Efficient and Targeted Transduction of Nonhuman Primate Liver With Systemically Delivered Optimized AAV3B Vectors

Li, Shaoyong; Chen, Ling; Zhong, Li; Li, Mengxin; Su, Qin; He, Ran; Tang, Qiushi; Greiner, Dale L.; Shultz, Leonard D.; Brehm, Michael A.; Flotte, Terence R.; Mueller, Christian; Srivastava, Arun; Gao, Guangping

doi:10.1038/mt.2015.174

Cited by 75 publications

(84 citation statements)

References 46 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rag2 null IL2rg null mice that express active caspase 8 fused with FK506 binding domain can be treated with FK506 to selectively kill mouse hepatocytes. A recent report suggests that NSG mice transgenically expressing a mutant allele of SERPINA1* (NSG-PiZ) crippled murine hepatocytes enabling human hepatocyte engraftment and in vivo targeting of the human hepatocytes by rAAV8 (75). …”

Section: Human-murine Liver Chimeric Mouse Models For Infectious Diseasementioning

confidence: 99%

Humanized Mouse Models of Clinical Disease

Walsh

Kenney

Jangalwe

et al. 2017

Annu. Rev. Pathol. Mech. Dis.

433

384

View full text Add to dashboard Cite

Immunodeficient mice engrafted with functional human cells and tissues, i.e., “humanized mice”, have become increasingly important as small pre-clinical animal models for the study of human diseases. Since the description of immunodeficient mice bearing mutations in the IL2 receptor common gamma chain (IL2rgnull) in the early 2000’s, investigators have been able to engraft murine recipients with human hematopoietic stem cells that develop into functional human immune systems. These mice can also be engrafted with human tissues such as islets, liver, skin, and most solid and hematologic cancers. Humanized mice are permitting significant progress in studies of human infectious disease, cancer, regenerative medicine, graft versus host disease, allergies, and immunity. Ultimately, use of humanized mice may lead to the implementation of truly “personalized” medicine in the clinic. This review discusses recent progress in the development and use of humanized mice, and highlights their utility for the study of human diseases.

show abstract

Section: Human-murine Liver Chimeric Mouse Models For Infectious Diseasementioning

confidence: 99%

Humanized Mouse Models of Clinical Disease

Walsh

Kenney

Jangalwe

et al. 2017

Annu. Rev. Pathol. Mech. Dis.

433

384

View full text Add to dashboard Cite

show abstract

“…The nature and abundance of these extracellular glycans vary dramatically between different species and at different developmental stages. Since AAV attachment is a determining factor in systemic delivery, cautions should be taken to extrapolate re-engineered capsids for different applications [102,115,116,137]. …”

Section: Re-engineering Aav For Improved Systemic Deliverymentioning

confidence: 99%

Systemic delivery of adeno-associated viral vectors

Duan

2016

Current Opinion in Virology

View full text Add to dashboard Cite

For diseases like muscular dystrophy, an effective gene therapy requires bodywide correction. Systemic viral vector delivery has been attempted since early 90s. Yet a true success was not achieved until mid-2000 when adeno-associated virus (AAV) serotype-6, 8 and 9 were found to result in global muscle transduction in rodents following intravenous injection. The simplicity of the technique immediately attracts attention. Marvelous whole body amelioration has been achieved in rodent models of many diseases. Scale-up in large mammals also shows promising results. Importantly, the first systemic AAV-9 therapy was initiated in patients in April 2014. Recent studies have now begun to reveal molecular underpinnings of systemic AAV delivery and to engineer new AAV capsids with superior properties for systemic gene therapy.

show abstract

“…Huh7 cells were purchased from Zhongqiaoxinzhou Biotech Inc. (Shanghai, China) and treated as described previously [14, 15]. Cells were grown in high-glucose DMEM medium with 10% fetal bovine serum, 100 IU/ml penicillin, and 50 µg/ml streptomycin sulphate.…”

Section: Methodsmentioning

confidence: 99%

CCL2 is Upregulated by Decreased miR-122 Expression in Iron-Overload-Induced Hepatic Inflammation

Tang¹,

Jia²,

Niu³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Iron overload (IO) is accompanied by hepatic inflammation. The chemokine (C-C motif) ligand 2 (CCL2) mediates inflammation, and its overexpression is associated with IO. However, whether IO results in CCL2 overexpression in the liver and the underlying mechanisms are unclear. Methods: We subjected mice to IO by administering intraperitoneal injections of dextran-iron or by feeding mice a 3% dextran-iron diet to observe the effects of IO on miR-122/CCL2 expression through real-time qPCR and Western blot analysis. We also used indicators, including the expression of the inflammatory cytokine, the inflammation score based on H&E staining and the serum content of ALT and AST to evaluate the effects of IO on hepatic inflammation. Meanwhile, we observed the effects of vitamin E on IO-induced hepatic inflammation. In cells, we used 100 µΜ FeSO₄ or 30 µΜ Holo-Tf to produce IO and observed the roles of miR-122 in regulating CCL2 expression by using miR-122 mimics or inhibitors to overexpress or inhibit miR-122. Then, we used a dual-luciferase reporter assay to prove that miR-122 regulates CCL2 expression through direct binding to its complementary sequence in the CCL2 mRNA 3’UTR. Results: IO induces the downregulation of miR-122 and the upregulation of CCL2, as well as inflammatory responses both in vitro and in vivo. Although IO-induced oxidative stress is eliminated by the antioxidant vitamin E, IO-induced hepatic inflammation still exists, which probably can be explained by the fact that vitamin E has no effects on the miR-122/CCL2 pathway. In in vitro experiments, the overexpression and inhibition of miR-122 significantly reduced and increased CCL2 expression, respectively. The dual-luciferase reporter assay indicates that miR-122 binds CCL2 mRNA 3’UTR. Conclusion: We propose the roles of miR-122/CCL2 in IO-induced hepatic inflammation. Our studies should provide a new clue for developing clinical strategies for patients with IO.

show abstract

Efficient and Targeted Transduction of Nonhuman Primate Liver With Systemically Delivered Optimized AAV3B Vectors

Cited by 75 publications

References 46 publications

Humanized Mouse Models of Clinical Disease

Humanized Mouse Models of Clinical Disease

Systemic delivery of adeno-associated viral vectors

CCL2 is Upregulated by Decreased miR-122 Expression in Iron-Overload-Induced Hepatic Inflammation

Contact Info

Product

Resources

About