Towards a rAAV-based gene therapy for ADA-SCID: from ADA deficiency to current and future treatment strategies
Gene Therapy Center; Department of Pediatrics
Medical Subject Headings
Adenosine Deaminase; Dependovirus; Gene Therapy; *Genetic Vectors; Humans; Recombinant Proteins; Severe Combined Immunodeficiency
Allergy and Immunology | Genetics and Genomics | Pediatrics | Respiratory Tract Diseases
Adenosine deaminase deficiency fosters a rare, devastating pediatric immune deficiency with concomitant opportunistic infections, metabolic anomalies and multiple organ system pathology. The standard of care for adenosine deaminase deficient severe combined immune deficiency (ADA-SCID) includes enzyme replacement therapy or bone marrow transplantation. Gene therapies for ADA-SCID over nearly two decades have exclusively involved retroviral vectors targeted to lymphocytes and hematopoetic progenitors. These groundbreaking gene therapies represent a revolution in clinical medicine, but come with several challenges, including the risk of insertional mutagenesis. An alternative gene therapy for ADA-SCID may utilize recombinant adeno-associated virus vectors in vivo, with numerous target tissues, to foster ectopic expression and secretion of adenosine deaminase. This review endeavors to describe ADA-SCID, the traditional treatments, previous retroviral gene therapies, and primarily, alternative recombinant adeno-associated virus-based strategies to remedy this potentially fatal genetic disease.
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Citation: Pharmacogenomics. 2008 Jul;9(7):947-68. Link to article on publisher's site