Original Article | Published:

Shedding of clinical-grade lentiviral vectors is not detected in a gene therapy setting

Gene Therapy volume 22, pages 496502 (2015) | Download Citation

Abstract

Gene therapy using viral vectors that stably integrate into ex vivo cultured cells holds great promises for the treatment of monogenic diseases as well as cancer. However, carry-over of infectious vector particles has been described to occur upon ex vivo transduction of target cells. This, in turn, may lead to inadvertent spreading of viral particles to off-target cells in vivo, raising concerns for potential adverse effects, such as toxicity of ectopic transgene expression, immunogenicity from in vivo transduced antigen-presenting cells and, possibly, gene transfer to germline cells. Here, we have investigated factors influencing the extent of lentiviral vector (LV) shedding upon ex vivo transduction of human hematopoietic stem and progenitor cells. Our results indicate that, although vector carry-over is detectable when using laboratory-grade vector stocks, the use of clinical-grade vector stocks strongly decreases the extent of inadvertent transduction of secondary targets, likely because of the higher degree of purification. These data provide supportive evidence for the safe use of the LV platform in clinical settings.

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Acknowledgements

This work was supported by Fondazione Telethon (TIGET grant B2), the European Leukodystrophy Foundation (ELA 2007-00515) and Italian Ministry of Health (Progetto Giovani Ricercatori GR-2008-57) to AB. We thank GlaxoSmithKline R&D division for critical reading of the manuscript prior to submission.

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Affiliations

  1. Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy

    • M Cesani
    • , T Plati
    • , L Lorioli
    • , F Benedicenti
    • , D Redaelli
    • , F Dionisio
    • , L Biasco
    • , E Montini
    • , L Naldini
    •  & A Biffi
  2. Vita-Salute San Raffaele University, Milan, Italy

    • L Lorioli
    •  & L Naldini

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The authors declare no conflict of interest.

Corresponding author

Correspondence to A Biffi.

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DOI

https://doi.org/10.1038/gt.2015.10

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