Combined biolistic and cell penetrating peptide delivery for the development of scalable intradermal DNA vaccines

So, Roizza Beth; Li, Gang; Brentville, Victoria; Daly, Janet M; Dixon, James E

Abstract

Physical-based gene delivery via biolistic methods (such as the Helios gene gun) involve precipitation of nucleic acids onto microparticles and direct transfection through cell membranes of exposed tissue (e.g. skin) by high velocity acceleration. The glycosaminoglycan (GAG)-binding enhanced transduction (GET) system exploits novel fusion peptides consisting of cell-binding, nucleic acid condensing, and cell-penetrating domains, which enable enhanced transfection across multiple cell types. In this study, we combined chemical (GET) and physical (gene gun) DNA delivery systems, and hypothesized the combination would generate enhanced distribution and effective uptake in cells not initially transfected by biolistic penetration. Physicochemical characterization, optimization of bullet contents and transfection experiments in vitro in cell monolayers and engineered tissue demonstrated these formulations transfected efficiently, including DC2.4 dendritic cells. We incorporated these formulations into a biolistic format for gene gun by forming fireable dry bullets obtained via lyophilization (freeze drying). This system is simple and with enhanced scalability compared to conventional methods to generate bullets. Flushed GET bullet contents retained their ability to mediate transfection (17-fold greater and 13-fold greater reporter gene expression than standard spermidine bullets in the absence and presence of serum, respectively). Fired GET bullets in vitro (in cells and collagen gels) and in vivo (mice) showed increased reporter gene transfection compared to untreated controls, whilst maintaining cell viability in vitro and having no obvious toxicity in vivo. Lastly, a SARS-CoV-2 plasmid DNA vaccine with spike (S) protein-receptor binding domain (S-RBD) was delivered by gene gun using GET bullets. Specific T cell and antibody responses comparable to the conventional system were generated. The non-physical and physical combination of GET‑gold-DNA carriers using gene gun shows potential as an alternative DNA delivery method that is scalable for mass deployable vaccination and intradermal gene delivery.

Citation

So, R. B., Li, G., Brentville, V., Daly, J. M., & Dixon, J. E. (2024). Combined biolistic and cell penetrating peptide delivery for the development of scalable intradermal DNA vaccines. Journal of Controlled Release, 367, 209-222. https://doi.org/10.1016/j.jconrel.2024.01.031

• Journal Article Type: Article
• Acceptance Date: Jan 15, 2024
• Online Publication Date: Jan 25, 2024
• Publication Date: 2024-03
• Deposit Date: Jan 18, 2024
• Publicly Available Date: Feb 5, 2024
• Journal: Journal of Controlled Release
• Print ISSN: 0168-3659
• Electronic ISSN: 1873-4995
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 367
• Pages: 209-222
• DOI: https://doi.org/10.1016/j.jconrel.2024.01.031
• Keywords: Gene gun, GAG-binding enhanced transduction (GET), Cell penetrating peptide (CPP), Gene delivery, DNA vaccine, SARS-CoV-2
• Public URL: https://nottingham-repository.worktribe.com/output/29837733
• Additional Information: This article is maintained by: Elsevier; Article Title: Combined biolistic and cell penetrating peptide delivery for the development of scalable intradermal DNA vaccines; Journal Title: Journal of Controlled Release; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jconrel.2024.01.031; Content Type: article; Copyright: © 2024 The Authors. Published by Elsevier B.V.