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• W1551603631 abstract "The introduction of naked plasmid DNA in investigational clinical trials offers advantages over conventional viral delivery vehicles. Recent advances have made DNA expression vectors an attractive option for gene therapy, providing inherent logistical advantages such as scalability and reduced cost. Advances in plasmid purification and delivery methods, as well as optimization of long-term tissue-specific expression, have widened the application of plasmid-based gene therapy to many disease models. The successful human application of plasmid DNA is dependent on the route of delivery, sustained and tissue-specific expression, and the underlying disease. Electroporation-mediated and hydrodynamic injections are the most prevalent modes of plasmid delivery in animal models and clinical trials. Liposome-based delivery vehicles and sonoporation are also applied for in vitro and in vivo DNA delivery. Disease models and therapeutic goals dictate the need for short- or long-term expression levels. Gene replacement, for example, mandates safe long-term expression mediated by stable integration and ongoing promoter activity. Where long-term expression is desired, promoter stability, methylation status, stable integration, and immunogenicity toward plasmid DNA are important considerations. DNA vaccines, on the other hand, may require transient antigen expression sufficient to induce innate and adaptive responses. Therapeutic applications include gene replacement, vaccination, tumor targeting, and neovascularization to treat ischemic and arteriosclerotic conditions, and ex vivo genetic modification for immunotherapy by infusing desired lymphocyte subsets. Safety issues related to DNA-based gene therapy can be categorized as short-term adverse effects on tissues related to the modes of plasmid DNA delivery, the immunogenicity of the transgene, and the potential for deleterious on- and off-target effects. Long-term potential risks stem from genotoxicity arising from genomic integration of the introduced plasmid. For many patients and investigators the risks of toxicity are outweighed by the potential benefits of using plasmids, resulting in a plethora of clinical trials using a non-viral approach to gene therapy." @default.
• W1551603631 created "2016-06-24" @default.
• W1551603631 creator A5007081796 @default.
• W1551603631 creator A5029782492 @default.
• W1551603631 creator A5055549830 @default.
• W1551603631 date "2014-03-01" @default.
• W1551603631 modified "2023-10-16" @default.
• W1551603631 title "DNA Plasmids for Non‐viral Gene Therapy of Cancer" @default.
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