Progress and prospects: gene therapy for inherited immunodeficiencies.
Haematopoietic stem cell transplantation (HSCT) is now widely used to treat primary immunodeficiencies (PID). For patients with specific disorders (severe combined immunodeficiency (SCID)-X1, adenosine deaminase deficiency (ADA)-SCID, X-chronic granulomatous disease (CGD) and Wiskott-Aldrich Syndrome (WAS)) who lack a suitable human leukocyte antigen (HLA)-matched donor, gene therapy has offered an important alternative treatment option. The success of gene therapy can be attributed, in part, to the selective advantage offered to gene-corrected cells, the avoidance of graft-versus-host disease and to the use of pre-conditioning in patients with chemotherapy to facilitate engraftment of corrected cells. Adverse events have been encountered and this has led to detailed characterization of retroviral vector integration profiles. A new generation of self-inactivating retroviral and lentiviral vectors have been designed to address these safety concerns, and are at an advanced stage of preparation for the next phase of clinical testing.
Molecular Immunology Unit, UCL Institute of Child Health, London, UK.
W
W
Qasim
H B
HB
Gaspar
A J
AJ
Thrasher
D000818:Animals; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000628:therapy*; D008297:Male; D016254:Mutagenesis, Insertional; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D014923:Wiskott-Aldrich Syndrome / Q000628:therapy