et Technique)
Doyal, M. F. (2015) · D-Scholarship@Pitt (University of Pittsburgh)
RNA Interference and MicroRNA Modulation for the Treatment of Cardiac Disorders
Poller, W. C., Suckau, L., Pinkert, S., & Fechner, H. (2008) · Springer eBooks · doi:10.1007/978-3-540-78709-9_8
“That tragic event prompted thorough additional investigations (Lehrman 1999; Marshall 2000) into the risks of adenovector-mediated gene therapy including serious adverse events even if they may occur only very rarely, in predisposed individuals, or at very high vector doses.”
BackgroundImmune Reaction Following Cell and Gene Therapy
Tremblay, J. P. (2000) · Birkhäuser Boston eBooks · doi:10.1007/978-1-4612-2126-5_13
Metadata
- Authors
- Lehrman, S.
- Corresponding author
- Lehrman, Sally
- ORCID
- Lehrman, Sally
- Venue
- Nature
- Published
- 1999-10-07
- Volume
- 401
- Issue
- 6753
- Pages
- 517-518
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1606853210
- Cited by
- 576
- References
- 0
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 11 · 2023: 15 · 2022: 17 · 2021: 12 · 2020: 18 · 2019: 16 · 2018: 18 · 2017: 14 · 2016: 14 · 2015: 24 · 2014: 30 · 2013: 23 · 2012: 31
- Type
- other
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DigitalGeorgetown (Georgetown University Library) (submittedVersion)
- Funders
- Brigham and Women's Hospital
- University of East Anglia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Nursing › Issues, ethics and legal aspects › Biomedical Ethics and Regulation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Keywords
- gene therapy, viral vectors, recombinant adeno-associated virus, clinical trial safety
- MeSH terms
- Adenoviridae, Adult, Fever, Genetic Vectors, Humans, Male, Ornithine Carbamoyltransferase, Thrombosis, Genetic Therapy, Clinical Trials, Phase I as Topic, Fatal Outcome, Risk Assessment, Ornithine Carbamoyltransferase Deficiency Disease, Advisory Committees, Government Regulation, Federal Government, Research Subjects
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