Key result
Self-inactivating lentiviral vectors show preclinical promise as a safer gene therapy for primary immunodeficiencies.
Why the study?
Severe adverse events from gamma retroviral vectors in gene therapy for primary immunodeficiencies highlighted the need for safer gene delivery platforms.
Self-inactivating lentiviral vectors represent a promising and safer gene therapy approach for treating various primary immunodeficiencies in preclinical models.
Not ready for clinical use in primary immunodeficiencies; leaves open translation of self-inactivating lentiviral vectors to human trials.
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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Farinelli et al. (2014) conducted a review in Primary immunodeficiency disorders (PIDs). Self-inactivating (SIN) lentiviral vectors (LVVs) vs. Gamma retroviral vectors was evaluated. Self-inactivating lentiviral vectors are being studied in vitro and at the preclinical level as a safer gene therapy platform for multiple primary immunodeficiency disorders.
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