Nucleic acid delivery to differentiated retinal pigment epithelial cells using cell-penetrating peptide as a carrier
2019
Abstract Nucleic acid delivery to the eye is a promising treatment strategy for many retinal disorders. In this manuscript, retinal
gene deliverywith non-coated and
chondroitin sulphate(CS) coated amphipathic and cationic peptides was tested. The transfection and
gene knockdownefficiencies were evaluated in different
retinal pigmentepithelial (RPE) cell models including both dividing and differentiated cells. In addition, the mobility of peptide-based
gene deliverysystems was examined in porcine vitreous by particle tracking analysis. The results indicate that amphipathic and cationic peptides are safe in vitro and are capable of high transgene expression and
gene knockdownin
dividing cells. We further demonstrate that incorporation of CS improves the efficiency of
gene deliveryof peptide-based systems. Most importantly, the transgene expression mediated by both non-coated and CS coated peptides was high in differentiated as well as in human primary RPE cells which are typically difficult to transfect. Coating of peptide-based
gene deliverysystems with CS improved diffusion in the vitreous and enhanced the stability of the polyplexes. The results indicate that a peptide-based system can be fine-tuned as a promising approach for retinal
gene delivery.
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