Growth factors improve gene expression after lentiviral transduction in human adult and fetal hepatocytes

Selden, Clare; Mellor, Neil; Rees, Myrddin; Laurson, Joanna; Kirwan, Michael; Escors, David; Collins, Mary; Hodgson, H. J. F.

doi:10.1002/jgm.1000

Cited by 27 publications

(39 citation statements)

References 28 publications

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“…However, higher H-IL6 concentrations (40 and 50 ng ml -1 ) were toxic, which led cells to die. Selden et al (2007) have also used a third-generation lentiviral vector at MOI 1 and reported that about 15% of human hepatocytes could 1). Then, the cells were treated with or without H-IL-6.…”

Section: Discussionmentioning

confidence: 98%

The chimeric cytokine Hyper-IL-6 enhances the efficiency of lentiviral gene transfer in hepatocytes both in vitro and in vivo

Picanço‐Castro¹,

Fontes²,

Heinz³

et al. 2007

Biotechnol Lett

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Lentiviral vectors have been used for gene transfer into the liver but their ability to efficiently transduce quiescent hepatocytes remains controversial. Lentivirus-mediated gene transfer is more efficient in cycling cells. We determine the effect of H-IL6 in the lentiviral transduction. The lentiviral vector was used to transduce HepG2 cells and mice liver cells, previously treated with H-IL6. The highest transduction level was observed in HepG2 cells treated with 30 ng/mL H-IL6 and in the mice that received 4 microg H-IL6. Our results suggest that H-IL6 is an inducer of lentiviral gene transfer into the liver cells without any toxicity.

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Section: Discussionmentioning

confidence: 98%

The chimeric cytokine Hyper-IL-6 enhances the efficiency of lentiviral gene transfer in hepatocytes both in vitro and in vivo

Picanço‐Castro¹,

Fontes²,

Heinz³

et al. 2007

Biotechnol Lett

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“…PHH were isolated by collagenase perfusion (23). Isolated hepatocytes were plated into 24-well type I collagen-coated plates (BD Biosciences) using hepatocyte basal media with supplements (Lonza).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Na+-Taurocholate Co-transporting Polypeptide-mediated Bile Acid Transport by Cholestatic Sulfated Progesterone Metabolites

Abu‐Hayyeh

Martinez-Becerra

Kadir

et al. 2010

Journal of Biological Chemistry

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Sulfated progesterone metabolite (P4-S) levels are raised in normal pregnancy and elevated further in intrahepatic cholestasis of pregnancy (ICP), a bile acid-liver disorder of pregnancy. ICP can be complicated by preterm labor and intrauterine death. The impact of P4-S on bile acid uptake was studied using two experimental models of hepatic uptake of bile acids, namely cultured primary human hepatocytes (PHH) and Na ؉ -taurocholate co-transporting polypeptide (NTCP)-expressing Xenopus laevis oocytes. Two P4-S compounds, allopregnanolone-sulfate (PM4-S) and epiallopregnanolone-sulfate (PM5-S), reduced [ 3 H]taurocholate (TC) uptake in a dose-dependent manner in PHH, with both Na ؉ -dependent and -independent bile acid uptake systems significantly inhibited. PM5-S-mediated inhibition of TC uptake could be reversed by increasing the TC concentration against a fixed PM5-S dose indicating competitive inhibition. Experiments using NTCP-expressing Xenopus oocytes confirmed that PM4-S/PM5-S are capable of competitively inhibiting NTCPmediated uptake of [ 3 H]TC. Total serum PM4-S ؉ PM5-S levels were measured in non-pregnant and third trimester pregnant women using liquid chromatography-electrospray tandem mass spectrometry and were increased in pregnant women, at levels capable of inhibiting TC uptake. In conclusion, pregnancy levels of P4-S can inhibit Na ؉ -dependent and -independent influx of taurocholate in PHH and cause competitive inhibition of NTCP-mediated uptake of taurocholate in Xenopus oocytes.Normal pregnancy is characterized by altered bile acid homeostasis, and two recent studies have reported asymptomatic hypercholanemia of pregnancy in 10 -40% of pregnant women (1, 2). Approximately 25% of women with asymptomatic hypercholanemia of pregnancy subsequently develop intrahepatic cholestasis of pregnancy (ICP), 4 a liver disorder that presents with pruritus, raised serum bile acids, and liver transaminases (3). In pregnancies complicated by maternal serum bile acid levels of Ͼ40 M, there are increased rates of spontaneous preterm labor, fetal asphyxial events, and meconium-stained amniotic fluid (3). ICP may also be complicated by third trimester intrauterine death (3, 4).ICP has a complex etiology with genetic and endocrine components. Parous sisters have a 12-fold increased risk (5), and in ϳ10% of ICP cases, mutations have been identified in genes that encode biliary transporters (6 -9) and the primary bile acid sensor farnesoid X receptor (NR1H4) (10). Furthermore, the V444A polymorphism in the ABCB11 gene is a population risk factor for ICP (8), and ICP patients homozygous for the polymorphism have been shown to have increased bile acid levels when compared with controls (11).Cholestatic metabolites of estrogen and progesterone influence bile acid metabolism and transport. A subgroup of women with a history of ICP who take the oral contraceptive pill or exogenous estrogens develop pruritus and hepatic impairment (4). In addition, administration of oral micronized natural progesterone for prophylaxis of...

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“…For example, incorporation of WPRE into a lentiviral system has been shown to increase lentiviral titer and transgene expression by improving the half-life, export and polyadenylation of mRNA [82]. WPRE-incorporated LV was able to efficiently transduce smooth muscle cells, hepatocytes, neural cells and blood cells [84][85][86][87], demonstrating that extensive modification of lentiviral vectors can induce safe, efficient and long-term transgene expression in perennial diseases.…”

Section: Retrovirusesmentioning

confidence: 99%

Evolving Lessons on Nanomaterial-Coated Viral Vectors for Local and Systemic Gene Therapy

Kasala

Yoon

Hong

et al. 2016

Nanomedicine (Lond.)

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Viral vectors are promising gene carriers for cancer therapy. However, virus-mediated gene therapies have demonstrated insufficient therapeutic efficacy in clinical trials due to rapid dissemination to nontarget tissues and to the immunogenicity of viral vectors, resulting in poor retention at the disease locus and induction of adverse inflammatory responses in patients. Further, the limited tropism of viral vectors prevents efficient gene delivery to target tissues. In this regard, modification of the viral surface with nanomaterials is a promising strategy to augment vector accumulation at the target tissue, circumvent the host immune response, and avoid nonspecific interactions with the reticuloendothelial system or serum complement. In the present review, we discuss various chemical modification strategies to enhance the therapeutic efficacy of viral vectors delivered either locally or systemically. We conclude by highlighting the salient features of various nanomaterial-coated viral vectors and their prospects and directions for future research.

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Growth factors improve gene expression after lentiviral transduction in human adult and fetal hepatocytes

Abstract: This has implications for the design of regimes for liver cell gene therapy, allowing marked reduction of MOIs, and reducing both cost and risk of viral-mediated toxicity.

Cited by 27 publications

References 28 publications

The chimeric cytokine Hyper-IL-6 enhances the efficiency of lentiviral gene transfer in hepatocytes both in vitro and in vivo

The chimeric cytokine Hyper-IL-6 enhances the efficiency of lentiviral gene transfer in hepatocytes both in vitro and in vivo

Inhibition of Na+-Taurocholate Co-transporting Polypeptide-mediated Bile Acid Transport by Cholestatic Sulfated Progesterone Metabolites

Evolving Lessons on Nanomaterial-Coated Viral Vectors for Local and Systemic Gene Therapy

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