Reduction of liver tumor necrosis factor‐α expression by targeting delivery of antisense oligonucleotides into Kupffer cells protects rats from fulminant hepatitis

Dong, Lei; Zuo, Lijun; Xia, Suhua; Gao, Shuying; Zhang, Chenyu; Chen, Jiangning; Zhang, Junfeng

doi:10.1002/jgm.1293

Cited by 31 publications

(21 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the diverse inflammatory cytokines induced by LPS, TNF-a plays a central role in LPS/D-GalN-induced acute hepatitis [25][26][27]. LPS/D-GalN-induced hepatotoxicity could be completely blocked by neutralizing anti-TNF-a antibodies [13,28].…”

Section: Discussionmentioning

confidence: 99%

Protective effect of Gö6976, a PKD inhibitor, on LPS/d-GalN-induced acute liver injury in mice

Duan

Zhu

et al. 2010

Inflamm. Res.

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Protective effect of Gö6976, a PKD inhibitor, on LPS/d-GalN-induced acute liver injury in mice

Duan

Zhu

et al. 2010

Inflamm. Res.

View full text Add to dashboard Cite

show abstract

“…In parallel, treatment with adenovirus-mediated dominant negative form of the Fas-associated death domain (FADDdn), a downstream signaling molecule for Fas and TNFRs, inhibited the TNF /Galactosamine mediated hepatocellular apoptosis and significantly lowed the levels of serum transaminase in mice [114]. Furthermore, transfusion with Kupffer cells that had been in vitro transfected with TNF antisense oligonucleotide (ASO) mixed with galactosylated low molecular weight chitosan (ASO/GLC) significantly down-regulated the production of TNF and promoted the survival in rat model of fulminant hepatitis even after the onset of ALF [115]. Therefore, administering ASO/GLC complex may be a promising strategy for intervention of human ALF and worthwhile for clinical trial in ALF patients.…”

Section: Tumor Necrosis Factor (Tnf )/Tnfr Signalingmentioning

confidence: 97%

Gene Therapy for Acute Liver Failure

Zhu¹,

Li²,

Gao

2010

CGT

View full text Add to dashboard Cite

Acute liver failure (ALF) is a life-threatening medical emergency and occurs when the liver rapidly loses its function within a short period. ALF can develop secondary to a variety of causes. Currently, the orthotopic liver transplantation is the "Gold Standard" therapy for the disease. However, due to the limited availability of donor organs and rapid progression of the disease, the mortality of ALF remains high. Therefore, it is imperative to develop novel therapeutic reagents for ALF. Gene therapy by delivering a target gene to the patients appears to be a promising approach for the treatment of ALF. Here, we review the recent advance of gene therapy for ALF, focusing on the three technical elements, animal models, vehicles for gene delivery and technique for gene delivery, which are important for the success of gene therapy as well as the potential targets used for the treatment of ALF.

show abstract

“…In vivo characterization of a galactosylated chitosan for delivering AsODNs into Kupffer cells was reported by Dong et al (2009), who demonstrated inhibitor effect of AsODN= galactosylated chitosan system against the tumor necrosis factor-a expression. Dung et al (2007) suggested that sustained release of AsODN-loaded chitosan nanoparticles may be suitable for the local therapeutic application of periodontal diseases.…”

Section: Introductionmentioning

confidence: 93%

Topical Application of Antisense Oligonucleotide-Loaded Chitosan Nanoparticles to Rats

2010

View full text Add to dashboard Cite

Skin delivery of antisense oligonucleotides (AsODNs) has exciting potential in the treatment of skin diseases. However, the therapeutic applications of oligonucleotide-based therapies are limited by the instability of these molecules toward nucleases, short half-life in vivo, and insufficient cellular uptake. The purpose of this study was to investigate in vivo antisense effect of AsODN-loaded chitosan nanoparticles after topical application. AsODN-loaded chitosan nanoparticles were topically applied to Sprague Dawley rats (adult and baby). At 1, 3, 6, 9, and 12 days posttransfection, animals' skin samples were taken for measurement of beta-galactosidase (beta-Gal) expression and histological control. After topical application of AsODN-loaded chitosan nanoparticles in different doses, beta-Gal expression reduced significantly. Highest inhibition was observed after 6 days of transfection of nanoparticles. Free AsODNs exhibited 35% of beta-Gal inhibition on the first day. beta-Gal expression was inhibited in approximately 82-85% with transfection of nanoparticles containing 30 microg AsODNs at 6 days. The antisense effect of AsODN-loaded chitosan nanoparticle in baby skin was evaluated at 6 days: 77-86% of beta-Gal suppression was measured and differences between the doses were not significant. Thus, chitosan nanoparticles are useful carrier for delivery of AsODNs into skin cells of rats and may be used for topical application on human skin.

show abstract

Reduction of liver tumor necrosis factor‐α expression by targeting delivery of antisense oligonucleotides into Kupffer cells protects rats from fulminant hepatitis

Abstract: Background Fulminant liver failure can cause extreme mortality due to the lack of effective and targeting therapeutics for the disease. Novel therapeutics using antisense technology require an efficient and safe delivery system with Kupffer cell targeting ability.

Cited by 31 publications

References 47 publications

Protective effect of Gö6976, a PKD inhibitor, on LPS/d-GalN-induced acute liver injury in mice

Protective effect of Gö6976, a PKD inhibitor, on LPS/d-GalN-induced acute liver injury in mice

Gene Therapy for Acute Liver Failure

Topical Application of Antisense Oligonucleotide-Loaded Chitosan Nanoparticles to Rats

Contact Info

Product

Resources

About