Nucleic acid delivery to differentiated retinal pigment epithelial cells using cell-penetrating peptide as a carrier.
Eur J Pharm Biopharm
; 140: 91-99, 2019 Jul.
Article
em En
| MEDLINE
| ID: mdl-31085311
ABSTRACT
Nucleic acid delivery to the eye is a promising treatment strategy for many retinal disorders. In this manuscript, retinal gene delivery with non-coated and chondroitin sulphate (CS) coated amphipathic and cationic peptides was tested. The transfection and gene knockdown efficiencies were evaluated in different retinal pigment epithelial (RPE) cell models including both dividing and differentiated cells. In addition, the mobility of peptide-based gene delivery systems 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 knockdown in dividing cells. We further demonstrate that incorporation of CS improves the efficiency of gene delivery of 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 delivery systems 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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MEDLINE
Assunto principal:
Retina
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Pigmentos da Retina
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Ácidos Nucleicos
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Diferenciação Celular
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Células Epiteliais
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Peptídeos Penetradores de Células
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article