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Lentiviral vectors for the treatment of primary immunodeficiencies

  • ICIEM Symposium 2013
  • Published:
Journal of Inherited Metabolic Disease

Abstract

In the last years important progress has been made in the treatment of several primary immunodeficiency disorders (PIDs) with gene therapy. Hematopoietic stem cell (HSC) gene therapy indeed represents a valid alternative to conventional transplantation when a compatible donor is not available and recent success confirmed the great potential of this approach. First clinical trials performed with gamma retroviral vectors were promising and guaranteed clinical benefits to the patients. On the other hand, the outcome of severe adverse events as the development of hematological abnormalities highlighted the necessity to develop a safer platform to deliver the therapeutic gene. Self-inactivating (SIN) lentiviral vectors (LVVs) were studied to overcome this hurdle through their preferable integration pattern into the host genome. In this review, we describe the recent advancements achieved both in vitro and at preclinical level with LVVs for the treatment of Wiskott-Aldrich syndrome (WAS), chronic granulomatous disease (CGD), ADA deficiency (ADA-SCID), Artemis deficiency, RAG1/2 deficiency, X-linked severe combined immunodeficiency (γchain deficiency, SCIDX1), X-linked lymphoproliferative disease (XLP) and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.

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Acknowledgments

This work was supported by grants from Fondazione Roma (Stem Cells based approaches to monogenic diseases); European Commission (E-rare project EURO-CGD and CELL-PID HEALTH-F5-2010-261387) and Fondazione Telethon (TIGET core grant).

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This article does not contain any studies with human or animal subjects performed by the any of the authors.

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None declared.

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Authors and Affiliations

  1. Department of Pediatrics, Children’s Hospital Bambino Gesù and University of Rome Tor Vergata School of Medicine, Rome, Italy

    Giada Farinelli, Valentina Capo & Alessandro Aiuti

  2. San Raffaele Telethon Institute for Gene Therapy (TIGET), Scientific Institute HS Raffaele, Milan, Italy

    Samantha Scaramuzza & Alessandro Aiuti

  3. Dip. di Medicina dei Sistemi, University of Rome Tor Vergata, Via Montpellier 1, 00133, Roma, Italy

    Alessandro Aiuti

  4. HSR-TIGET, Scientific Institute San Raffaele, Via Olgettina 58, 20132, Milano, Italy

    Alessandro Aiuti

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  1. Giada Farinelli
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  2. Valentina Capo
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  3. Samantha Scaramuzza
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  4. Alessandro Aiuti
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Correspondence to Alessandro Aiuti.

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Communicated by: Jean-Marie Saudubray

Giada Farinelli and Valentina Capo contributed equally to this work

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Farinelli, G., Capo, V., Scaramuzza, S. et al. Lentiviral vectors for the treatment of primary immunodeficiencies. J Inherit Metab Dis 37, 525–533 (2014). https://doi.org/10.1007/s10545-014-9690-y

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