Alphaviral vectors as gene delivery tools for cancer therapy
Date
2016
Authors
Vasiļevska, Jeļena
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Šī pētījuma mērķis bija optimizēt efektīvu gēnu piegādes stratēģiju peļu krūts karcinomas un melanomas audzēju modeļos, izmantojot rekombinantos alfavīrusu vektorus. Lai gan recSFV vektoriem piemita plaša izplatība pelēs ar audzējiem pēc sistēmiskas vektora ievadīšanas, mēs parādījām, ka dominējoša lokalizācija audzējos var tikt sasniegta, pielāgojot vektora devu. Mēs apstiprinājām, ka neiepakota, pašreplicējoša recRNS var tikt veiksmīgi izmantota kā alternatīva un droša metode gēnu piegādei audzējos. Pastiprināta vektora intratumorāla izplatība un transgēna ekspresija var tikt panākta, izmantojot recSFV kombinācijā ar ķīmijterapijas medikamentu 5- fluoruracilu. Mēs atklājām arī vēža šūnu fiziskās un iekššūnas pārmaiņas, kas var sekmēt alfavīrusu iekļūšanu šūnā un replikāciju. Atslēgas vārdi: alfavīrusu vektori, gēnu piegāde, vēzis, audzēju mikrovide
The aim of this research was to optimize the efficient gene delivery strategy using recombinant alphavirus vectors in mouse mammary carcinoma and melanoma tumor models. Although recSFV vectors had a broad dissemination in tumor-bearing mice upon systemic vector administration, we showed that predominant tumor targeting could be attained via adaptation of vector dose. We confirmed that unpacked self-replicating recRNA can be used successfully as an alternative and safe methodology for gene delivery to the tumor. The enhanced vector intratumoral dissemination and transgene expression can be achieved by combined application of recSFV and chemotherapeutic drug 5-fluorouracil. We also detected intracellular and physical alterations of cancer cells that may promote alphavirus entry and replication. Key words: alphavirus vectors, gene delivery, cancer, tumor microenvironment
The aim of this research was to optimize the efficient gene delivery strategy using recombinant alphavirus vectors in mouse mammary carcinoma and melanoma tumor models. Although recSFV vectors had a broad dissemination in tumor-bearing mice upon systemic vector administration, we showed that predominant tumor targeting could be attained via adaptation of vector dose. We confirmed that unpacked self-replicating recRNA can be used successfully as an alternative and safe methodology for gene delivery to the tumor. The enhanced vector intratumoral dissemination and transgene expression can be achieved by combined application of recSFV and chemotherapeutic drug 5-fluorouracil. We also detected intracellular and physical alterations of cancer cells that may promote alphavirus entry and replication. Key words: alphavirus vectors, gene delivery, cancer, tumor microenvironment
Description
Keywords
Bioloģija , Dzīvās dabas zinātnes , Biology