Lentiviral vectors for the treatment of primary immunodeficiencies.

[wiskott-aldrich syndrome]

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 , RAG 1 /2 deficiency , X-linked severe combined immunodeficiency (Î³chain deficiency , SCIDX 1 ), X-linked lymphoproliferative disease (XLP ) and immune dysregulation , polyendocrinopathy , enteropathy , X-linked (IPEX ) syndrome .

Diseases
Validation

Diseases presenting "severe combined immunodeficiency" symptom

achondroplasia

alpha-thalassemia

child syndrome

cholangiocarcinoma

junctional epidermolysis bullosa

krabbe disease

omenn syndrome

severe combined immunodeficiency

wiskott-aldrich syndrome

This symptom has already been validated