ArticleEBioMedicine2018
Therapeutic Genome Editing With CRISPR/Cas9 in a Humanized Mouse Model Ameliorates α1-antitrypsin Deficiency Phenotype.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 81 citations in OpenAlex.
- Dual SORT LNPs for multi-organ base editing.Nature biotechnology · 2026Article
- Alpha-1 antitrypsin deficiency: genetics, clinical manifestations, AI prognostics, and advanced imaging in liver disease.Annals of medicine and surgery (2012) · 2025Review
- The power of mouse models in the diagnostic odyssey of patients with rare congenital anomalies.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Advanced delivery systems for gene editing: A comprehensive review from the GenE-HumDi COST Action Working Group.Molecular therapy. Nucleic acids · 2025Review
- Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.Cell reports. Medicine · 2025Article
- Expanding the CRISPR/Cas toolkit: applications in proteomics and theranostics.Frontiers in bioengineering and biotechnology · 2025Review
- CRISPR/Cas System: A Powerful Strategy to Improve Monogenic Human Diseases as Therapeutic Delivery; Current Applications and Challenges.Current gene therapy · 2025Review
- Gene Therapy for Inherited Liver Disease: To Add or to Edit.International journal of molecular sciences · 2024Review
- A review on molecular scissoring with CRISPR/Cas9 genome editing technology.Toxicology research · 2024Review
- Role of Serine Protease Inhibitors A1 and A3 in Ocular Pathologies.Investigative ophthalmology & visual science · 2024Review
- Breaking genetic shackles: The advance of base editing in genetic disorder treatment.Frontiers in pharmacology · 2024Review
- Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine.Frontiers in genome editing · 2024Review
- Delivery of gene editing therapeutics.Nanomedicine : nanotechnology, biology, and medicine · 2023Review
- What did CRISPR-Cas9 accomplish in its first 10 years?Biochemia medica · 2023Article
- CRISPR-Cas Technology as a Revolutionary Genome Editing tool: Mechanisms and Biomedical Applications.Iranian biomedical journal · 2023Review
- Advancing Treatment Strategies: A Comprehensive Review of Drug Delivery Innovations for Chronic Inflammatory Respiratory Diseases.Pharmaceutics · 2023Review
- Advances in CRISPR/Cas-Based Strategies on Zoonosis.Transboundary and emerging diseases · 2023Review
- Advances in CRISPR/Cas gene therapy for inborn errors of immunity.Frontiers in immunology · 2023Review
- CRISPR/Cas systems usher in a new era of disease treatment and diagnosis.Molecular biomedicine · 2022Review
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α1-antitrypsin (AAT) is a circulating serine protease inhibitor secreted from the liver and important in preventing proteolytic neutrophil elastase associated tissue damage, primarily in lungs. In humans, AAT is encoded by the SERPINA1 (hSERPINA1) gene in which a point mutation (commonly referred to as PiZ) causes aggregation of the miss-folded protein in hepatocytes resulting in subsequent liver damage. In an attempt to rescue the pathologic liver phenotype of a mouse model of human AAT deficiency (AATD), we used adenovirus to deliver Cas9 and a guide-RNA (gRNA) molecule targeting hSERPINA1. Our single dose therapeutic gene editing approach completely reverted the phenotype associated with the PiZ mutation, including circulating transaminase and human AAT (hAAT) protein levels, liver fibrosis and protein aggregation. Furthermore, liver histology was significantly improved regarding inflammation and overall morphology in hSERPINA1 gene edited PiZ mice. Genomic analysis confirmed significant disruption to the hSERPINA1 transgene resulting in a reduction of hAAT protein levels and quantitative mRNA analysis showed a reduction in fibrosis and hepatocyte proliferation as a result of editing. Our findings indicate that therapeutic gene editing in hepatocytes is possible in an AATD mouse model.
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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.