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Plasmid DNA delivery by arginine-rich cell-penetrating peptides containing unnatural amino acids
Affiliation:1. Institute of Biomedicine and Translational Medicine, University of Tartu, Estonia;2. Institute of Molecular and Cell Biology, University of Tartu, Estonia;3. Institute of Technology, University of Tartu, Estonia;4. Department of Dermatology and Venereology, University of Tartu, Tartu, Estonia;5. Dermatology Clinic, Tartu University Hospital, Tartu, Estonia;6. Department of Medicine, Vanderbilt University Medical Center, United States;7. Department of Neurochemistry, Stockholm University, Sweden;8. Department of Bioscience, Karolinska Institute, Sweden
Abstract:
Cell-penetrating peptides (CPPs) have been developed as drug, protein, and gene delivery tools. In the present study, arginine (Arg)-rich CPPs containing unnatural amino acids were designed to deliver plasmid DNA (pDNA). The transfection ability of one of the Arg-rich CPPs examined here was more effective than that of the Arg nonapeptide, which is the most frequently used CPP. The transfection efficiencies of Arg-rich CPPs increased with longer post-incubation times and were significantly higher at 48-h and 72-h post-incubation than that of the commercially available transfection reagent TurboFect. These Arg-rich CPPs were complexed with pDNA for a long time in cells and effectively escaped from the late endosomes/lysosomes into the cytoplasm. These results will be helpful for designing novel CPPs for pDNA delivery.
Keywords:Cell-penetrating peptide  Arginine  Gene transfer  Unnatural amino acid  Plasmid DNA delivery
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