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A novel intranuclear RNA vector system for long-term stem cell modification

Gene Therapy, ISSN: 1476-5462, Vol: 23, Issue: 3, Page: 256-262
2016
  • 15
    Citations
  • 0
    Usage
  • 41
    Captures
  • 1
    Mentions
  • 1
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    15
  • Captures
    41
  • Mentions
    1
    • News Mentions
      1
      • News
        1
  • Social Media
    1
    • Shares, Likes & Comments
      1
      • Facebook
        1

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A novel intranuclear RNA vector system for long-term stem cell modification

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Article Description

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, 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.

Bibliographic Details

Y. Ikeda; W. E. Matchett; S. J. Holditch; B. Lu; A. Makino; K. Tomonaga; A. B. Dietz

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

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