ArticleNature biotechnology2016
A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice.
Article in Nature biotechnology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 317 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
317 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review of Genetic Substrate Reduction Therapy in Lysosomal Storage Diseases: Opportunities, Challenges and Delivery Systems.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Pooled it
- Systematic Profiling of ssODN Determinants Establishes Optimized LbCas12a-Mediated HDR for Precise Genome Editing inJournal of fungi (Basel, Switzerland) · 2026Article
- Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Adaptive model-guided protein evolution with sparse data optimizes compact eukaryotic genome editors.Nature biotechnology · 2026Article
- Restoring the Balance: CRISPRa-Driven β-Tubulin Compensation as a Strategy for Tubulinopathy Treatment.International journal of molecular sciences · 2026Article
- Application of CRISPR-Cas9-Based Gene Editing Technology in Inherited Liver Diseases.International journal of molecular sciences · 2026Review
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Disrupting Viral Persistence: CRISPR/Cas9-Based Strategies for Hepatitis B and C Treatment, and Challenges.Journal of cellular and molecular medicine · 2026Review
- Review
- AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.Nature biotechnology · 2025Article
- A modular strategy for extracellular vesicle-mediated CRISPR-Cas9 delivery through aptamer-based loading and UV-activated cargo release.Nature communications · 2025Article
- A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress.Genome research · 2025Article
- CRISPR Technology in Disease Management: An Updated Review of Clinical Translation and Therapeutic Potential.Cell proliferation · 2025Article
- Current Treatment Modalities for Urea Cycle Disorders.Paediatric drugs · 2025Review
- High-density brush-shaped polymer lipids reduce anti-PEG antibody binding for repeated administration of mRNA therapeutics.Nature materials · 2025Article
- Rescue of neurologic disease in mucopolysaccharidosis type II mice via AAV-mediated liver delivery of brain-penetrating iduronate-2-sulfatase.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Engineering adeno-associated viral vectors for CRISPR/Cas based in vivo therapeutic genome editing.Biomaterials · 2025Review
- Article
- Optimized dual-AAV base editor delivery system with enhanced editing efficiency and virion production titer.Synthetic and systems biotechnology · 2025Article
257 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Many genetic liver diseases in newborns cause repeated, often lethal, metabolic crises. Gene therapy using nonintegrating viruses such as adeno-associated virus (AAV) is not optimal in this setting because the nonintegrating genome is lost as developing hepatocytes proliferate. We reasoned that newborn liver may be an ideal setting for AAV-mediated gene correction using CRISPR-Cas9. Here we intravenously infuse two AAVs, one expressing Cas9 and the other expressing a guide RNA and the donor DNA, into newborn mice with a partial deficiency in the urea cycle disorder enzyme, ornithine transcarbamylase (OTC). This resulted in reversion of the mutation in 10% (6.7-20.1%) of hepatocytes and increased survival in mice challenged with a high-protein diet, which exacerbates disease. Gene correction in adult OTC-deficient mice was lower and accompanied by larger deletions that ablated residual expression from the endogenous OTC gene, leading to diminished protein tolerance and lethal hyperammonemia on a chow diet.
Indexed as
Identifiers
What OpenQuestion holds
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.