Development and characterization of self-assembling nanoparticles using a bio-inspired amphipathic peptide for gene delivery
Abstract
The design of a non-viral gene delivery vehicle capable of delivering and releasing a functional nucleic acid cargo intracellularly remains a formidable challenge. For systemic gene therapy to be successful a delivery vehicle is required that protects the nucleic acid cargo from enzymatic degradation, extravasates from the vasculature, traverses the cell membrane, disrupts the endosomal vesicles and unloads the cargo at its destination site, namely the nucleus for the purposes of gene delivery. This manuscript reports the extensive investigation of a novel amphipathic peptide composed of repeating RALA units capable of overcoming the biological barriers to gene delivery both in vitro and in vivo. Our data demonstrates the spontaneous self-assembly of cationic DNA-loaded nanoparticles when the peptide is complexed with pDNA. Nanoparticles were <100nm, were stable in the presence of serum and were fusogenic in nature, with increased peptide α-helicity at a lower pH. Nanoparticles proved to be non-cytotoxic, readily traversed the plasma membrane of both cancer and fibroblast cell lines and elicited reporter-gene expression following intravenous delivery in vivo. The results of this study indicate that RALA presents an exciting delivery platform for the systemic delivery of nucleic acid therapeutics.
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Peptides can also be used for mRNA delivery.
“In addition to lipid and polymer carriers, peptides can also be used for mRNA delivery.331–333”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [332]
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Self-citation
- Authors
- McCarthy, H. O., McCaffrey, J., McCrudden, C. M., Zholobenko, A., Ali, A. A., McBride, J. W., Massey, A. S., Pentlavalli, S., Chen, K.-H., Cole, G., Loughran, S. P., Dunne, N. J., Donnelly, R. F., Kett, V. L., & Robson, T.
- Affiliations
- Queen's University Belfast (GB)
- Corresponding author
- McCarthy, Helen O.
- ORCID
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 189
- Pages
- 141-149
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2078413016
- Cited by
- 216
- References
- 37
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 15 · 2023: 20 · 2022: 29 · 2021: 16 · 2020: 27 · 2019: 23 · 2018: 16 · 2017: 14 · 2016: 12 · 2015: 15 · 2014: 3
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- The Royal Society (RG2010R2)
- Cancer Research UK (A13800, A14271)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- non-viral gene delivery, peptide amphiphiles, nanoparticle self-assembly, peptide-DNA complexes, endosomal escape, intravenous gene delivery, systemic gene therapy, pH-responsive peptides, nucleic acid therapeutics
- MeSH terms
- Animals, Cell Line, Circular Dichroism, DNA, Erythrocytes, Female, Hemolysis, Humans, Mice, Inbred C57BL, Particle Size, Peptides, Plasmids, Sheep, Gene Transfer Techniques, Cell Line, Tumor, Luciferases, Firefly, Nanoparticles
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