1. A novel intranuclear RNA vector system for long-term stem cell modification
- Author
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Brian Lu, Keizo Tomonaga, William E. Matchett, Yasuhiro Ikeda, Allan B. Dietz, Akiko Makino, and Sara J. Holditch
- Subjects
0301 basic medicine ,RNA virus ,Transgene ,Genetic enhancement ,viruses ,BDV vector ,Genetic Vectors ,iPSCs ,Biology ,Article ,Viral vector ,03 medical and health sciences ,Transduction (genetics) ,Mice ,Genetics ,Animals ,Humans ,Progenitor cell ,Borna disease virus ,Molecular Biology ,mesenchymal stem cells ,Mesenchymal stem cell ,Genetic Diseases, Inborn ,RNA ,Virology ,030104 developmental biology ,Molecular Medicine ,Stem cell ,pluripotent stem cells ,Stem Cell Transplantation - Abstract
Genetically modified stem and progenitor cells have emerged as a promising regenerative platform in the treatment of genetic and degenerative disorders, highlighted by their successful therapeutic use in inherent immunodeficiencies. However, biosafety concerns over insertional mutagenesis resulting from integrating recombinant viral vectors have overshadowed the widespread clinical applications of genetically modified stem cells. Here, we report an RNA-based episomal vector system, amenable for long-term transgene expression in stem cells. Specifically, we used a unique intranuclear RNA virus, Borna disease virus (BDV), as the gene transfer vehicle, capable of persistent infections in various cell types. BDV-based vectors allowed for long-term transgene expression in mesenchymal stem cells (MSCs) without affecting cellular morphology, cell surface CD105 expression, or the adipogenicity of MSCs. Similarly, replication-defective BDV vectors achieved long-term transduction of human induced pluripotent stem cells (iPSCs), while maintaining the ability to differentiate into three embryonic germ layers. Thus, the BDV-based vectors offer a genomic modification-free, episomal RNA delivery system for sustained stem cell transduction.
- Published
- 2015