Lentiviral vectors for the treatment of primary immunodeficiencies

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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Correspondence to Alessandro Aiuti.

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Giada Farinelli and Valentina Capo contributed equally to this work

Communicated by: Jean-Marie Saudubray

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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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Keywords

  • Enzyme Replacement Therapy
  • Chronic Granulomatous Disease
  • Adenosine Deaminase Deficiency
  • SH2D1A Gene
  • IL2RG Gene