20.500.12556/RUL-130843 Elektroporacija kot sodobni pristop dostave genskih konstruktov pri genski terapiji raka. Electroporation as a modern approach to the delivery of genetic constructs in cancer gene therapy Vodilni vzrok smrti v razvitem svetu je poleg krvožilnih bolezni rak. Po podatkih IARC je leta 2020 na svetu za rakom zbolelo 19,3 milijonov ljudi, 10 milijonov jih je raku podleglo. Rak ali malignom ali maligni tumor je poligenska bolezen, ki nastane kot posledica mutacije ali epigenetske spremembe v dednem zapisu ene same celice in je trenutno še ne znamo pozdraviti. Nov obetajoč pristop zdravljenja raka je genska terapija, pri kateri v tumorske celice administriramo gene, njihove dele, oligonukleotide, miRNA in siRNA z namenom utišanja, znižanja regulacije, modifikacije ali popravljanja tarčnih celic. Terapijo vnašamo in vivo ali ex vivo s pomočjo dostavnih sistemov oz. vektorjev, ki jih grobo delimo na virusne in nevirusne. Velik potencial za transfekcijo celic ima elektroporacija gole plazmidne DNA zaradi varnosti in največje učinkovitosti med nevirusnimi vektorji. Elektroporacija je pojav tvorbe por na celični membrani, kar je posledica izpostavitve celic kratkim visokonapetostnim impulzom. Permeabilizirana membrana omogoča transport molekul različnih velikost v jedro. Po prenehanju delovanja električnega polja se membrana pri reverzibilni elektroporaciji povrne v prvotno stanje v določenem času (od nekaj milisekund do nekaj minut). Elektroporacijo uporabljamo pri imunski elektrogenski terapiji, kjer v tumorske celice vnašamo IL-12 plazmidno DNA. Gre za citokin, ki je zelo močan induktor protitumorske imunosti. Raziskovanje njegovega terapevtskega potenciala že poteka na predklinični in tudi na klinični ravni. Cancer is the leading cause of death in the developed world, alongside circulatory diseases. According to the IARC, 19.3 million people worldwide were diagnosed with cancer in 2020, and 10 million succumbed to cancer. Cancer, or malignancy or malignant tumour, is a polygenic disease that arises as a result of a mutation or epigenetic change in the genome of a single cell, and which currently has no cure. A promising new approach to cancer treatment is gene therapy, in which genes, gene parts, oligonucleotides, miRNAs and siRNAs are administered into tumour cells to silence, down-regulate, modify, or repair target cells. Therapy is administered in vivo or ex vivo using delivery systems or vectors, which are roughly divided into viral and non-viral. The electroporation of naked plasmid DNA has great potential for cell transfection due to its safety and the highest efficiency among non-viral vectors. Electroporation is the phenomenon of pore formation on the cell membrane resulting from the exposure of cells to short high-voltage pulses. The permeabilised membrane allows the transport of molecules of different sizes into the nucleus. After the electric field has ceased, the membrane returns to its original state within a certain time (from a few milliseconds to a few minutes) in reversible electroporation. Electroporation is used in immune electrogene therapy, where IL-12 plasmid DNA is injected into tumour cells. This is a cytokine that is a very potent inducer of antitumour immunity. Its therapeutic potential is already being tested at both pre-clinical and clinical levels. rak genska terapija elektroporacija plazmidna DNA interlevkin-12 IL-12 cancer gene therapy electroporation plasmid DNA interleukin-12 IL-12 true false false [T. Moretti] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2021-09-18 07:16:07 2021-09-18 07:16:12 2022-09-09 04:18:20 0000-00-00 00:00:00 2021 0 Ljubljana 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 606:616-006.6:602.621(043.2) 197194 76801283 19022.pdf 19022.pdf 1 CF0D07D1B554802EEC1106DA41ED267A fa21ec61814d6228b7b03888715e21ead84d59ddc9001d02bb954f12fc5fe01a 4716c8f5-183f-11ec-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=148016 Biotehniška fakulteta 0 0 0