Virus treatment questioned after gene therapy death
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Viral vectors have fundamental shortcomings, including risk of carcinogenesis, limited insertion size, immune responses, and difficulty in large-scale production, which severely limit their further applications.
“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]
Zuris et al.'s injection of Cas9:sgRNA complexes targeting GFP gene into the cochlea of transgenic Atoh1-GFP mice resulted in ~20% Cas9-mediated genome modification in hair cells.
“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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Dufès, C., Uchegbu, I. F., & Schätzlein, A. G. (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2005.09.017 · Cited by 984 · see citing works
“The fact that an adenoviral therapy for direct injection into head and neck cancer has been licensed recently in China [1] is just one indication of this, while highly publicised reports of the risks of some genetic therapies serve as a reminder of some of the potential risks of this emerging therapeutic approach [2,3…”
BackgroundPolyethylenimine-based non-viral gene delivery systems
Lungwitz, U., Breunig, M., Blunk, T., & Göpferich, A. M. (2005) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2004.11.011 · Cited by 985 · see citing works
The role of nitric oxide in cancer
Xu, W., Liu, L.-Z., Loizidou, M., Ahmed, M., & Charles, I. G. (2002) · Cell Research · doi:10.1038/sj.cr.7290133 · Cited by 829 · see citing works
Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes
Wahlgren, J., Karlson, T. D. L., Brisslert, M., Sani, F. V., Telemo, E., Sunnerhagen, P., & Valadi, H. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks463 · Cited by 716 · see citing works
Lee, C. S., Bishop, E. S., Zhang, R., Yu, X., Farina, E. M., Yan, S., Zhao, C., Zeng, Z., Shu, Y., Wu, X., et al. (2017) · Genes & Diseases · doi:10.1016/j.gendis.2017.04.001 · Cited by 691 · see citing works
Nitric oxide and cancer: a review
Choudhari, S. K., Chaudhary, M. S., Bagde, S., Gadbail, A. R., & Joshi, V. (2013) · World Journal of Surgical Oncology · doi:10.1186/1477-7819-11-118 · Cited by 638 · see citing works
“However, as both retroviral and adenoviral vectors may be hazardous to the host, cell-based approaches to overcome the problems associated with gene therapy [102] are being sought.”
BackgroundImmune responses to gene therapy vectors: influence on vector function and effector mechanisms
Bessis, N., Garcia-Cozar, F. J., & Boissier, M. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302364 · Cited by 636 · see citing works
Rampling, R. P., Cruickshank, G., Papanastassiou, V., Nicoll, J. A. R., Hadley, D. M., Brennan, D., Petty, R., MacLean, A. G., Harland, J., McKie, E. A., et al. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301184 · Cited by 594 · see citing works
Polymeric nanomedicine for cancer therapy
Park, J. H., Lee, S., Kim, J.-H., Park, K., Kim, K., & Kwon, I. C. (2008) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2007.09.003 · Cited by 506 · see citing works
Evolution of drug delivery systems: From 1950 to 2020 and beyond
Park, H., Otte, A., & Park, K. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.12.030 · Cited by 478 · see citing works
Biodegradable polymers as non-viral carriers for plasmid DNA delivery
Luten, J., van Nostrum, C. F., Smedt, S. C. D., & Hennink, W. E. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.10.028 · Cited by 471 · see citing works
Losordo, D. W., Vale, P. R., Hendel, R. C., et al. (2002) · Circulation · doi:10.1161/01.cir.0000015982.70785.b7 · Cited by 469 · see citing works
Nano-oncology: drug delivery, imaging, and sensing
Portney, N. G., & Ozkan, M. (2006) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-005-0247-7 · Cited by 457 · see citing works
Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities
Li, L., Hu, S., & Chen, X. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.04.031 · Cited by 415 · see citing works
“This system resulted in ~20% Cas9-mediated genome modification in hair cells [69].”
Gemini Surfactants: New Synthetic Vectors for Gene Transfection
Kirby, A. J., Camilleri, P., Engberts, J. B. F. N., et al. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200201597 · Cited by 414 · see citing works
Precise nanomedicine for intelligent therapy of cancer
Chen, H., Gu, Z., An, H., Chen, C., Chen, J., Cui, R., Chen, S., Chen, W., Chen, X., Chen, X. S., et al. (2018) · Science China Chemistry · doi:10.1007/s11426-018-9397-5 · Cited by 409 · see citing works
Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects
Huang, Z., Fu, J., & Zhang, Y. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01672 · Cited by 415 · see citing works
Gene transfer as a tool to induce therapeutic vascular growth
Ylä‐Herttuala, S., & Alitalo, K. K. (2003) · Nature Medicine · doi:10.1038/nm0603-694 · Cited by 400 · see citing works
“In retrospect, the death seems to have been a result of toxicity caused by the adenoviral vector in conjunction with the underlying diseas”
BackgroundHigh prevalence of Streptococcus pyogenes Cas9-reactive T cells within the adult human population
Wagner, D. L., Amini, L., Wendering, D. J., Burkhardt, L.-M., Akyüz, L., Reinke, P., Volk, H.-D., & Schmueck-Henneresse, M. (2019) · Nature Medicine · doi:10.1038/s41591-018-0204-6 · Cited by 399 · see citing works
Knopp, D., Tang, D., & Nießner, R. (2009) · Analytica Chimica Acta · doi:10.1016/j.aca.2009.05.037 · Cited by 380 · see citing works
Ylä‐Herttuala, S., & Martin, J. F. (2000) · The Lancet · doi:10.1016/s0140-6736(99)04180-x · Cited by 375 · see citing works
Polymeric nanostructured materials for biomedical applications
Tang, Z., He, C., Tian, H., Ding, J., Hsiao, B. S., Chu, B., & Chen, X. (2016) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2016.05.005 · Cited by 364 · see citing works
Wang, D., Mou, H., Li, S., Li, Y., Hough, S., Tran, K., Li, J., Yin, H., Anderson, D. G., Sontheimer, E. J., et al. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.087 · Cited by 345 · see citing works
“Ad vectors for human gene therapy have been hampered by their destructive immunotoxicity.(27) However, they may be well-suited to deliver the CRISPR/Cas9 gene-editing system to model organisms such as mouse.”
Developments in liposomal drug delivery systems
Maurer, N., Fenske, D. B., & Cullis, P. R. (2001) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.1.6.923 · Cited by 344 · see citing works
“However, they can generate a strong immune response and are not suited to systemic delivery [172].”
BackgroundRNA Interference: From Basic Research to Therapeutic Applications
Kurreck, J. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200802092 · Cited by 332 · see citing works
Polyethylenimine: A versatile, multifunctional non-viral vector for nucleic acid delivery
Pandey, A. P., & Sawant, K. K. (2016) · Materials Science and Engineering C · doi:10.1016/j.msec.2016.07.066 · Cited by 303 · see citing works
Virus-mediated gene delivery for human gene therapy
Giacca, M., & Zacchigna, S. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.04.008 · Cited by 302 · see citing works
Guy, B., Guirakhoo, F., Barban, V., et al. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.09.098 · Cited by 291 · see citing works
Production and clinical development of nanoparticles for gene delivery
Chen, J., Guo, Z., Tian, H., & Chen, X. (2016) · Molecular Therapy - Methods & Clinical Development · doi:10.1038/mtm.2016.23 · Cited by 274 · see citing works
Nucleic acid delivery with chitosan and its derivatives
Lai, W., & Lin, M. C. M. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.11.021 · Cited by 243 · see citing works
“Though viral vectors have the merit of high transfectability, their potential safety risks [5,6] as well as immunogenicity warrant the search for alternative non-viral vectors [7].”
BackgroundGraham, B. S. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00972.x · Cited by 239 · see citing works
“The first is a historical association with a highly publicized adverse outcome in a gene therapy study (117).”
BackgroundIn vivo gene delivery mediated by non-viral vectors for cancer therapy
Mohammadinejad, R., Dehshahri, A., Madamsetty, V. S., Zahmatkeshan, M., Tavakol, S., Makvandi, P., Khorsandi, D., Pardakhty, A., Ashrafizadeh, M., Afshar, E. G., et al. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.06.038 · Cited by 238 · see citing works
“These carriers are called as non-viral vectors and must be able to interact with nucleic acids to condense them outside the cells and protect the genetic materials from various degrading factors [12,13].”
Han, Y., & Wang, Y. (2011) · Physical Chemistry Chemical Physics · doi:10.1039/c0cp01196g · Cited by 222 · see citing works
Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection
Morizono, K., Xie, Y., Ringpis, G.-E. E., Johnson, M., Nassanian, H., Lee, B., Wu, L., & Chen, I. S. Y. (2005) · Nature Medicine · doi:10.1038/nm1192 · Cited by 220 · see citing works
“Finally, targeting of specific cells and tissues would greatly enhance the safety of gene therapeutic applications by reducing inadvertent infection of irrelevant cells or tissues that has resulted in serious adverse effects in some clinical trial”
BackgroundOsada, K., Christie, R. J., & Kataoka, K. (2009) · Journal of The Royal Society Interface · doi:10.1098/rsif.2008.0547.focus · Cited by 218 · see citing works
“However, problems associated with immune response (Lehrman 1999; Marshall 1999) as well as the possibility of recombination with endogenous genes leading to”
BackgroundA Historical Review of Brain Drug Delivery
Pardridge, W. M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061283 · Cited by 219 · see citing works
Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure
Suzuki, R., Namai, E., Oda, Y., 功人, 西., Otake, S., Koshima, R., Hirata, K., Taira, Y., Utoguchi, N., Negishi, Y., et al. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.10.027 · Cited by 207 · see citing works
Challenges in CRISPR/CAS9 delivery: potential roles of nonviral vectors
Li, L., He, Z.-Y., Wei, X.-W., Gao, G.-P., & Wei, Y.-Q. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.069 · Cited by 202 · see citing works
Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions
Elsabahy, M., Nazarali, A. J., & Földvári, M. (2011) · Current Drug Delivery · doi:10.2174/156720111795256174 · Cited by 199 · see citing works
“The use of viral vectors for gene therapy can be associated with severe inflammation and immunological problems [11,12].”
BackgroundGene transfection of hyperbranched PEI grafted by hydrophobic amino acid segment PBLG
Tian, H., Xiong, W. H., Wei, J., Wang, Y., Chen, X., Jing, X., & Zhu, Q. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.02.027 · Cited by 193 · see citing works
Current status of pharmaceutical and genetic therapeutic approaches to treat DMD.
Pichavant, C., Aartsma-Rus, A., Clemens, P., Davies, K., Dickson, G., Takeda, S., Wilton, S., Wolff, J., Wooddell, C., Xiao, X., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2011.59 · Cited by 202 · see citing works
Yuan, P., Liu, C., Zhang, Z., Liu, K. L., Chen, J., & Li, J. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.07.038 · Cited by 184 · see citing works
Lee, J. H., Lim, Y., Choi, J. S., et al. (2003) · Bioconjugate Chemistry · doi:10.1021/bc034095g · Cited by 179 · see citing works
In vivo delivery of caspase-8 or Fas siRNA improves the survival of septic mice
Szollosi, D. E., Chung, C., Lomas‐Neira, J., Doughty, L., Gregory, S. H., & Ayala, A. (2005) · Blood · doi:10.1182/blood-2004-10-4086 · Cited by 177 · see citing works
Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration
Liu, S., Zhou, J., Zhang, X., Liu, Y., Chen, J., Hu, B., Song, J., & Zhang, Y. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17060982 · Cited by 177 · see citing works
“One of the effective and controllable methods to apply growth factors that can augment stem cell treatments is genetic manipulation of the cells overexpressing diverse growth factors before implantation [57,58].”
Recent Advances in Lipid Nanoparticles for Delivery of mRNA
Yang, L., Gong, L., Wang, P., Zhao, X., Zhao, F. H., Zhang, Z., Li, Y., & Huang, W. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14122682 · Cited by 178 · see citing works
“However, the boom in gene therapy using viral vectors came to an abrupt end when Jesse Gelsinger, an 18-year-old patient with ornithine transcarbamyltransferase deficiency (OTC), died four days later due to multiple organ failure in a phase I clinical trial led by James Wilson of the University of Pennsylvania after r…”
BackgroundLiu, Y., Li, J., Shao, K., Huang, R., Ye, L., Lou, J., & Jiang, C. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.03.011 · Cited by 172 · see citing works
“Despite viral gene vectors have been proved to be efficient enough, the safety consideration has somehow prevented their further applications [8].”
BackgroundThe future of human gene therapy
Rubanyi, G. M. (2001) · Molecular Aspects of Medicine · doi:10.1016/s0098-2997(01)00004-8 · Cited by 167 · see citing works
Dendritic vectors for gene transfection
Guillot-Nieckowski, M., Eisler, S., & Diederich, F. (2006) · New Journal of Chemistry · doi:10.1039/b614877h · Cited by 165 · see citing works
Morral, N., O’Neal, W. K., Rice, K., Leland, M. M., Piedra, P. A., Aguilar-Córdova, E., Carey, K. D., Beaudet, A. L., & Langston, C. (2002) · Human Gene Therapy · doi:10.1089/10430340152712692 · Cited by 163 · see citing works
“Most importantly, the human fatality that occurred after intravascular administration involved a vector deleted for both E1 and E4 (Batshaw et al ., 1999; Lehrman, 1999).”
Yuan, P., Hu, Q., Tang, G., & Li, J. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.03.071 · Cited by 154 · see citing works
Intervertebral disc degeneration—Current therapeutic options and challenges
Samanta, A., Lufkin, T., & Kraus, P. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1156749 · Cited by 162 · see citing works
Gene Therapy for the Heart Lessons Learned and Future Perspectives
Cannata, A. N., Ali, H., Sinagra, G., & Giacca, M. (2020) · Circulation Research · doi:10.1161/circresaha.120.315855 · Cited by 153 · see citing works
Poon, L. C.-H., Zandberg, W. F., Hsiao, D., et al. (2010) · ACS Nano · doi:10.1021/nn1016346 · Cited by 151 · see citing works
The Apoptotic Pathway as a Therapeutic Target in Sepsis
Szollosi, D. E., Swan, R. Z., Chung, C., & Ayala, A. (2007) · Current Drug Targets · doi:10.2174/138945007780362764 · Cited by 149 · see citing works
Wang, J., & Puel, J. (2018) · Physiological Reviews · doi:10.1152/physrev.00053.2017 · Cited by 146 · see citing works
“The first death from a gene therapy was related to the inflammatory reaction to the adenoviral vector (236).”
BackgroundManilla, P., Rebello, T., Afable, C., Lü, X., Slepushkin, V., Humeau, L. M. P. F., Schonely, K., Ni, Y., Binder, G. K., Levine, B. L., et al. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.17 · Cited by 149 · see citing works
“These concerns arose after the death in 1999 of a patient undergoing a University of Pennsylvania gene therapy trial for ornithine transcarboxylase deficiency (OTCD) (Lehrman, 1999).”
InfluentialLong-Circulating Polymeric Nanovectors for Tumor-Selective Gene Delivery
Kommareddy, S., Tiwari, S. B., & Amiji, M. M. (2005) · Technology in Cancer Research & Treatment · doi:10.1177/153303460500400605 · Cited by 146 · see citing works
Liu, Q., Wang, C., Zheng, Y., Zhao, Y., Wang, Y., Hao, J., Zhao, X., Yi, K., Shi, L., Kang, C., et al. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120275 · Cited by 145 · see citing works
Kommareddy, S., & Amiji, M. M. (2007) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2006.11.005 · Cited by 144 · see citing works
“There are reported incidents of insertional mutagenesis during treatment in humans, and their safety is an issue [3-5].”
BackgroundMolecular Dynamics Simulations of DNA/PEI Complexes: Effect of PEI Branching and Protonation State
Sun, C., Tang, T., Uludağ, H., et al. (2011) · Biophysical Journal · doi:10.1016/j.bpj.2011.04.045 · Cited by 143 · see citing works
“However, their toxicity and immunogenicity greatly limit their general use (5).”
Nanoparticles for Gene Delivery
Tian, H., Chen, J., & Chen, X. (2013) · Small · doi:10.1002/smll.201202485 · Cited by 140 · see citing works
Sleeping beauty transposon-mediated gene therapy for prolonged expression.
Hackett, P. B., Ekker, S. C., Largaespada, D., & McIvor, R. (2005) · Advances in Genetics · doi:10.1016/s0065-2660(05)54009-4 · Cited by 136 · see citing works
Drug and Gene Delivery Based on Supramolecular Assembly of PEG-Polypeptide Hybrid Block Copolymers
Osada, K., & Kataoka, K. (2006) · Springer eBooks · doi:10.1007/12_084 · Cited by 136 · see citing works
Cell Transplantation as a Treatment for Retinal Disease
Lund, R. D., Kwan, A., Keegan, D., Sauvé, Y., Coffey, P. J., & Lawrence, J. M. (2001) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(01)00003-9 · Cited by 132 · see citing works
Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo
Aigner, A. M. (2006) · BioMed Research International · doi:10.1155/jbb/2006/71659 · Cited by 130 · see citing works
Cystic Fibrosis Gene Therapy: Looking Back, Looking Forward
Cooney, A. L., McCray, P., & Sinn, P. (2018) · Genes · doi:10.3390/genes9110538 · Cited by 118 · see citing works
“He received a dose of 3.8 × 10 13 viral particles via the femoral artery for delivery to the liver [67] [68] [69] .”
MethodInfluentialGene transfer strategies in tissue engineering
Bleiziffer, O., Eriksson, E. K., Yao, F., Horch, R. E., & Kneser, U. (2007) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2007.00027.x · Cited by 126 · see citing works
“Large-scale transduction of target cells is most efficiently achieved using adenovirus a high titres, which involves the risk of vector toxicity [97].”
BackgroundDegradable polyethylenimines as DNA and small interfering RNA carriers
Jere, D., Jiang, H., Arote, R. B., Kim, Y., Choi, Y., Cho, M., Akaike, T., & Cho, C. S. (2009) · Expert Opinion on Drug Delivery · doi:10.1517/17425240903029183 · Cited by 120 · see citing works
“To date, viral vectors have been tried in the majority of clinical trials because of their high in-vitro and in-vivo transfection capacity, Unfortunately, their application to human gene therapy is limited by several drawbacks; for example, high immunogenicity, activation of viral components, and complex and expensive…”
BackgroundToxicity of a First-Generation Adenoviral Vector in Rhesus Macaques
Lozier, J. N., Csákó, G., Mondoro, T. H., Krizek, D. M., Metzger, M. E., Costello, R., Vostal, J. G., Rick, M. E., Donahue, R. E., & Morgan, R. A. (2002) · Human Gene Therapy · doi:10.1089/10430340152712665 · Cited by 120 · see citing works
“It is noteworthy that adenovirus vectors administered intravenously have significant tropism for lung and liver (Smith et al ., 1993), and lung damage may have occurred in the recently described death of an adenovirus-OTC vector recipient (Lehrman, 1999).”
Biodegradable Inorganic Nanostructured Biomaterials for Drug Delivery
Cai, A., Zhu, Y., & Qi, C. (2020) · Advanced Materials Interfaces · doi:10.1002/admi.202000819 · Cited by 119 · see citing works
Yamamoto, M., Alemany, R., Adachi, Y., et al. (2001) · Molecular Therapy · doi:10.1006/mthe.2001.0275 · Cited by 119 · see citing works
Clonal Propagation of Primate Offspring by Embryo Splitting
Chan, A. W. S., Dominko, T., Luetjens, C. M., et al. (2000) · Science · doi:10.1126/science.287.5451.317 · Cited by 118 · see citing works
Wan, T. Y., Niu, D., Wu, C., Xu, F., Church, G. M., & Yuan, P. (2019) · Materials Today · doi:10.1016/j.mattod.2018.12.003 · Cited by 118 · see citing works
Dehshahri, A., Oskuee, R. K., Shier, W. T., Hatefi, A., & Ramezani, M. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.04.036 · Cited by 116 · see citing works
Chitosan based oligoamine polymers: Synthesis, characterization, and gene delivery
Lu, B., Wang, C., Wu, D., et al. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.03.004 · Cited by 113 · see citing works
Harm, ethics committees and the gene therapy death
Savulescu, J. (2001) · Journal of Medical Ethics · doi:10.1136/jme.27.3.148 · Cited by 113 · see citing works
“adenovirus vector particles containing a gene to correct the genetic defect. He was the eighteenth and final patient in the trial. The virus particles were injected directly into the liver. He received the largest number of virus particles in a gene therapy trial.”
BackgroundFrom bench to bedside for gene-directed enzyme prodrug therapy of cancer
Dachs, G. U., Tupper, J., & Tozer, G. M. (2005) · Anti-Cancer Drugs · doi:10.1097/00001813-200504000-00001 · Cited by 113 · see citing works
Microencapsulated iNOS‐expressing cells cause tumor suppression in mice
Xu, W., Liu, L., & Charles, I. G. (2001) · The FASEB Journal · doi:10.1096/fj.01-0590fje · Cited by 111 · see citing works
“R ecent difficulties with virus-based gene therapy strategies have highlighted the need to explore new approaches for the therapeutic delivery of genes (1).”
BackgroundIntratumoral injection of IL-12 plasmid DNA – results of a phase I/IB clinical trial
Mahvi, D. M., Henry, M. B., Albertini, M. R., et al. (2007) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7701064 · Cited by 108 · see citing works
The gene transfection efficiency of a folate–PEI600–cyclodextrin nanopolymer
Yao, H., Ng, S. S., Tucker, W., Tsang, Y.-K.-T., Man, K., Wang, X., Chow, B., Kung, H., Tang, G., & Lin, M. C. M. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.06.051 · Cited by 107 · see citing works
Lu, B., Xu, X., Zhang, X., Cheng, S., & Zhuo, R. (2008) · Biomacromolecules · doi:10.1021/bm8004676 · Cited by 105 · see citing works
Advancing Nonviral Gene Delivery: Lipid- and Surfactant-Based Nanoparticle Design Strategies
Donkuru, M., Badea, I., Wettig, S. D., Verrall, R. E., Elsabahy, M., & Földvári, M. (2010) · Nanomedicine · doi:10.2217/nnm.10.80 · Cited by 103 · see citing works
Mashel, T., Tarakanchikova, Y., Muslimov, A., Zyuzin, M., Timin, A., Lepik, K., & Fehse, B. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120282 · Cited by 92 · see citing works
Gene therapy: targeting the myocardium
Lyon, A. R., Sato, M., Hajjar, R. J., Samulski, R. J., & Harding, S. E. (2007) · Heart · doi:10.1136/hrt.2007.116483 · Cited by 97 · see citing works
Qian, Y. J., Zha, Y., Feng, B. C., Pang, Z., Zhang, B., Sun, X., Ren, J., Zhang, C., Shao, X., Zhang, Q., et al. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.11.050 · Cited by 97 · see citing works
Lao, Y., Li, M., Gao, M. A., Shao, D., Chi, C., Huang, D., Chakraborty, S., Ho, T., Jiang, W., Wang, H., et al. (2018) · Advanced Science · doi:10.1002/advs.201700540 · Cited by 94 · see citing works
Cellular uptake of DNA–chitosan nanoparticles: The role of clathrin- and caveolae-mediated pathways
Garaiová, Z., Strand, S. P., Reitan, N. K., et al. (2012) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2012.08.016 · Cited by 96 · see citing works
Molecular Dynamics Simulations of DNA-Polycation Complex Formation
Ziebarth, J. D., & Wang, Y. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2009.03.069 · Cited by 96 · see citing works
“However, because of immunoresponses and other safety concerns caused by viral vectors (3,4), there has been a recent focus on developing nonviral gene therapy vectors.”
BackgroundFamilial hypercholesterolemia: A review
Varghese, M. J. (2014) · Annals of Pediatric Cardiology · doi:10.4103/0974-2069.132478 · Cited by 95 · see citing works
“However, due to the problems related to appropriate gene vector, lack of persistent gene expression as well as due to safety concerns,[80] this modality failed to demonstrate substantial clinical efficacy in preliminary trials.”
BackgroundXu, J., Dai, W.-J., Wang, Z., Chen, B., Li, Z., & Fan, X. (2010) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00263-10 · Cited by 94 · see citing works
“Although viral vectors have the merit of high transfectability, their potential safety risks (23) as well as immunogenicity hinder the extensive use of viral vectors in gene therapy and vaccination.”
BackgroundCRISPR/Cas9 delivery with one single adenoviral vector devoid of all viral genes
Ehrke‐Schulz, E., Schiwon, M., Leitner, T., Dávid, S., Bergmann, T., Liu, J., & Ehrhardt, A. (2017) · Scientific Reports · doi:10.1038/s41598-017-17180-w · Cited by 93 · see citing works
Xie, X., Zhao, X., Liu, Y., et al. (2001) · PubMed · Cited by 93 · see citing works
Oskuee, R. K., Dehshahri, A., Shier, W. T., & Ramezani, M. (2009) · The Journal of Gene Medicine · doi:10.1002/jgm.1374 · Cited by 92 · see citing works
Elsabahy, M., & Wooley, K. L. (2012) · Journal of Polymer Science Part A Polymer Chemistry · doi:10.1002/pola.25955 · Cited by 90 · see citing works
Ye, L., Haider, H. K., Tan, R., Toh, W., Law, P. K., Tan, W., Su, L., Zhang, W., Ge, R., Zhang, Y., et al. (2007) · Circulation · doi:10.1161/circulationaha.106.680124 · Cited by 89 · see citing works
Using nuclear targeting signals to enhance non‐viral gene transfer
Chan, C., & Jans, D. A. (2002) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.2002.01061.x · Cited by 89 · see citing works
Kaul, G., & Amiji, M. M. (2004) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20216 · Cited by 89 · see citing works
Hiltunen, M., Turunen, M. P., Turunen, A., et al. (2000) · The FASEB Journal · doi:10.1096/fj.00-0145com · Cited by 88 · see citing works
“It has recently been realized that severe safety problems may be associated with adenovirus-mediated gene therapy (16) and that some of the side effects may be caused be systemic spread and expression of the adenoviruses in ectopic tissues.”
BackgroundInteractions Between DNA and Gemini Surfactant: Impact on Gene Therapy: Part I
Ahmed, T., Kamel, A. O., & Wettig, S. D. (2016) · Nanomedicine · doi:10.2217/nnm.15.203 · Cited by 87 · see citing works
- 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 › Medicine › Physiology › 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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