ArticleScientific reports2020
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- PEG-associated efficacy loss in lipid nanoparticles persists across formulation modifications for mRNA delivery.Drug delivery and translational research · 2026Article
- Engineering mRNA-LNP Medicines for the Ageing Brain: Opportunities and Challenges for Neurodegenerative Diseases.Exploration (Beijing, China) · 2026Review
- mRNA Therapeutics Beyond Infectious Diseases: Expanding Therapeutic Applications and Future Perspectives.Immunity, inflammation and disease · 2026Review
- PEG-associated efficacy loss in lipid nanoparticles persists across formulation modifications for mRNA delivery.Research square · 2026Article
- mRNA Lipid Nanoparticles for Cell Engineering in Vivo and in Vitro: Current Applications and Future Directions.MedComm · 2026Review
- Dual SORT LNPs for multi-organ base editing.Nature biotechnology · 2026Article
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Messenger RNA therapy in bone and joint diseases: Rationale, delivery systems, and applications.Biomaterials translational · 2026Article
- Nanoparticle delivery of VEGF-B mRNA promotes T cell infiltration within tumor and triggers robust antitumor immunity.Molecular therapy. Nucleic acids · 2025Article
- Delivering the Message: Translating mRNA Therapy for Liver Inherited Metabolic Diseases.Journal of inherited metabolic disease · 2025Review
- Review
- Serum factors create species-specific barriers to hepatic gene transfer by lipid nanoparticles in liver-humanized mice.Molecular therapy. Methods & clinical development · 2025Article
- Advancements and challenges in mRNA and ribonucleoprotein-based therapies: From delivery systems to clinical applications.Molecular therapy. Nucleic acids · 2024Review
- Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders.Acta pharmaceutica Sinica. B · 2024Review
- Frameworks for transformational breakthroughs in RNA-based medicines.Nature reviews. Drug discovery · 2024Review
- A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach.International journal of biological sciences · 2024Review
- Induction of long-term tolerance to a specific antigen using anti-CD3 lipid nanoparticles following gene therapy.Molecular therapy. Nucleic acids · 2023Article
- Article
- Unlocking the promise of mRNA therapeutics.Nature biotechnology · 2022Review
- Self-Amplifying RNA Approach for Protein Replacement Therapy.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alpha 1-antitrypsin (AAT) deficiency arises from an inherited mutation in the SERPINA1 gene. The disease causes damage in the liver where the majority of the AAT protein is produced. Lack of functioning circulating AAT protein also causes uninhibited elastolytic activity in the lungs leading to AAT deficiency-related emphysema. The only therapy apart from liver transplantation is augmentation with human AAT protein pooled from sera, which is only reserved for patients with advanced lung disease caused by severe AAT deficiency. We tested modified mRNA encoding human AAT in primary human hepatocytes in culture, including hepatocytes from AAT deficient patients. Both expression and functional activity were investigated. Secreted AAT protein increased from 1,14 to 3,43 µg/ml in media from primary human hepatocytes following mRNA treatment as investigated by ELISA and western blot. The translated protein showed activity and protease inhibitory function as measured by elastase activity assay. Also, mRNA formulation in lipid nanoparticles was assessed for systemic delivery in both wild type mice and the NSG-PiZ transgenic mouse model of AAT deficiency. Systemic intravenous delivery of modified mRNA led to hepatic uptake and translation into a functioning protein in mice. These data support the use of systemic mRNA therapy as a potential treatment for AAT deficiency.
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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.