Hematopoietic stem cell gene therapy for adenosine deaminase deficient-SCID.
Gene therapy is a highly attractive strategy for many types of inherited disorders of the immune system. Adenosine deaminase (ADA) deficient-severe combined immunodeficiency (SCID) has been the target of several clinical trials based on the use of hematopoietic stem/progenitor cells engineered with retroviral vectors. The introduction of a low intensity conditioning regimen has been a crucial factor in achieving stable engrafment of hematopoietic stem cells and therapeutic levels of ADA-expressing cells. Recent studies have demonstrated that gene therapy for ADA-SCID has favorable safety profile and is effective in restoring normal purine metabolism and immune functions. Stem cell gene therapy combined with appropriate conditioning regimens might be extended to other genetic disorders of the hematopoietic system.
Aiuti
Alessandro
A
San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) and Pediatric Immunohematology and Bone Marrow Transplant Unit, Scientific Institute HS Raffaele, Via Olgettina 58, 20132, Milan, Italy. a.aiuti@hsr.it
Brigida
Immacolata
I
Ferrua
Francesca
F
Cappelli
Barbara
B
Chiesa
Robert
R
Marktel
Sarah
S
Roncarolo
Maria-Grazia
MG
D000243:Adenosine Deaminase / Q000235:genetics*; D002986:Clinical Trials as Topic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D014161:Transduction, Genetic
D000243:Adenosine Deaminase; C051409:pegademase bovine