ArticleGene therapy2018
Targeted in vivo knock-in of human alpha-1-antitrypsin cDNA using adenoviral delivery of CRISPR/Cas9.
Article in Gene therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- CRISPR-Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus.Molecular biology reports · 2026Review
- Adenoviral Vectors in Gene Therapy: A Detailed Overview.Iranian biomedical journal · 2026Review
- Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects.Expert reviews in molecular medicine · 2025Review
- Overcoming the Delivery Challenges in CRISPR/Cas9 Gene Editing for Effective Cancer Treatment: A Review of Delivery Systems.International journal of medical sciences · 2025Review
- Lipid Nanoparticles Enable Efficient In Vivo DNA Knock-In via HITI-Mediated Genome Editing.Biomolecules · 2024Article
- CRISPR-Cas Genome Editing inHuman gene therapy · 2024Article
- Review
- Approaches to Therapeutic Gene Editing in Alpha-1 Antitrypsin Deficiency.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Review
- Monitoring the Secretion and Activity of Alpha-1 Antitrypsin in Various Mammalian Cell Types.Methods in molecular biology (Clifton, N.J.) · 2024Article
- CRISPR-Cas9 Direct Fusions for Improved Genome Editing via Enhanced Homologous Recombination.International journal of molecular sciences · 2023Review
- Adenoviral vectors infect B lymphocytes in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Applications and Research Advances in the Delivery of CRISPR/Cas9 Systems for the Treatment of Inherited Diseases.International journal of molecular sciences · 2023Review
- Viral vectors and extracellular vesicles: innate delivery systems utilized in CRISPR/Cas-mediated cancer therapy.Cancer gene therapy · 2023Review
- Modern Approaches to Mouse Genome Editing Using the CRISPR-Cas Toolbox and Their Applications in Functional Genomics and Translational Research.Advances in experimental medicine and biology · 2023Review
- Immunogenicity of CRISPR therapeutics-Critical considerations for clinical translation.Frontiers in bioengineering and biotechnology · 2023Review
- Review
- Viral Vectors for theFrontiers in bioengineering and biotechnology · 2022Review
- HMEJ-mediated site-specific integration of a myostatin inhibitor increases skeletal muscle mass in porcine.Molecular therapy. Nucleic acids · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Serum deficiency diseases such as alpha-1-antitrypsin deficiency are characterized by reduced function of serum proteins, caused by deleterious genetic mutations. These diseases are promising targets for genetic interventions. Gene therapies using viral vectors have been used to introduce correct copies of the disease-causing gene in preclinical and clinical studies. However, these studies highlighted that disease-alleviating gene expression is lost over time. Integration into a specific chromosomal site could provide lasting therapeutic expression to overcome this major limitation. Additionally, targeted integration could avoid detrimental mutagenesis associated with integrative vectors, such as tumorigenesis or functional gene perturbation. To test if adenoviral vectors can facilitate long-term gene expression through targeted integration, we somatically incorporated the human alpha-1-antitrypsin gene into the ROSA26 "safe harbor" locus in murine livers, using CRISPR/Cas9. We found adenoviral-mediated delivery of CRISPR/Cas9 achieved gene editing outcomes persisting over 200 days. Furthermore, gene knock-in maintained greater levels of the serum protein than provided by episomal expression. Importantly, our "knock-in" approach is generalizable to other serum proteins and supports in vivo cDNA replacement therapy to achieve stable gene expression.
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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.