title: 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.
authors.affiliation: Department of Pediatrics, Children's Hospital Bambino Gesù and University of Rome Tor Vergata School of Medicine, Rome, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Farinelli
authors.forename: Valentina
authors.initials: V
authors.lastname: Capo
authors.forename: Samantha
authors.initials: S
authors.lastname: Scaramuzza
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency / Q000235:genetics; D000361:Agammaglobulinemia / Q000235:genetics / Q000628:therapy; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use*; D006105:Granulomatous Disease, Chronic / Q000235:genetics / Q000628:therapy; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000628:therapy; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000628:therapy
chemical_list: D000243:Adenosine Deaminase