Rational design and characterisation of a linear cell penetrating peptide for non-viral gene delivery
| Autor: | Eoghan J. Mulholland, Monika Ziminska, Tracy Robson, Grace Cole, Vicky L. Kett, Helen O. McCarthy, Emma M. McErlean, Nicholas Dunne, Cian M. McCrudden, Niamh E. Buckley, John W. McBride, Stephen P. Loughran |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmaceutical Science
Peptide Cell-Penetrating Peptides 02 engineering and technology Gene delivery Transfection 03 medical and health sciences SDG 3 - Good Health and Well-being Non-viral Histidine Cell penetrating 030304 developmental biology chemistry.chemical_classification 0303 health sciences Chemistry Gene Transfer Techniques Rational design Genetic Therapy 021001 nanoscience & nanotechnology Amino acid Linear peptides Nucleic acids Biochemistry Nucleic acid Cell-penetrating peptide 0210 nano-technology Plasmids |
| Zdroj: | McErlean, E M, Ziminska, M, McCrudden, C M, McBride, J W, Loughran, S P, Cole, G, Mulholland, E J, Kett, V, Buckley, N E, Robson, T, Dunne, N J & McCarthy, H O 2020, ' Rational design and characterisation of a linear cell penetrating peptide for non-viral gene delivery ', Journal of Controlled Release, vol. 330, pp. 1288 . https://doi.org/10.1016/j.jconrel.2020.11.037 |
| ISSN: | 0168-3659 |
| Popis: | The design of a non-viral gene delivery system that can release a functional nucleic acid at the intracellular destination site is an exciting but also challenging proposition. The ideal gene delivery vector must be non-toxic, non-immunogenic, overcome extra- and intra-cellular barriers, protect the nucleic acid cargo from degradation with stability over a range of temperatures. A new 15 amino acid linear peptide termed CHAT was designed in this study with the goal of delivering DNA with high efficiency into cells in vitro and tissues in vivo. Rational design involved incorporation of key amino acids including arginine for nucleic acid complexation and cellular uptake, tryptophan to enhance hydrophobic interaction with cell membranes, histidine to facilitate endosomal escape and cysteine for stability and controlled cargo release. Six linear peptides were synthesised with strategic sequences and amino acid substitutions. Data demonstrated that all six peptides complexed pDNA to produce cationic nanoparticles less than 200 nm in diameter, but not all peptides resulted in successful transfection; indicating the influence of peptide design for endosomal escape. Peptide 4, now termed CHAT, was non-cytotoxic, traversed the plasma membrane of breast and prostate cancer cell lines, and elicited reporter-gene expression following intra-tumoural and intravenous delivery in vivo. CHAT presents an exciting new peptide for the delivery of nucleic acid therapeutics. |
| Databáze: | OpenAIRE |
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