Nucleic acid delivery to differentiated retinal pigment epithelial cells using cell-penetrating peptide as a carrier

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  • Bano Subia, University of Eastern Finland
  • ,
  • Mika Reinisalo, University of Eastern Finland
  • ,
  • Namit Dey, Delhi Technological University
  • ,
  • Shirin Tavakoli, Helsingin yliopisto
  • ,
  • Astrid Subrizi, University of Eastern Finland
  • ,
  • Munia Ganguli, CSIR-Institute of Genomics and Integrative Biology
  • ,
  • Marika Ruponen, University of Eastern Finland

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.

Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume140
Pages (from-to)91-99
Number of pages9
ISSN0939-6411
DOIs
Publication statusPublished - 2019

    Research areas

  • Chondroitin sulphate, Gene delivery, Peptide carrier, Polyplexe, Retinal cell line

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