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  • Nawaz, MuhammadGothenburg University,Göteborgs universitet,Institutionen för medicin,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine,Institute of Medicine, Department of Rheumatology and Inflammation Research (författare)

Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for Their Functional Extensions

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • 2023-02-19
  • John Wiley & Sons,2023
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:his-22310
  • https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-22310URI
  • https://doi.org/10.1002/advs.202206187DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:151966489URI
  • https://gup.ub.gu.se/publication/324134URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • CC BY 4.0© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.E-mail: hadi.valadi@gu.seThe authors acknowledge the support from the National Genomics Infrastructure in Stockholm funded by Science for Life (SciLife) Laboratory, the Knut and Alice Wallenberg Foundation and the Swedish Research Council, and SNIC/Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure. Moreover, the authors acknowledge Mr. Mario Soriano Navarro at the Responsable Servicio Microscopía Electrónica, Valencia Spain, for technical assistance. This work was supported by grants from the Swedish Foundation of Strategic Research (Stiftelsen för strategisk forskning: SSF) in the Industrial Research Centre, FoRmulaEx - Nucleotide Functional Drug Delivery (Grant ID: IRC15-0065), the Swedish research council (VR, Grant ID: 2020-01316), and the Swedish governmental agency for innovation systems (VINNOVA, Grant ID: 2017-02960). This research was also funded by the Systems Biology Research Centre at the University of Skövde under grants from the Knowledge Foundation (Grant ID: 20160330).
  • Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells’ own vehicles called extracellular vesicles (EVs). The results show that cellular uptake of LNPs and their mRNA molecules occurs quickly, and that the translation of exogenously delivered mRNA begins immediately. Following the VEGF-A mRNA delivery to cells via LNPs, a fraction of internalized VEGF-A mRNA is secreted via EVs. The overexpressed VEGF-A mRNA is detected in EVs secreted from three different cell types. Additionally, RNA-Seq analysis reveals that as cells’ response to LNP-VEGF-A mRNA treatment, several overexpressed proangiogenic transcripts are packaged into EVs. EVs are further deployed to deliver VEGF-A mRNA in vitro and in vivo. Upon equal amount of VEGF-A mRNA delivery via three EV types or LNPs in vitro, EVs from cardiac progenitor cells are the most efficient in promoting angiogenesis per amount of VEGF-A protein produced. Intravenous administration of luciferase mRNA shows that EVs could distribute translatable mRNA to different organs with the highest amounts of luciferase detected in the liver. Direct injections of VEGF-A mRNA (via EVs or LNPs) into mice heart result in locally produced VEGF-A protein without spillover to liver and circulation. In addition, EVs from cardiac progenitor cells cause minimal production of inflammatory cytokines in cardiac tissue compared with all other treatment types. Collectively, the data demonstrate that LNPs transform EVs as functional extensions to distribute therapeutic mRNA between cells, where EVs deliver this mRNA differently than LNPs. 

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Heydarkhan-Hagvall, SepidehHögskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,BioPharmaceuticals R&D, Early Cardiovascular, Renal and Metabolism (CVRM), Bioscience Cardiovascular, AstraZeneca, Gothenburg, Mölndal, Sweden,Translationell Bioinformatik, Translational Bioinformatics(Swepub:his)heys (författare)
  • Tangruksa, BenyapaGothenburg University,Göteborgs universitet,Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden,Translationell Bioinformatik, Translational Bioinformatics,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xtangb (författare)
  • González-King Garibotti, HernánBioPharmaceuticals R&D, Early Cardiovascular, Renal and Metabolism (CVRM), Bioscience Cardiovascular, AstraZeneca, Gothenburg, Mölndal, Sweden (författare)
  • Jing, YujiaAdvanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Mölndal, Sweden (författare)
  • Marco, Maugeri,1983Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xmauma (författare)
  • Kohl, FranziskaKarolinska Institutet,BioPharmaceuticals R&D, Discovery Sciences, Translational Genomics, AstraZeneca, Gothenburg, Mölndal, Sweden ; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Solna, Sweden (författare)
  • Hultin, LeifBioPharmaceuticals R&D, Clinical Pharmacology and Safety Science, Imaging and Data Analytics, AstraZeneca, Gothenburg, Mölndal, Sweden (författare)
  • Reyahi, AzadehGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xreyaz (författare)
  • Camponeschi, AlessandroGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xcampa (författare)
  • Kull, BengtBioPharmaceuticals R&D, Early Cardiovascular, Renal and Metabolism (CVRM), Bioscience Cardiovascular, AstraZeneca, Gothenburg, Mölndal, Sweden (författare)
  • Christoffersson, Jonas,1986-Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,BioPharmaceuticals R&D, Early Cardiovascular, Renal and Metabolism (CVRM), Bioscience Cardiovascular, AstraZeneca, Gothenburg, Mölndal, Sweden,Translationell Bioinformatik, Translational Bioinformatics(Swepub:his)chrj (författare)
  • Grimsholm, Ola,1979Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xgriol (författare)
  • Jennbacken, KarinBioPharmaceuticals R&D, Early Cardiovascular, Renal and Metabolism (CVRM), Bioscience Cardiovascular, AstraZeneca, Gothenburg, Mölndal, Sweden (författare)
  • Sundqvist, MartinaGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xsundq (författare)
  • Wiseman, JohnBioPharmaceuticals R&D, Discovery Sciences, Translational Genomics, AstraZeneca, Gothenburg, Mölndal, Sweden (författare)
  • Bidar, Abdel WahadBioPharmaceuticals R&D, Discovery Sciences, Translational Genomics, AstraZeneca, Gothenburg, Mölndal, Sweden (författare)
  • Lindfors, Lennart,1961Advanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Mölndal, Sweden(Swepub:gu)xllend (författare)
  • Synnergren, JaneGothenburg University,Göteborgs universitet,Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden,Translationell Bioinformatik, Translational Bioinformatics,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xsynja (författare)
  • Valadi, Hadi,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xvalha (författare)
  • Göteborgs universitetInstitutionen för medicin (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Advanced Science: John Wiley & Sons10:122198-3844

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