ArticleMolecular therapy. Nucleic acids2019
Expression Kinetics and Innate Immune Response after Electroporation and LNP-Mediated Delivery of a Self-Amplifying mRNA in the Skin.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 81 citations in OpenAlex.
- A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Trial
- Influence of the administration route and dose on the expression and antibody responses of a reporter and avian influenza self-amplifying mRNA vaccine in poultry.The veterinary quarterly · 2026Article
- Enhanced antitumor immunity of mRNA vaccines by bioorthogonal-like delayed activation of exogeneous STING.Nature biotechnology · 2026Article
- Biomaterial-Integrated Electroporation for Therapeutic Delivery: From Gene Editing to Tumor Ablation and Immune Modulation.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Towards controllable self-amplifying RNA.Nature biomedical engineering · 2026Article
- Optimizing C14120-based LNPs forMolecular therapy. Nucleic acids · 2026Article
- Single intramuscular injection of self-amplifying RNA ofScience (New York, N.Y.) · 2026Article
- Biologics for bone regeneration: advances in cell, protein, gene, and mRNA therapies.Bone research · 2026Review
- Low-cost, handheld, multi-pulse electroporators for simplified nucleic acid delivery in skin.Bioengineering & translational medicine · 2026Article
- Divergent Delivery and Expression Kinetics of Lipid and Polymeric Nanoparticles across mRNA Modalities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency.Nature biotechnology · 2025Article
- Unleashing the potential of mRNA: Overcoming delivery challenges with nanoparticles.Bioengineering & translational medicine · 2025Review
- Realizing time-staggered expression of nucleic acid-encoded proteins by co-delivery of messenger RNA and plasmid DNA on a single nanocarrier.Drug delivery and translational research · 2024Article
- Advanced technologies for the development of infectious disease vaccines.Nature reviews. Drug discovery · 2024Review
- Review
- Strategies to reduce the risks of mRNA drug and vaccine toxicity.Nature reviews. Drug discovery · 2024Review
- Review
- Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity.Vaccines · 2024Review
- Composition of lipid nanoparticles for targeted delivery: application to mRNA therapeutics.Frontiers in pharmacology · 2024Review
- Development of novel SARS-CoV-2 viral vectors.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this work, we studied the expression kinetics and innate immune response of a self-amplifying mRNA (sa-RNA) after electroporation and lipid-nanoparticle (LNP)-mediated delivery in the skin of mice. Intradermal electroporation of the sa-RNA resulted in a plateau-shaped expression, with the plateau between day 3 and day 10. The overall protein expression of sa-RNA was significantly higher than that obtained after electroporation of plasmid DNA (pDNA) or non-replication mRNAs. Moreover, using IFN-β reporter mice, we elucidated that intradermal electroporation of sa-RNA induced a short-lived moderate innate immune response, which did not affect the expression of the sa-RNA. A completely different expression profile and innate immune response were observed when LNPs were used. The expression peaked 24 h after intradermal injection of sa-RNA-LNPs and subsequently showed a sharp drop. This drop might be explained by a translational blockage caused by the strong innate immune response that we observed in IFN-β reporter mice shortly (4 h) after intradermal injection of sa-RNA-LNPs. A final interesting observation was the capacity of sa-RNA-LNPs to transfect the draining lymph nodes after intradermal injection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.