Immune responses in liver-directed lentiviral gene therapy

  • Andrea Annoni
    San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy
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  • Kevin Goudy
    San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy
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  • Mahzad Akbarpour
    San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy

    Vita-Salute San Raffaele University, Milan, Italy
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  • Luigi Naldini
    San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy

    Vita-Salute San Raffaele University, Milan, Italy
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  • Maria Grazia Roncarolo
    Reprint requests: Maria Grazia Roncarolo, MD, San Raffaele Telethon Institute for Gene Therapy, Via Olgettina, 58, Milan, Italy 20132
    San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy

    Vita-Salute San Raffaele University, Milan, Italy
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Published:January 28, 2013DOI:
      The use of lentiviral vectors (LV)s for in vivo gene therapy is an ideal platform for treating many types of disease. Since LVs can transduce a wide array of cells, support long-term gene expression, and be modified to enhance cell targeting, LVs are a powerful modality to deliver life-long therapeutic proteins. A major limitation facing the use of LVs for in vivo gene therapy is the induction of immune responses, which can reduce the transduction efficiency of LV, eliminate the transduced cells, and inhibit the effect of the therapeutic protein. LV strategies designed to restrict transgene expression to the liver to exploit its naturally tolerogenic properties have proven to significantly reduce the induction of pathogenic immune responses and increase therapeutic efficacy. In this review, we outline the immunological hurdles facing in vivo LV gene therapy and highlight the advantages and limitations of using liver-directed LV gene therapy.


      APC (antigen presenting cell), FoxP3 (forkhead box P3), IL (interleukin), KC (Kupffer cells), LSEC (Liver sinusoidal endothelial cells), LV (lentiviral vector), miR (micro-RNA), TLR (toll-like receptor)
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