{"entity": "publication", "iuid": "b033fd02ecbb49fabd7e523c90011c8f", "timestamp": "2026-10-19T22:58:31.076Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b033fd02ecbb49fabd7e523c90011c8f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b033fd02ecbb49fabd7e523c90011c8f"}}, "title": "Targeted Delivery of mRNA to the Heart via Extracellular Vesicles or Lipid Nanoparticles.", "authors": [{"family": "Nawaz", "given": "Muhammad", "initials": "M", "orcid": "0000-0002-0792-8296", "researcher": {"href": "https://publications.scilifelab.se/researcher/70ab4033bb6a44d1b9bd1f29f521bde3.json"}}, {"family": "Tangruksa", "given": "Benyapa", "initials": "B"}, {"family": "Heydarkhan-Hagvall", "given": "Sepideh", "initials": "S"}, {"family": "Kohl", "given": "Franziska", "initials": "F"}, {"family": "Garibotti", "given": "Hern\u00e1n Gonz\u00e1lez-King", "initials": "HG", "orcid": "0000-0003-4344-9484", "researcher": {"href": "https://publications.scilifelab.se/researcher/58cbb7a64622479f97f2df3e955bed91.json"}}, {"family": "Jing", "given": "Yujia", "initials": "Y"}, {"family": "Payandeh", "given": "Zahra", "initials": "Z"}, {"family": "Reyahi", "given": "Azadeh", "initials": "A"}, {"family": "Jennbacken", "given": "Karin", "initials": "K"}, {"family": "Wiseman", "given": "John", "initials": "J"}, {"family": "Hultin", "given": "Leif", "initials": "L"}, {"family": "Lindfors", "given": "Lennart", "initials": "L"}, {"family": "Synnergren", "given": "Jane", "initials": "J"}, {"family": "Valadi", "given": "Hadi", "initials": "H", "orcid": "0000-0003-3482-2451", "researcher": {"href": "https://publications.scilifelab.se/researcher/630e0bcbae2f42b8bf7e6185c306b607.json"}}], "type": "journal article", "published": "2026-06-00", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "15", "issue": "6", "pages": "e70324", "issn-l": "2001-3078"}, "abstract": "Efficient and specific delivery of mRNA to target tissues is critical for maximising therapeutic benefits while minimising off-target effects and systemic toxicity. Systemic administration of mRNA using lipid nanoparticles (LNPs) or extracellular vesicles (EVs) typically leads to predominant accumulation in the liver. We hypothesised that cardiac-specific EVs could promote enhanced relative cardiac enrichment of delivered mRNA compared with non-cardiac EVs or LNPs. In mice, intravenous administration of cardiac progenitor cell-derived EVs (CPC-EVs) achieved the greatest relative cardiac selectivity of modified mRNA encoding vascular endothelial growth factor A (VEGF-A) to the heart, with reduced liver accumulation relative to non-cardiac EVs and LNPs. Cytokine profiling across seven organs revealed that LNP delivery triggered a widespread pro-inflammatory response, whereas CPC-EVs elicited only a localised and limited cytokine activation, suggesting a more favourable safety profile. Furthermore, direct intramyocardial injection of CPC-EVs not only led to efficient mRNA uptake by cardiac tissue and robust VEGF-A protein expression, but also minimal transcriptomic perturbation in the cardiac tissue, as confirmed by RNA-seq. In contrast, LNPs and non-cardiac EVs induced widespread perturbation in the transcriptome of cardiac tissue. Functionally, VEGF-A mRNA delivery via CPC-EVs markedly increased CD31 and \u03b1-SMA expression and vessel formation in ex vivo aortic ring assays, confirming enhanced angiogenic potential. Together, these findings support CPC-EVs as a promising platform for achieving enhanced cardiac delivery of mRNA, with reduced liver accumulation, limited off-target transcriptomic perturbation, a more selective cytokine response, and enhanced angiogenic activity in ex vivo assays.", "doi": "10.1002/jev2.70324", "pmid": "42275464", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13257898"}], "notes": [], "created": "2026-10-14T12:53:54.744Z", "modified": "2026-10-14T12:53:54.899Z"}