ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
In vivo mRNA expression of a multi-mechanistic mAb combination protects against Staphylococcus aureus infection.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Advancements of mRNA-lipid nanoparticle links to gene editing and immune responses.Journal, genetic engineering & biotechnology · 2026Review
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Human antibodies as emerging drugs for antimicrobial resistance.Trends in immunology · 2026Review
- Fc-free single-chain antibody mRNA therapy for airway infection of multidrug-resistant Pseudomonas aeruginosa.Nature communications · 2026Article
- Adeno-associated virus delivery of anti-alpha toxin monoclonal antibodies confers protection against Staphylococcus aureus infections.PLoS pathogens · 2026Article
- Low effectiveness of influenza vaccines vis-à-vis mechanism of protection by vaccines - potential causes and recommendations to improve control of influenza.Frontiers in immunology · 2026Review
- Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Nanoparticle-formulated mRNA encoding engineered multivalent SIRPα-Fc fusion proteins shows robust anti-cancer activity in preclinical models.Molecular therapy. Nucleic acids · 2025Article
- Broadly neutralizing monoclonal antibodies against influenza A viruses: current insights and future directions.Frontiers in microbiology · 2025Review
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Authors and funding
17 authors.
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Abstract
Single monoclonal antibodies (mAbs) can be expressed in vivo through gene delivery of their mRNA formulated with lipid nanoparticles (LNPs). However, delivery of a mAb combination could be challenging due to the risk of heavy and light variable chain mispairing. We evaluated the pharmacokinetics of a three mAb combination against Staphylococcus aureus first in single chain variable fragment scFv-Fc and then in immunoglobulin G 1 (IgG1) format in mice. Intravenous delivery of each mRNA/LNP or the trio (1 mg/kg each) induced functional antibody expression after 24 h (10-100 μg/mL) with 64%-78% cognate-chain paired IgG expression after 3 days, and an absence of non-cognate chain pairing for scFv-Fc. We did not observe reduced neutralizing activity for each mAb compared with the level of expression of chain-paired mAbs. Delivery of the trio mRNA protected mice in an S. aureus-induced dermonecrosis model. Intravenous administration of the three mRNA in non-human primates achieved peak serum IgG levels ranging between 2.9 and 13.7 μg/mL with a half-life of 11.8-15.4 days. These results suggest nucleic acid delivery of mAb combinations holds promise and may be a viable option to streamline the development of therapeutic antibodies.
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