ArticleNature biotechnology2024
Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration.
Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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
93 citing papers in PubMed, 124 citations in OpenAlex.
- A phase 1/2 safety and efficacy study of TAK-754 gene therapy: The challenge of achieving durable factor VIII expression in haemophilia A clinical trials.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Trial
- Article
- Engineered muscle tissues with enhanced maturation enable the identification of clinically relevant rAAV products.Molecular therapy. Advances · 2026Article
- Long-read target enrichment sequencing for rAAV integration site analysis in engineered clones with targeted viral insertion.Molecular therapy. Nucleic acids · 2026Article
- Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.Molecular psychiatry · 2026Review
- Sequence-defined polymers for predictable gene delivery.Nature reviews. Chemistry · 2026Review
- Protein Nanocages as Versatile Vectors for Nucleic Acid Delivery: Main Systems and Their Loading Mechanisms.Molecular biotechnology · 2026Review
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- Adeno-Associated Virus Gene Therapy: Is There a Risk of Insertional Mutagenesis?Toxicologic pathology · 2026Review
- Safety, efficacy, and distal nerve Schwann cell biodistribution in mice and NHPs to support translation of AAV9 RNAi therapy for CMT1A.Molecular therapy. Nucleic acids · 2026Article
- Swine reporter model for preclinical evaluation and characterization of gene delivery vectors.Molecular therapy. Advances · 2026Article
- Advances in epigenetic regulation of potassium channels in chronic pain.Molecular biology reports · 2026Review
- Nickase NmCas9 unsilences paternal Ube3a in a mouse model of Angelman syndrome without causing AAV vector integration.Scientific reports · 2026Article
- Article
- The poly-(HA-GMA) hydrogel carrying AAV8-sTβRII alleviates scar formation in mice skin wound healing by inhibiting fibrosis.Gene therapy · 2026Article
- Metadata assessment of non-human primate studies of AAV9 uncovers potential tissue specific variation in expression efficiency.Gene therapy · 2026Article
- Testicular mRNA-LNP Delivery: A Novel Therapy for Genetic Spermatogenic Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RAAVioli: A comprehensive approach to characterizing AAV vector integrations and rearrangements.Molecular therapy. Advances · 2026Article
- Article
- Signal Peptide Engineering and Codon Optimization to Enhance α-Gal A Activity for rAAV Gene Therapy of Fabry Disease.Journal of inherited metabolic disease · 2026Article
33 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
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of liver-based adeno-associated virus (AAV) gene therapies is facing concerns about limited efficiency and durability of transgene expression. We evaluated nonhuman primates following intravenous dosing of AAV8 and AAVrh10 vectors for over 2 years to better define the mechanism(s) of transduction that affect performance. High transduction of non-immunogenic transgenes was achieved, although expression declined over the first 90 days to reach a lower but stable steady state. More than 10% of hepatocytes contained single nuclear domains of vector DNA that persisted despite the loss of transgene expression. Greater reductions in vector DNA and RNA were observed with immunogenic transgenes. Genomic integration of vector sequences, including complex concatemeric structures, were detected in 1 out of 100 cells at broadly distributed loci that were not in proximity to genes associated with hepatocellular carcinoma. Our studies suggest that AAV-mediated transgene expression in primate hepatocytes occurs in two phases: high but short-lived expression from episomal genomes, followed by much lower but stable expression, likely from integrated vectors.
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.