ArticleNature biotechnology2025
AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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
22 citing papers in PubMed.
- Probing the Capsid: pH-Driven Gating at the AAV 5-Fold Pore and Its Role in Peptide Ligand Binding.Pharmaceutics · 2026Article
- Safety of Adeno-Associated Viral Vectors in Gene Therapy: Mechanisms of Toxicity, Clinical Risks, and Strategies for Their Minimization.International journal of molecular sciences · 2026Review
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Implications of the FDA's new plausible mechanism framework for the development of a personalized in vivo prime editing platform.American journal of human genetics · 2026Review
- Spatial transcriptomics and single-nucleus RNA sequencing reveal rAAV2- and rAAV9-specific transduction signatures in the mouse liver.Gene therapy · 2026Article
- Gene Therapy in Hemophilia: Clinical Advances, Immunological Challenges, and Emerging Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Deaths in gene therapy of Duchenne muscular dystrophy and other diseases: Underlying mechanisms and mitigating strategies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Normothermic perfusion of human livers for profiling lentiviral vector pharmacokinetics and transduction.Molecular therapy. Advances · 2026Article
- Beyond CRISPR: next-gen precision engineering of CAR-NK cells for enhanced persistence, trafficking, and tumor eradication.Cancer cell international · 2026Review
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- Revealing the potential of non-transplanted donor organs: a comparative analysis in the Eurotransplant region.Transplant international : official journal of the European Society for Organ Transplantation · 2026Article
- Emerging Approaches for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease: The Application of Nanomedicines.International journal of nanomedicine · 2026Review
- OTULIN: a master regulator of linear ubiquitin homeostasis in immune signaling, inflammation, and disease.Frontiers in immunology · 2026Review
- Viral vector-based gene therapies in the clinic: An update.Bioengineering & translational medicine · 2026Review
- Species-specific AAVR dominates species-tropism of adeno-associated virus (AAV) vectors.Research square · 2025Article
- Human liver immunology: from in vitro models to new insights.Cellular & molecular immunology · 2025Review
- Screening of Single-Domain Antibodies to Adeno-Associated Viruses with Cross-Serotype Specificity and a Wide pH Tolerance.Viruses · 2025Article
- Identification of a robust promoter in mouse and human hepatocytes by in vivo biopanning of a barcoded AAV library.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene-based therapies for steatotic liver disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The deLIVERed promises of gene therapy: Past, present, and future of liver-directed gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Funding
Abstract
Therapeutic efficacy and safety of adeno-associated virus (AAV) liver gene therapy depend on capsid choice. To predict AAV capsid performance under near-clinical conditions, we established side-by-side comparison at single-cell resolution in human livers maintained by normothermic machine perfusion. AAV-LK03 transduced hepatocytes much more efficiently and specifically than AAV5, AAV8 and AAV6, which are most commonly used clinically, and AAV-NP59, which is better at transducing human hepatocytes engrafted in immune-deficient mice. AAV-LK03 preferentially transduced periportal hepatocytes in normal liver, whereas AAV5 targeted pericentral hepatocytes in steatotic liver. AAV5 and AAV8 transduced liver sinusoidal endothelial cells as efficiently as hepatocytes. AAV capsid and steatosis influenced vector episome formation, which determines gene therapy durability, with AAV5 delaying concatemerization. Our findings inform capsid choice in clinical AAV liver gene therapy, including consideration of disease-relevant hepatocyte zonation and effects of steatosis, and facilitate the development of AAV capsids that transduce hepatocytes or other therapeutically relevant cell types in the human liver with maximum efficiency and specificity.
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.