Current Gene Therapy - Volume 10, Issue 5, 2010

This special issue was meant to provide a comprehensive review on AAV-mediated retinal gene therapy from vector design to current clinical applications. There has been a great progress over the past decade in generating and characterizing animal models for retinal disorders, developing and testing strategies for ameliorating the disease process and moving the promising proof-of-concept data into clinical trials Read More

Adeno-Associated Virus based vectors (rAAV) are advantageous for human gene therapy due to low inflammatory responses, lack of toxicity, natural persistence, and ability to transencapsidate the genome allowing large variations in vector biology and tropism. Over sixty clinical trials have been conducted using rAAV serotype 2 for gene delivery with a number demonstrating success in immunoprivileged sites, includin Read More

Recombinant adeno-associated virus (AAV) -based vectors expressing therapeutic gene products have shown great promise for human gene therapy. A recent milestone has been the safety and efficacy observed using recombinant AAV2 expressing retinal pigment epithelial associated 65KDa protein for Leber Congenital Amaurosis. This review summarizes manufacturing and characterization of ‘AAV2-hRPE65v2’, the ve Read More

Retinal blinding disorders together have a prevalence of 1 in 2000 humans world wide and represent a significant impact on the quality of life as well as the possibility to attain personal achievements. Mutations in genes that are expressed either in RPE cells, photoreceptors or bipolar cells can cause varying forms of degenerative or stationary retinal disorders, as the presence of the encoded proteins is crucial for normal functi Read More

Common blinding diseases that are currently untreatable include conditions characterized by progressive neuronal degeneration, such as retinitis pigmentosa, Leber congenital amaurosis or glaucoma, and characterized by ocular neovascularization, like wet age-related macular degeneration, proliferative diabetic retinopathy and retinopathy of prematurity. The pathogenic mechanisms underlying either neuronal degeneration Read More

Over the past two decades, significant progress has been made in defining the molecular pathogenesis of hereditary retinal degenerations. Many of these are characterised by immense genetic heterogeneity. For example, in retinitis pigmentosa (RP), the most common form of this group of disorders, approximately 50 disease causing genes have been implicated, 20 of which are inherited in an autosomal dominant manner. Read More

Inherited retinal diseases are non-lethal and have a wide level of genetic heterogeneity. Many of the genes involved have now been identified and their function elucidated, providing a major step towards the development of genebased treatments. The most widely used vectors for ocular gene delivery are based on adeno-associated virus (AAV) because they mediate long-term transgene expression in a variety of retinal cell typ Read More

Gene therapy utilizing retroviral vectors is being postulated as a real therapeutic alternative for many hemopoietic inherited diseases, such as β-thalassemia or sickle cell disease. A major limitation of current vectors is their inability to achieve efficient gene transfer into quiescent cells, such as human CD34+ cells that reside in the Go phase of the cell cycle and are highly enriched in hemopoietic stem cells. For that reason, le Read More