ArticleMolecular therapy. Nucleic acids2021
Functionalized lipid nanoparticles for subcutaneous administration of mRNA to achieve systemic exposures of a therapeutic protein.
Article in Molecular therapy. Nucleic acids, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 86 citations in OpenAlex.
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- PEG-lipid shedding and biodistribution are shaped by nanocarrier morphology and lipid chemistry.Cell biomaterials · 2026Article
- Kinetically Controlled Assembly of Janus-Structured Nanobubble-Lipid Nanoparticles via Ultrasonic Micromixing.Chem & bio engineering · 2026Article
- CD39 mRNA therapy attenuates localized acute inflammation: A novel anti-inflammatory strategy using cationic nanoliposomes.Molecular therapy. Nucleic acids · 2026Article
- A Time-Resolved In Situ SAXS Method for Real-Time Monitoring of Lipid Nanoparticles Assembly.Membranes · 2026Article
- CAR-CD34 (+) hematopoietic stem/progenitor cells produced in vivo protect against thoracic aortic aneurysm and dissection.Nature communications · 2026Article
- Revolutionizing protein degradation: Harnessing nanoparticles for PROTAC delivery.Materials today. Bio · 2026Review
- Circular RNA encoding relaxin-2 as a potential therapy for liver fibrosis.Molecular therapy. Nucleic acids · 2026Article
- In vivo base editing gene therapy for heterozygous familial hypercholesterolemia: a phase 1 trial.Nature medicine · 2026Article
- Combining Anti-Inflammatory Drugs and Cell-Specific Expression-Suppression Reduces the Adjuvant Activity of mRNA-LNPs.Molecular pharmaceutics · 2026Article
- The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025Review
- Rational design of lipid nanoparticles for enabling gene therapies.Molecular therapy. Methods & clinical development · 2025Review
- Harnessing mRNA-lipid nanoparticles as innovative therapies for autoimmune diseases.Molecular therapy. Methods & clinical development · 2025Review
- The role of excipients in lipid nanoparticle metabolism: implications for enhanced therapeutic effect.Therapeutic delivery · 2025Review
- Using siRNA-Based Anti-Inflammatory Lipid Nanoparticles for Gene Regulation in Psoriasis.International journal of nanomedicine · 2025Article
- Research progress and strategy of FGF21 for skin wound healing.Frontiers in medicine · 2025Review
- The Function of the TGFβ Signaling Pathway in Connective Tissue Diseases: From Biology to Clinical Application.Journal of inflammation research · 2025Review
- Nucleic acid aptamers protect against lead (Pb(II)) toxicity.New biotechnology · 2024Article
- Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach.Journal of nanobiotechnology · 2024Review
- Current landscape of mRNA technologies and delivery systems for new modality therapeutics.Journal of biomedical science · 2024Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid nanoparticles (LNPs) are the most clinically advanced delivery system for RNA-based drugs but have predominantly been investigated for intravenous and intramuscular administration. Subcutaneous administration opens the possibility of patient self-administration and hence long-term chronic treatment that could enable messenger RNA (mRNA) to be used as a novel modality for protein replacement or regenerative therapies. In this study, we show that subcutaneous administration of mRNA formulated within LNPs can result in measurable plasma exposure of a secreted protein. However, subcutaneous administration of mRNA formulated within LNPs was observed to be associated with dose-limiting inflammatory responses. To overcome this limitation, we investigated the concept of incorporating aliphatic ester prodrugs of anti-inflammatory steroids within LNPs, i.e., functionalized LNPs to suppress the inflammatory response. We show that the effectiveness of this approach depends on the alkyl chain length of the ester prodrug, which determines its retention at the site of administration. An unexpected additional benefit to this approach is the prolongation observed in the duration of protein expression. Our results demonstrate that subcutaneous administration of mRNA formulated in functionalized LNPs is a viable approach to achieving systemic levels of therapeutic proteins, which has the added benefits of being amenable to self-administration when chronic treatment is required.
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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.