ArticleEMBO molecular medicine2023
AAV induces hepatic necroptosis and carcinoma in diabetic and obese mice dependent on Pebp1 pathway.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Long-term comparative analysis of AAV9-mediated gene replacement therapies for spinal muscular atrophy in mice.Nature communications · 2026Article
- PEBP1 inhibition as a therapeutic target for neurological recovery in ischemic stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation.Nature communications · 2025Article
- Unraveling the RKIP-YY1 axis: immune crosstalk in the pathogenesis of metabolic disorders.Frontiers in immunology · 2025Review
- The longitudinal kinetics of AAV5 vector integration profiles and evaluation of clonal expansion in mice.Molecular therapy. Methods & clinical development · 2024Article
- Adenovirus expressing nc886, an anti-interferon and anti-apoptotic non-coding RNA, is an improved gene delivery vector.Molecular therapy. Nucleic acids · 2024Article
- Multi-Omics Analysis Revealed the rSNPs Potentially Involved in T2DM Pathogenic Mechanism and Metformin Response.International journal of molecular sciences · 2024Article
- Programmed cell death in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cell death discovery · 2024Review
- Thorough molecular configuration analysis of noncanonical AAV genomes in AAV vector preparations.Molecular therapy. Methods & clinical development · 2024Article
- Gene Therapy for Genetic Syndromes: Understanding the Current State to Guide Future Care.Biotech (Basel (Switzerland)) · 2024Review
- AAV induces hepatic necroptosis and carcinoma in diabetic and obese mice dependent on Pebp1 pathway.EMBO molecular medicine · 2023Article
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14 authors.
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Abstract
Obesity and diabetes are risk factors for hepatocellular carcinoma (HCC); however, the underlying mechanisms are yet to be elucidated. Adeno-associated virus (AAV) frequently infects humans and has been widely used in gene therapy, but the risk of AAV infection such as HCC should be further evaluated. Here, we show that recombinant AAV injection caused liver injury, hepatic necroptosis, and HCC in db/db or high-fat diet-induced hyperglycemic and obese mice, but not in mice with only hyperglycemia or obesity. Prednisone administration or knockdown of Pebp1, highly expressed in db/db mice, alleviated hepatic injury and necroptosis induced by recombinant AAV in mice with diabetes and obesity. Inhibition of Pebp1 pathway also attenuated inflammation and necroptosis in vitro. Our findings show that AAV infection is a critical risk factor for HCC in patients with diabetes and obesity, and AAV gene therapy for these patients should be carefully evaluated. Both prednisone treatment and targeting Pebp1 pathway are promising strategies to alleviate inflammation and necroptosis that occurred in AAV gene therapy or related diseases.
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