ArticleBioengineering & translational medicine2023
Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety.
Article in Bioengineering & translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Overcoming hepatic tropism: Precision engineering of lipid nanoparticles for extrahepatic RNA delivery.Materials today. Bio · 2026Review
- Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.Nature nanotechnology · 2026Article
- Bridging the Lab-to-Clinic Gap in Intranasal Nanomaterial-Based Chemotherapy for Glioblastoma.Pharmaceutics · 2026Review
- Deciphering the biological fate of mRNA-LNP-based biologics: A perspective from tissue to intracellular distribution.Acta pharmaceutica Sinica. B · 2026Review
- Rational design and applications of piperazine and cyclohexane ionizable lipids for PKU and SSADH deficiency.Molecular therapy. Nucleic acids · 2025Article
- The impact of chemical reactivity on the quality and stability of RNA-LNP pharmaceuticals.Nature reviews. Chemistry · 2025Review
- Hydrophilic α-Aryl-α-Diazoamides for Protein Esterification.Synlett : accounts and rapid communications in synthetic organic chemistry · 2025Article
- Probing the Role of Lipid Nanoparticle Elasticity on mRNA Delivery to the Placenta.Nano letters · 2025Article
- Rational Design of Lipid Nanoparticles for Enhanced mRNA Vaccine Delivery via Machine Learning.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Noncoding RNA Lipotherapeutics: A Promising Breakthrough in Pulmonary Hypertension Treatment.Current pharmaceutical biotechnology · 2025Review
- Advances and prospects of RNA delivery nanoplatforms for cancer therapy.Acta pharmaceutica Sinica. B · 2025Review
- Discovery and development of a safe and efficient COVID-19 mRNA vaccine, STP2104, using a novel capping library screening method.Frontiers in immunology · 2025Article
- Discovery of peptides for ligand-mediated delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia.Molecular therapy. Nucleic acids · 2024Article
- Article
- Overcoming thermostability challenges in mRNA-lipid nanoparticle systems with piperidine-based ionizable lipids.Communications biology · 2024Article
- Emerging delivery approaches for targeted pulmonary fibrosis treatment.Advanced drug delivery reviews · 2024Review
- Composition of lipid nanoparticles for targeted delivery: application to mRNA therapeutics.Frontiers in pharmacology · 2024Review
- Development of Lipid Nanoparticle Formulation for the Repeated Administration of mRNA Therapeutics.Biomaterials research · 2024Article
- Article
- Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety.Bioengineering & translational medicine · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mRNA-based protein replacement therapy has received much attention as a novel intervention in clinical disease treatment. Lipid nanoparticles (LNPs) are widely used for their therapeutic potential to efficiently deliver mRNA. However, clinical translation has been hampered by the immunogenicity of LNPs that may aggravate underlying disease states. Here, we report a novel ionizable LNP with enhanced potency and safety. The piperazine-based biodegradable ionizable lipid (244cis) was developed for LNP formulation and its level of protein expression and immunogenicity in the target tissue was evaluated. It was found that 244cis LNP enabled substantial expression of the target protein (human erythropoietin), while it minimally induced the secretion of monocyte chemoattractant protein 1 (MCP-1) as compared to other conventional LNPs. Selective lung targeting of 244cis LNP was further investigated in tdTomato transgenic mice with bleomycin-induced pulmonary fibrosis (PF). The repeated administration of 244cis LNP with Cre recombinase mRNA achieved complete transfection of lung endothelial cells (~80%) and over 40% transfection of Sca-1-positive fibroblasts. It was shown that 244cis LNP allows the repeated dose of mRNA without the loss of activity due to its low immunogenicity. Our results demonstrate that 244cis LNP has great potential for the treatment of chronic diseases in the lungs with improved potency and safety.
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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.