Extracellular Vesicles - Roles in mRNA-Based Therapies
| dc.contributor.author | Tangruksa, Benyapa | |
| dc.date.accessioned | 2025-05-20T07:25:48Z | |
| dc.date.available | 2025-05-20T07:25:48Z | |
| dc.date.issued | 2025-05-20 | |
| dc.description.abstract | Efficient and targeted delivery of therapeutic mRNA remains a major challenge in RNA-based medicine. This thesis explores how lipid nanoparticles (LNPs) and extracellular vesicles (EVs) cooperate in the delivery and redistribution of vascular endothelial growth factor A (VEGFA) mRNA, therapeutic mRNA that induces blood vessel formation and holds strong potential for treating cardiovascular diseases through regenerative angiogenesis. Paper I demonstrates that LNPs efficiently deliver VEGFA mRNA to human cells, leading to rapid uptake and translation. A portion of the internalized mRNA is subsequently secreted within EVs, which also acquire enriched proangiogenic transcripts. Among tested EVs, those derived from cardiac progenitor cells (CPC-EVs) showed superior angiogenic potential and minimal inflammatory response. In Paper II, biodistribution studies in mice revealed that CPC-EVs outperformed LNPs and non-cardiac EVs in delivering VEGFA mRNA to heart tissue, with reduced liver accumulation. CPC-EVs induced local protein expression and minimal transcriptomic disruption, highlighting their tissue-targeting advantage and safety. Paper III investigates how LNP treatment alters EV transcriptomes and how these modified EVs affect recipient tissues. VEGFA mRNA was the most enriched transcript across all EV types. CPC-EVs upregulated VEGFR-1 and VEGFR-2 specifically in cardiac tissue. Further analysis revealed that human mRNA transcripts were detectable in recipient mouse hearts. In summary, this thesis explores the interplay between LNPs and EVs in transporting VEGFA mRNA for therapeutic angiogenesis. LNPs enable efficient cellular uptake and subsequently trigger re-packaging of mRNA into EVs. CPC-EVs showed superior heart targeting and angiogenic potential with low inflammation. The findings highlight a promising strategy for regenerative treatment of cardiovascular diseases. | sv |
| dc.gup.defencedate | 2025-06-12 | |
| dc.gup.defenceplace | Torsdagen den 12 juni 2025, kl. 13.00, Föreläsningssalen våning 3, Guldhedsgatan 10A, Göteborg | sv |
| dc.gup.department | Institute of Medicine. Department of Rheumatology and Inflammation Research | sv |
| dc.gup.dissdb-fakultet | SA | |
| dc.gup.origin | University of Gothenburg. Sahlgrenska Academy | sv |
| dc.identifier.isbn | 978-91-8115-262-3 (PRINT) | |
| dc.identifier.isbn | 978-91-8115-263-0 (PDF) | |
| dc.identifier.uri | https://hdl.handle.net/2077/85349 | |
| dc.language.iso | eng | sv |
| dc.relation.haspart | I. Lipid nanoparticles deliver the therapeutic VEGFA mRNA in vitro and in vivo and transform extracellular vesicles for their functional extensions. Nawaz, M., Heydarkhan‐Hagvall, S., Tangruksa, B., González‐King Garibotti, H., Jing, Y., Maugeri, M., Kohl, F., Hultin, L., Reyahi, A., Camponeschi, A., Kull, B., Christoffersson, J., Grimsholm, O., Jennbacken, K., Sundqvist, M., Wiseman, J., Bidar, A. W., Lindfors, L., Synnergren, J., & Valadi, H. Advanced Science. 2023 Apr;10(12):2206187. https://doi.org/10.1002/advs.202206187 | sv |
| dc.relation.haspart | II. Targeted delivery of mRNA to the heart via extracellular vesicles or lipid nanoparticles. Nawaz, M., Tangruksa, B., Heydarkhan‐Hagvall, S., Kohl, F., González‐King Garibotti, H., Jing, Y., Payandeh, Z., Reyahi, A., Jennbacken, K., Wiseman, J., Hultin, L., Lindfors, L., Synnergren, J., & Valadi, H. BioRxiv. 2025:2025-01. https://doi.org/10.1101/2025.01.25.634881 | sv |
| dc.relation.haspart | III. Transcriptomic characterization of extracellular vesicles (EVs) and the tissue response following VEGFA mRNA delivery via EVs. Tangruksa, B., Nawaz, M., Heydarkhan‐Hagvall, S., Jin, T., Wiseman, J., Lindfors, L., Synnergren, J., & Valadi, H. Manuscript | sv |
| dc.subject | mRNA therapeutics | sv |
| dc.subject | extracellular vesicles | sv |
| dc.subject | lipid nanoparticles | sv |
| dc.subject | exosomes | sv |
| dc.subject | VEGFA | sv |
| dc.subject | VEGF receptors | sv |
| dc.subject | targeted delivery | sv |
| dc.subject | angiogenesis | sv |
| dc.subject | cardiac progenitor cells | sv |
| dc.subject | transcriptomics | sv |
| dc.subject | RNA sequencing | sv |
| dc.subject | regenerative medicine | sv |
| dc.title | Extracellular Vesicles - Roles in mRNA-Based Therapies | sv |
| dc.type | text | eng |
| dc.type.degree | Doctor of Philosophy (Medicine) | sv |
| dc.type.svep | Doctoral thesis | eng |
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