ArticleNature2014
Selection and evaluation of clinically relevant AAV variants in a xenograft liver model.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 284 papers, 2 of them syntheses 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
284 citing papers in PubMed, 2 syntheses or guidelines pooled it, 446 citations in OpenAlex.
- The promising novel therapies for familial hypercholesterolemia.Journal of clinical laboratory analysis · 2022Pooled it
- Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings.Frontiers in medicine · 2021Pooled it
- First-in-human nuclease-free homologous recombination-dependent gene editing in pediatric patients with methylmalonic acidemia: results of a phase 1/2 study.Gene therapy · 2026Trial
- Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A.The New England journal of medicine · 2021Trial
- Defining the safety and efficacy of liver-directed AAV gene therapy using a human liver tissue-equivalent platform.Molecular therapy. Advances · 2026Article
- Increased gene therapy efficacy through the use of extended half-life clotting factors.Blood advances · 2026Article
- Distinct YY dinucleotide periodicity in adeno-associated virus DNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Comparative Transduction Profiling of Four Intravenously Delivered AAV Capsids in the Neonatal Murine Nervous System.Biomedicines · 2026Article
- Orthogonal characterization of rAAV reveals vector attributes that drive ITR repair, self-complementary genome formation, and transgene expression.Molecular therapy. Nucleic acids · 2026Article
- Article
- Identification and Phylogenetic Characterisation of Novel Adeno-Associated Virus Capsids in Non-Human Primate Tissues.Cell proliferation · 2026Article
- Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026Review
- Role of viral protein ratio in the structure and separation of empty and full adeno-associated virus capsids: A molecular dynamics study.Molecular therapy. Advances · 2026Article
- Review
- Advancing Gene Therapy for Pancreatitis: From Genetic Insights to Clinical Translation.Research (Washington, D.C.) · 2026Review
- Disrupting Viral Persistence: CRISPR/Cas9-Based Strategies for Hepatitis B and C Treatment, and Challenges.Journal of cellular and molecular medicine · 2026Review
- Structure-guided engineering of prototype foamy virus Env identifies key residues for heparan sulfate binding and enhances transduction efficiency.Frontiers in bioengineering and biotechnology · 2026Article
- Article
- Species-specific AAVR dominates species-tropism of adeno-associated virus (AAV) vectors.Research square · 2025Article
- In vivo gene editing of human hematopoietic stem and progenitor cells using envelope-engineered virus-like particles.Nature biotechnology · 2025Article
224 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
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Recombinant adeno-associated viral (rAAV) vectors have shown early promise in clinical trials. The therapeutic transgene cassette can be packaged in different AAV capsid pseudotypes, each having a unique transduction profile. At present, rAAV capsid serotype selection for a specific clinical trial is based on effectiveness in animal models. However, preclinical animal studies are not always predictive of human outcome. Here, in an attempt to further our understanding of these discrepancies, we used a chimaeric human-murine liver model to compare directly the relative efficiency of rAAV transduction in human versus mouse hepatocytes in vivo. As predicted from preclinical and clinical studies, rAAV2 vectors functionally transduced mouse and human hepatocytes at equivalent but relatively low levels. However, rAAV8 vectors, which are very effective in many animal models, transduced human hepatocytes rather poorly-approximately 20 times less efficiently than mouse hepatocytes. In light of the limitations of the rAAV vectors currently used in clinical studies, we used the same murine chimaeric liver model to perform serial selection using a human-specific replication-competent viral library composed of DNA-shuffled AAV capsids. One chimaeric capsid composed of five different parental AAV capsids was found to transduce human primary hepatocytes at high efficiency in vitro and in vivo, and provided species-selected transduction in primary liver, cultured cells and a hepatocellular carcinoma xenograft model. This vector is an ideal clinical candidate and a reagent for gene modification of human xenotransplants in mouse models of human diseases. More importantly, our results suggest that humanized murine models may represent a more precise approach for both selecting and evaluating clinically relevant rAAV serotypes for gene therapeutic applications.
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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.