PMC:2669177 / 26269-27820
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/2669177","sourcedb":"PMC","sourceid":"2669177","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2669177","text":"Viral gene therapy has been remarkably successful in treating some types of ocular diseases, the most notable example of which to date being the AAV-mediated long-term rescue of vision in Briard dogs harboring a mutation in RPE65 [1], [2]. Results from these studies have prompted three successful and ongoing human clinical trials [42]–[44]. However, the development of effective non-viral vectors is a prudent step as an alternative to more traditional methods. While a number of non-viral approaches have been explored, including the use of liposomes, electroporation of naked DNA, and gene delivery with dendrimers, they have encountered persistent problems with limited uptake and short-term gene expression [6], although advances in this area have been made [45]. Therefore, we chose to test the efficacy of compacted DNA nanoparticles comprised of PEG-substituted lysine peptides for gene delivery. We show here that these nanoparticles represent a significant improvement over other non-viral vectors in terms of transgene uptake and stability of expression (elevated levels detected to the latest timepoint examined PI-120). Furthermore, we show partial morphological and functional rescue of the rds +/− model. Because of the structural defects that accompany Rds mutations or deficiency, rescue of the disease phenotype heretofore has been particularly difficult [29]–[31]. However, since most Rds-associated RP in humans is due to loss-of-function mutations causing a haploinsufficiency phenotype, the rds+/− is a relevant model to 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