Date of Award:
Master of Science (MS)
D. Keith Roper
D. Keith Roper
Viruses can efficiently introduce genetic material into a variety of cells through cell infection. Therefore, viral vectors, defined as virus-based gene delivery systems, effectively transfer functional gene constructs to target cells. Among different viral vectors, lentiviral vectors are of interest due to the advantages offered to research and therapeutic applications. Low productivity of lentiviral vectors in mammalian producer cells and high production cost, however, remain barriers to the vectors’ routinary use, particularly in clinical settings.
Since most lentiviral vectors are derived from human immunodeficiency virus type I, their genome has been engineered to increase safety. Nevertheless, modifications of the lentiviral vector genetic material and the characteristics of producer mammalian cells have impacted the efficiency of the lentiviral vector production process. A better understanding of the production process at a molecular level may contribute to the design of safer and more cost-effective manufacture strategies.
This study analyzed the effect of splicing, an important molecular process in human immunodeficiency virus type I propagation, on lentiviral vector productivity; specifically, how modulation of this molecular process corresponds to the production of functional lentiviral vectors. Indole small molecules were previously reported to modify human immunodeficiency virus type I splicing. The similarity between lentiviral vectors and human immunodeficiency virus type I motivated examining whether indoles might also impact lentiviral vectors’ splicing and thus affect the production of functional lentiviral vectors. Results showed that the indole derivative alters the splicing of lentiviral vectors and negatively impacts functional lentiviral vector production. However, disruption by the indole of the early stages of the production process and producer cell cycle seems to have a larger effect on lentiviral vector yield than splicing. These results expand the understanding of splicing in lentiviral vector production in mammalian producer cells.
Mier, Nataly, "Effects of Indole Derivative IDC16 on Cell Proliferation, Transfection, and Alternative Splicing in Production of Lentiviral Vectors by Transient Co-Transfection" (2023). All Graduate Theses and Dissertations, Fall 2023 to Present. 73.
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