title: Towards a rAAV-based gene therapy for ADA-SCID: from ADA deficiency to current and future treatment strategies.
abstract: 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.
authors.affiliation: University of Florida College of Medicine, Department of Pediatrics, Gainesville, FL 32607, USA. jsilver007@yahoo.com
authors.forename: Jared N
authors.initials: JN
authors.lastname: Silver
authors.forename: Terence R
authors.initials: TR
authors.lastname: Flotte
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000201:enzymology / Q000235:genetics / Q000628:therapy*
chemical_list: D011994:Recombinant Proteins; D000243:Adenosine Deaminase