Biodistribution and Safety Studies of a Bicistronic Plasmid for Nerve Repair
| Autor: | Vadim Balabanyan, Yulii V. Shidlovskii, Stalik Dzhauari, Veronika Yu. Sysoeva, Maxim Karagyaur, Dmitry Stambolsky, Eugene N. Kozlov, Vladimir Popov, E. V. Semina, Alexandra Rostovtseva, Lyubov A. Lebedeva, Polina Klimovich |
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| Rok vydání: | 2021 |
| Předmět: |
Biodistribution
Genetic enhancement 0206 medical engineering Biomedical Engineering Medicine (miscellaneous) Bioengineering 02 engineering and technology Regenerative medicine Mice 03 medical and health sciences Plasmid Animals Medicine Tissue Distribution Nerve repair 030304 developmental biology 0303 health sciences Safety studies business.industry Therapeutic effect DNA 020601 biomedical engineering Rats Cancer research Female business Plasmids |
| Zdroj: | Tissue Engineering Part C: Methods. 27:391-400 |
| ISSN: | 1937-3392 1937-3384 |
| Popis: | Gene therapy is one of the promising approaches for regenerative medicine. Local and long-term expression of essential growth factors allows to achieve the desired therapeutic effect. However, some aspects of prolonged usage of genetic constructs encoding growth factors, such as toxicity, mutagenicity, genotoxicity, and ability to disseminate from the injection site and mediate ectopic expression of therapeutic proteins, are poorly investigated. These aspects of gene therapy drugs' usage became the subject of this study. To study plasmid biodistribution, toxicity, mutagenicity, and genotoxicity, we used previously described bicistronic genetic construct encoding human brain-derived neurotrophic factor (hBDNF) and human urokinase plasminogen activator (huPA) for nerve repair. Biodistribution studies were conducted in mice: a course of intramuscular plasmid injections was followed by the study of the content of the plasmid (real-time polymerase chain reaction) and recombinant proteins (enzyme-linked immunosorbent assay) in murine organs and tissues. The study of the plasmid chronic toxicity was carried out on rats with registration of their weight dynamics, neurological status, emotional state, and blood test parameters. The mutagenicity of the plasmid was studied in an |
| Databáze: | OpenAIRE |
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