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.
Qasim
W
W
Molecular Immunology Unit, UCL Institute of Child Health, London, UK.
Gaspar
H B
HB
Thrasher
A J
AJ
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