Adeno-associated virus gene therapy prevents hepatocellular adenoma in murine model of glycogen storage disease type Ia

Wang, Lili

doi:10.1002/hep.25894

Cited by 2 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considering that both G6Pase‐a and G6PT are highly hydrophobic transmembrane proteins, enzyme‐replacement therapy is not suitable for patients with GSDI. Up to now, gene therapy studies using GSDIa and GSDIb models of mice or dogs have shown that AAV vectors encoding G6Pase‐α deliver transgene to the liver or kidney can be directed by the chicken β ‐actin promoter/CMV enhancer, 76,107,108 the mouse albumin promoter/enhancer, 79 the canine G6PC promoter, 82 or the human G6PC promoter 7,31,32,85,88,90 . Unfortunately, these animal models have severe hypoglycemia and a short life expectancy, which make them unsuitable for studying the long‐term complications of gene therapy on GSDI.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

“…Up to now, gene therapy studies using GSDIa and GSDIb models of mice or dogs have shown that AAV vectors encoding G6Pase-α deliver transgene to the liver or kidney can be directed by the chicken β -actin promoter/CMV enhancer, 76 , 107 , 108 the mouse albumin promoter/enhancer, 79 the canine G6PC promoter, 82 or the human G6PC promoter. 7 , 31 , 32 , 85 , 88 , 90 Unfortunately, these animal models have severe hypoglycemia and a short life expectancy, which make them unsuitable for studying the long-term complications of gene therapy on GSDI. These studies have well-demonstrated that the numbers of vector genomes could decline over time following rapid division of hepatocyte cell in young GSDIa mice; thus, the rAAV-mediated gene therapy cannot be durably and efficiently expressed in transgenic tissues.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

“…used AAV serotype 8‐based vectors expressing G6Pase to administrate to G6pc −/− mice or GSDIa dogs and that showed they could prolong median survival and restore hepatic G6Pase activity in affected models 39,82 . In subsequent years, a large body of research has systemically shown that the administration of rAAV pseudotype 2/8 or 2/7 vectors expressing the wild‐type human G6Pase‐α (rAAV‐G6PC) achieve high efficiency of transduction and correct metabolic abnormalities in the infused G6pc −/− mice or GSDIa dogs, directed by the human G6PC promoter/enhancer (GPE) 7,9,31,32,39,83–86 . More recently, Kim al.…”

Section: Clinical Management and Therapies Of Glycogen Storage Diseas...mentioning

confidence: 99%

“…39,82 In subsequent years, a large body of research has systemically shown that the administration of rAAV pseudotype 2/8 or 2/7 vectors expressing the wild-type human G6Pase-α (rAAV-G6PC) achieve high efficiency of transduction and correct metabolic abnormalities in the infused G6pc −/− mice or GSDIa dogs, directed by the human G6PC promoter/enhancer (GPE). 7,9,31,32,39,[83][84][85][86] More recently, Kim al. found that the G6pc −/− mice treated with rAAV-G6PC and rAAV-co(codon-optimized)-G6PC expressed more than 3% of normal hepatic G6Pase-α activity and prevented the development of agerelated obesity and insulin resistance.…”

Section: Bezafibratementioning

confidence: 99%

See 3 more Smart Citations

Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies

Zhong

Gou

Zhao

et al. 2023

Pediatric Discovery

View full text Add to dashboard Cite

Glycogen storage disease type I (GSDI) is an inherited metabolic disorder characterized by a deficiency of enzymes or proteins involved in glycogenolysis and gluconeogenesis, resulting in excessive intracellular glycogen accumulation. While GSDI is classified into four different subtypes based on molecular genetic variants, GSDIa accounts for approximately 80%. GSDIa and GSDIb are autosomal recessive disorders caused by deficiencies in glucose‐6‐phosphatase (G6Pase‐α) and glucose‐6‐phosphate‐transporter (G6PT), respectively. For the past 50 years, the care of patients with GSDI has been improved following elaborate dietary managements. GSDI patients currently receive dietary therapies that enable patients to improve hypoglycemia and alleviate early symptomatic signs of the disease. However, dietary therapies have many limitations with a risk of calcium, vitamin D, and iron deficiency and cannot prevent long‐term complications, such as progressive liver and renal failure. With the deepening understanding of the pathogenesis of GSDI and the development of gene therapy technology, there is great progress in the treatment of GSDI. Here, we review the underlying molecular genetics and the current clinical management strategies of GSDI patients with an emphasis on promising experimental gene therapies.

show abstract

Section: Discussion and Future Directionsmentioning

confidence: 99%

Section: Discussion and Future Directionsmentioning

confidence: 99%

Section: Clinical Management and Therapies Of Glycogen Storage Diseas...mentioning

confidence: 99%

Section: Bezafibratementioning

confidence: 99%

See 2 more Smart Citations

Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies

Zhong

Gou

Zhao

et al. 2023

Pediatric Discovery

View full text Add to dashboard Cite

show abstract

Ifit1 Protects Against Lipopolysaccharide and D-galactosamine–Induced Fatal Hepatitis by Inhibiting Activation of the JNK Pathway

et al. 2015

View full text Add to dashboard Cite

Treatment of mice with lipopolysaccharide (LPS) and the liver-specific transcriptional inhibitor D-(+)-galactosamine (GalN) induces fatal hepatitis, which is mediated by tumor necrosis factor α (TNF-α) and characterized by massive hepatic apoptosis. Previous studies suggest that GalN increases the sensitivity to LPS/TNF-α, probably by blocking the transcription of protective factors, but the identity of most of these factors is still unclear. Here, we report that Ifit1 protects against LPS/GalN-induced fatal hepatitis. Forced expression of Ifit1 in hepatocytes significantly diminished TNF-α-mediated apoptosis. Moreover, targeted expression of Ifit1 in the liver by recombinant adeno-associated virus serotype 8 protected mice from LPS/GalN-induced lethal hepatitis, which was associated with the inhibition of TNF-α-mediated activation of the c-Jun N-terminal kinase (JNK)-Bim cascade. Furthermore, Ifit1 bound to a scaffolding protein Axin and inhibited its function to mediate JNK activation. Together, our data demonstrate that Ifit1 is a novel protective factor that inhibits LPS/GalN-induced (TNF-α-mediated) fatal hepatitis, suggesting that Ifit1 is a potential therapeutic target for treatment of inflammatory liver diseases.

show abstract

Adeno-associated virus gene therapy prevents hepatocellular adenoma in murine model of glycogen storage disease type Ia

Cited by 2 publications

References 21 publications

Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies

Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies

Ifit1 Protects Against Lipopolysaccharide and D-galactosamine–Induced Fatal Hepatitis by Inhibiting Activation of the JNK Pathway

Contact Info

Product

Resources

About