title: Clinical gene therapy for the treatment of RPE65-associated Leber congenital amaurosis.
abstract: BACKGROUND
  The positive results of pioneering clinical trials using gene therapy as treatment for patients with Leber congenital amaurosis (LCA) have ushered in a new era of molecular retinal therapeutics for LCA, other blinding retinal disorders and gene therapy applications.
  
  
  METHODS
  This review describes the role of retinal pigment epithelium-specific 65 kDa protein (RPE65) in the visual cycle and how RPE65 deficiency results in LCA; the extensive preclinical studies with recombinant adeno-associated virus (rAAV)-RPE65 gene vectors; and the human rAAV-RPE65 and related gene therapy clinical trials and studies. The literature search included a review of primary sources (e.g., journal articles) that reported study data results and key secondary sources such as meta-reviews available through PubMed, as well as reviews of clinical trial descriptions and results as reported in clinicaltrials.gov, conference publications and news releases.
  
  
  CONCLUSIONS
  LCA-RPE65 gene therapy is an example of successful, innovative, translational research. Further research is needed regarding how retinal gene therapy can be improved.
authors.affiliation: University of Massachusetts Medical School, UMass Memorial Eye Center, Department of Ophthalmology, 281 Lincoln St., Worcester, MA 01605, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Stein
authors.forename: Kamolika
authors.initials: K
authors.lastname: Roy
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Shalesh
authors.initials: S
authors.lastname: Kaushal
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D019317:Evidence-Based Medicine; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D012160:Retina / Q000378:metabolism* / Q000503:physiopathology; D057170:Translational Research, Biomedical; D016896:Treatment Outcome; D014785:Vision, Ocular; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase