---
title: "CCMV virus-like particles deliver DNA and RNA to fish cells in vitro and in vivo"
id: "biorxiv-5-cowpea-chlorotic-mottle-virus-virus-like-particles-as-dna-or-rna-delivery"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-5-cowpea-chlorotic-mottle-virus-virus-like-particles-as-dna-or-rna-delivery"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.15.759507v1?rss=1"
published_at: "2026-10-20T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CCMV virus-like particles deliver DNA and RNA to fish cells in vitro and in vivo
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-5-cowpea-chlorotic-mottle-virus-virus-like-particles-as-dna-or-rna-delivery
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.15.759507v1?rss=1)
- **Published At:** 2026-10-20T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators used **Cowpea Chlorotic Mottle Virus (CCMV)** capsid proteins to assemble empty virus-like particles (VLPs) and to encapsulate heterologous nucleic acids for delivery to fish cells. - The team packaged a 3,690 bp plasmid (pVax-GFP) and a 1,168 nt **GFP-mRNA** into VLPs; storage stability varied by payload and pH. - VLPs with pVax-GFP remained stable up to five weeks at pH 7.2 and pH 5. - VLPs containing GFP-mRNA were stable up to three weeks, but only at pH 4.5. - When added directly to culture medium, VLPs were internalized by fish and mammalian cell lines but did not release nucleic acids to permit reporter expression. - VLPs delivered to cells via chemical transfection did enable nucleic-acid transfer and subsequent reporter gene expression, according to the authors. - Co-administration with the cell-penetrating peptide **dfTAT** allowed only pVax-GFP VLPs (prepared at pH 7.2) to transfer DNA to mammalian cells; fish cells did not express the reporter under the same conditions. - In vivo intramuscular injection of pVax-GFP–containing VLPs into zebrafish larvae and juveniles produced plasmid transfer to myocytes with efficiency comparable to naked plasmid DNA injections, the authors reported. - The report is a preprint and has not undergone peer review. The article did not provide, in the abstract, quantitative transfection efficiencies, exact doses, concentrations, or full methodological parameters for many experiments; those details are not reported in the source abstract.
## Clinical Analysis & Structured Key Points
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G. Goldman, Shuqin Cao, Jeroen J. L. M. Cornelissen, Richard Kormelink, [ View ORCID Profile](http://orcid.org/0000-0001-9026-7320)Maria Forlenza doi: https://doi.org/10.64898/2026.10.15.759507 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Mark R. G. Goldman 1 Wageningen University and Research Wageningen Institute of Animal Sciences; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Mark%2B%2BR.%2BG.%2BGoldman%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Goldman%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMark%2B%2BR.%2BG.%2BGoldman%2B) * [ORCID record for Mark R. G. Goldman](http://orcid.org/0000-0003-0678-1023 "Open in new tab") Shuqin Cao 2 University of Twente; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Shuqin%2BCao%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Cao%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AShuqin%2BCao%2B) Jeroen J. L. M. Cornelissen 2 University of Twente; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jeroen%2B%2BJ.%2BL.%2BM.%2BCornelissen%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Cornelissen%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJeroen%2B%2BJ.%2BL.%2BM.%2BCornelissen%2B) Richard Kormelink 3 Wageningen University & Research; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Richard%2BKormelink%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Kormelink%20R&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ARichard%2BKormelink%2B) Maria Forlenza 4 The University of Edinburgh The Roslin Institute * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Maria%2BForlenza%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Forlenza%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMaria%2BForlenza%2B) * [ORCID record for Maria Forlenza](http://orcid.org/0000-0001-9026-7320 "Open in new tab") * For correspondence: mforlenz@ed.ac.uk * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.15.759507v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5885840/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.15.759507v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5885840/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.15.759507v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5885840/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.15.759507v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5885840/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Cowpea Chlorotic Mottle Virus (CCMV) is an icosahedral plant virus composed of 180 monomeric units of the capsid protein. Virions encapsulate the viral RNA genome, which can be removed from the virion by changing pH conditions, after which the capsid proteins can be reversibly assembled to form empty CCMV virus-like particles (VLPs), or VLPs that have encapsulated either heterologous DNA or RNA. Earlier research has shown that CCMV VLPs are suitable as delivery vehicles for heterologous DNA/RNA molecules into mammalian cells, leading to subsequent expression of their encoded genes. In this study, we evaluated the potential of CCMV VLPs to encapsulate nucleic acids and transfer them to fish cells in vitro, and to zebrafish larvae and juveniles in vivo. VLPs containing pVax-GFP plasmid (3690 bp) were stable for up to 5 weeks in buffer at pH 7.2 and pH 5, whereas VLPs containing GFP-mRNA (1168 nt) were stable for up to 3 weeks, but only when stored in a buffer at pH 4.5. When administered directly to the culture medium, VLPs were readily taken up by fish as well as mammalian cell lines but could not unpack and transfer nucleic acids to the cells. VLPs delivered by transfection however, could transfer nucleic acids to the cells, leading to reporter gene expression. When VLPs were administered directly to the culture medium along with the cell-penetrating peptide dfTAT, only VLPs containing pVax-GFP in pH 7.2 buffer were able to transfer DNA to mammalian but not fish cells. In vivo however, upon intramuscular injection, the same VLPs were able to transfer plasmid DNA to myocytes of zebrafish larvae and juveniles as efficiently as when injecting naked plasmid DNA. Altogether, these findings provide the foundation for future studies on the use of CCMV VLPs as delivery vehicles for DNA or RNA to fish cells. ### Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY 4.0 International license](http://creativecommons.org/licenses/by/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.15.759507v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/20/2026.10.15.759507.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Cowpea Chlorotic Mottle Virus virus-like particles as DNA or RNA delivery vehicle to fish cells Mark R. G. Goldman, Shuqin Cao, Jeroen J. L. M. Cornelissen, Richard Kormelink, Maria Forlenza bioRxiv 2026.10.15.759507; doi: https://doi.org/10.64898/2026.10.15.759507 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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