Gene therapy: light is finally in the tunnel.
After two decades of ups and downs, gene therapy has recently achieved a milestone in treating patients with Leber's congenital amaurosis (LCA). LCA is a group of inherited blinding diseases with retinal degeneration and severe vision loss in early infancy. Mutations in several genes, including RPE65, cause the disease. Using adeno-associated virus as a vector, three independent teams of investigators have recently shown that RPE65 can be delivered to retinal pigment epithelial cells of LCA patients by subretinal injections resulting in clinical benefits without side effects. However, considering the whole field of gene therapy, there are still major obstacles to clinical applications for other diseases. These obstacles include innate and immune barriers to vector delivery, toxicity of vectors and the lack of sustained therapeutic gene expression. Therefore, new strategies are needed to overcome these hurdles for achieving safe and effective gene therapy. In this article, we shall review the major advancements over the past two decades and, using lung gene therapy as an example, discuss the current obstacles and possible solutions to provide a roadmap for future gene therapy research.
Programme in Physiology and Experimental Medicine, Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G, 1X8, Canada.
Huibi
H
Cao
Robert S
RS
Molday
Jim
J
Hu
D056704:Adaptive Immunity; D002352:Carrier Proteins / Q000235:genetics; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D018390:Gene Targeting; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007113:Immunity, Innate; D057130:Leber Congenital Amaurosis / Q000235:genetics / Q000628:therapy; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012190:Retroviridae / Q000235:genetics; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005136:Eye Proteins; D008081:Liposomes; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C505032:CFTR protein, human