ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Liver Injury Increases the Incidence of HCC following AAV Gene Therapy in Mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65 citing papers in PubMed, 100 citations in OpenAlex.
- Magnetoreceptor Promotes Hepatocellular Carcinoma Development and Blunts Sorafenib-Induced Ferroptosis by Regulating Iron Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Long-read target enrichment sequencing for rAAV integration site analysis in engineered clones with targeted viral insertion.Molecular therapy. Nucleic acids · 2026Article
- Transplantation as disease modifying therapy in the era of gene therapy medicinal products - health policy considerations.Orphanet journal of rare diseases · 2026Review
- Structural basis of liver de-targeting and neuronal tropism of CNS-targeted AAV capsids.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Adeno-Associated Virus Gene Therapy: Is There a Risk of Insertional Mutagenesis?Toxicologic pathology · 2026Review
- Optimized AAV vector enables potent therapeutic rescue of inherited glycosylphosphatidylinositol deficiency in mice.Molecular therapy. Advances · 2026Article
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- Biomaterial-assisted neuralization strategies for tissue engineering applications.Materials today. Bio · 2026Review
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- Malignancy and gene therapy in hemophilia.Research and practice in thrombosis and haemostasis · 2026Article
- 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
- AAV-dCas9 vector unsilences paternal Ube3a in neurons by impeding Ube3a-ATS transcription.Communications biology · 2025Article
- Gene therapy as an innovative approach to the treatment of hemophilia B-a review.Journal of applied genetics · 2025Review
- Gene-based therapies for steatotic liver disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Article
- Rescue of the endogenous FVIII expression in hemophilia A mice using CRISPR-Cas9 mRNA LNPs.Molecular therapy. Nucleic acids · 2024Article
- Review
- Optimizing liver health before and after gene therapy for hemophilia A.Blood advances · 2024Review
- The longitudinal kinetics of AAV5 vector integration profiles and evaluation of clonal expansion in mice.Molecular therapy. Methods & clinical development · 2024Article
- Lipid nanoparticle technology-mediated therapeutic gene manipulation in the eyes.Molecular therapy. Nucleic acids · 2024Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Adeno-associated virus (AAV) integrates into host genomes at low frequency, but when integration occurs in oncogenic hotspots it can cause hepatocellular carcinoma (HCC). Given the possibility of recombinant AAV (rAAV) integration leading to HCC, common causes of liver inflammation like non-alcoholic fatty liver disease (NAFLD) may increase the risk of rAAV-induced HCC. A rAAV targeting the oncogenic mouse Rian locus was used, and as expected led to HCC in all mice infected as neonates, likely due to growth-related hepatocyte proliferation in young mice. Mice infected with rAAV as adults did not develop HCC unless they were fed a diet leading to NAFLD, with increased inflammation and hepatocyte proliferation. Female mice were less susceptible to rAAV-induced HCC, and male mice with NAFLD treated with estrogen exhibited less inflammation and immune exhaustion associated with oncogenesis compared to those without estrogen. Adult NAFLD mice infected with a non-targeted control rAAV also developed HCC, though only half as frequently as those exposed to the Rian targeted rAAV. This study shows that adult mice exposed to rAAV gene therapy in the context of chronic liver disease developed HCC at high frequency, and thus warrants further study in humans given the high prevalence of NAFLD in the population.
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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.