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Publication Detail
Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Alonso-Ferrero ME, van Til NP, Bartolovic K, Mata MF, Wagemaker G, Moulding D, Williams DA, Kinnon C, Waddington SN, Milsom MD, Howe SJ
  • Publication date:
    11/09/2017
  • Journal:
    Experimental hematology
  • Medium:
    Print-Electronic
  • Print ISSN:
    0301-472X
  • Language:
    eng
  • Addresses:
    Molecular and Cellular Immunology, UCL Great Ormond Street Institute of Child Health, London, WC1N 1EH. UK.
Abstract
Integration-deficient lentiviruses (IdLV) effectively deliver genes to tissues but are rapidly lost from dividing cells. This property can be harnessed to transiently express transgenes to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of Hematopoietic Stem/Progenitor Cells (HSPC) during transplantation by delivering HOXB4 and Angptl3 using IdLV to enhance the engraftment of HSPC. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduces this risk and those associated with unsolicited gene expression in daughter cells. Transient expression led to increased multilineage hematopoietic engraftment in in vivo competitive repopulation assays, without side-effects reported in constitutive overexpression models. Adult stem cell fate has not previously been programmed using IdLV but we demonstrate these transient gene expression tools can produce clinically relevant alterations or be applied to investigate basic biology.
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