Construction of a regulable gene therapy vector targeting for hepatocellular carcinoma

Lu, Shao-Ying; Sui, Yan-Fang; Li, Zengshan; Pan, Cheng; Ye, Jing; Wang, Wenyong

doi:10.3748/wjg.v9.i4.688

Cited by 15 publications

(6 citation statements)

References 27 publications

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“…AFP promoter constructs have been applied in a variety of studies and have been demonstrated to effectively target reporter or therapeutic genes to HCC cells, while avoiding toxicity to normal liver cells. [22][23][24][25] Expression of AFP is regulated by four distinct regulatory elements, including the proximal promoter and three enhancer domains (enhancers I, II, III). In our study, to target NIS gene transfer to hepatoma cells we applied a 2666 bp mouse AFP promoter construct consisting of the basal promoter and enhancer I element, that are known to provide maximal tissue specificity and promoter activity.…”

Section: 16mentioning

confidence: 99%

α-Fetoprotein promoter-targeted sodium iodide symporter gene therapy of hepatocellular carcinoma

et al. 2007

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Due to limited treatment options the prognosis of patients with advanced hepatocellular cancer (HCC) has remained poor. To investigate an alternative therapeutic approach, we examined the feasibility of radioiodine therapy of HCC following human sodium iodide symporter (NIS) gene transfer using a mouse a-fetoprotein (AFP) promoter construct to target NIS expression to HCC cells. For this purpose, the murine Hepa 1-6 and the human HepG2 hepatoma cell lines were stably transfected with NIS cDNA under the control of the tumor-specific AFP promoter. The stably transfected Hepa 1-6 cell line showed a 10-fold increase in iodide accumulation, while HepG2 cells accumulated 125 I approximately 60-fold. Tumor-specific NIS expression was confirmed on mRNA level by northern blot analysis, and on protein level by immunostaining, that revealed primarily membrane-associated NIS-specific immunoreactivity.In an in vitro clonogenic assay up to 78% of NIS-transfected Hepa 1-6 and 93% of HepG2 cells were killed by

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Section: 16mentioning

confidence: 99%

α-Fetoprotein promoter-targeted sodium iodide symporter gene therapy of hepatocellular carcinoma

et al. 2007

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“…In an attempt to develop a system that can also be applied to liver cancer, we searched for a liver cancerspecific promoter and identified several potential liver cancer-specific promoter candidates, including a-fetoprotein (AFP) basic promoter and AFP basic promoter combined with AFP enhancers (eAFP), both of which have already been known for being highly liver cancer specific (Kim and Wang, 2003;Lu et al, 2003;Shi et al, 2004;Suriawinata and Xu, 2004;Lemken et al, 2005;Guan et al, 2006). AFP, produced by the yolk sac and liver, is expressed at high levels during early development in fetus and decreases to a low or undetected level in adults (Abelev and Eraiser, 1999).…”

Section: Introductionmentioning

confidence: 99%

Targeted hepatocellular carcinoma proapoptotic BikDD gene therapy

Dai

Yeh

et al. 2010

Oncogene

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“…The size of NPs is important for a favourable cellular uptake. Polycation/DNA gene‐delivery systems mostly enter the cell by endocytosis or pinocytosis, meaning that they have a size requirement of less than 100 nm for maximum endocytosis by non‐specialized cells [16]. Smaller NPs show a higher accumulation in tissues and a prolonged in vivo half‐life due to their avoidable capture by the reticuloendothelial system.…”

Section: Resultsmentioning

confidence: 99%

A novel PEGylation of chitosan nanoparticles for gene delivery

Zhang

Chen

Yang-de

et al. 2007

Biotech and App Biochem

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CS (chitosan) has emerged as a promising non-viral vector for gene delivery because of its ability to form complexes with pDNA (plasmid DNA) and enhance its transport across cellular membranes through endocytosis. Complexes of CS and pDNA may improve transfection efficiency; however, they are not capable of sustained DNA release and prolonging gene transfer. In order to achieve prolonged delivery of CS-DNA complexes, we prepared CS NP (nanoparticle) and CS-DNA complexes. alpha-Methoxy-omega-succinimidylpoly(ethylene glycol) was then conjugated to the surface of CS-DNA complexes using an active ester scheme; finally, the potential of PEGylation [poly(ethylene glycol)ylation] of CS NP as a non-viral gene-delivery vector to transfer exogenous genes in vitro and in vivo were examined. Electrophoretic analysis suggested that CS NPs could protect the DNA from nuclease degradation. The pDNA carried by CS NPs could enter and be expressed in HepG2 cells. However, the transfection efficiency was very low and the highest dose of DNA transferred was 1.6 microg. The transfection activities of CS-DNA-PEG were preserved and a higher dose (2.4 microg) of pDNA was transferred. This indicated that the transfection efficiency of the PEGylated complexes had been improved. In vivo experiments also showed that CS-DNA-PEG complexes mediated higher gene expression in tissues than did CS-DNA complexes, and that gene expression in tumours induced by CS-DNA-PEG complexes was the highest of all. These results suggested that PEGylation of CS-DNA complexes improves non-viral gene delivery in vitro or in vivo and has the potential to deliver therapeutic genes directly into hepatoma tissues.

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Construction of a regulable gene therapy vector targeting for hepatocellular carcinoma

Abstract: This recombinant expression vector can be used as a gene therapy vector for HCC. The expression of tumor killing gene will be confined within the site of tumor and the activity of which can be regulated by retinoic acid.

Cited by 15 publications

References 27 publications

α-Fetoprotein promoter-targeted sodium iodide symporter gene therapy of hepatocellular carcinoma

α-Fetoprotein promoter-targeted sodium iodide symporter gene therapy of hepatocellular carcinoma

Targeted hepatocellular carcinoma proapoptotic BikDD gene therapy

A novel PEGylation of chitosan nanoparticles for gene delivery

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