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Published on: February 1, 2019
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Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for
Muhammad Nawaz1, Sepideh Heydarkhan-Hagvall2,3, Benyapa Tangruksa1,3
1Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41346, Sweden.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 22, 2023
Summary
Lipid nanoparticles deliver messenger RNA (mRNA) for new blood vessel growth. Extracellular vesicles then extend this mRNA delivery between cells, offering a novel therapeutic approach for cardiovascular diseases.
Area of Science:
- Biotechnology
- Molecular Biology
- Cardiovascular Research
Background:
- Lipid nanoparticles (LNPs) are established mRNA delivery vehicles, notably in COVID-19 vaccines.
- Therapeutic mRNA delivery for angiogenesis, like VEGF-A mRNA, is a promising strategy for cardiovascular diseases.
- Extracellular vesicles (EVs) are cellular vehicles involved in intercellular communication.
Purpose of the Study:
- To investigate the delivery of VEGF-A mRNA using LNPs and its subsequent intercellular transport via EVs.
- To quantify LNP and mRNA uptake kinetics and analyze the role of EVs in extending mRNA distribution.
- To evaluate the therapeutic potential of EV-mediated mRNA delivery for angiogenesis in vitro and in vivo.
Main Methods:
- Delivery of VEGF-A mRNA using LNPs to various cell types.
- Stoichiometric quantification of LNP and mRNA uptake and secretion via EVs.
- RNA-sequencing to identify proangiogenic transcripts packaged into EVs.
- In vitro and in vivo studies assessing angiogenesis, biodistribution, and inflammatory responses.
Main Results:
- Rapid cellular uptake of LNPs and immediate translation of delivered mRNA.
- Secretion of internalized VEGF-A mRNA via EVs, with detection in multiple cell types.
- EVs, particularly those from cardiac progenitor cells, efficiently delivered mRNA and promoted angiogenesis.
- EVs facilitated mRNA distribution to various organs in vivo, with preferential liver uptake.
- Direct cardiac injection of mRNA via EVs or LNPs resulted in localized VEGF-A production with minimal inflammation.
Conclusions:
- LNPs can facilitate the transfer of therapeutic mRNA to EVs, extending its intercellular distribution.
- EVs serve as functional extensions for LNP-mediated mRNA delivery, offering distinct transport mechanisms.
- EV-mediated delivery of VEGF-A mRNA shows therapeutic potential for angiogenesis in cardiovascular disease models.
