Increased Expression of DNA Cointroduced with Nuclear Protein in Adult Rat Liver

Kaneda, Yasufumi; Iwai, Kunimitsu; Uchida, Tsuyoshi

doi:10.1126/science.2911748

Cited by 449 publications

(76 citation statements)

References 27 publications

(20 reference statements)

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“…For this purpose a retroviral or adenoviral transfer method, or a liposome-mediated transfer method may be suitable [23,24,30]. We are currently in the process of examining these methods using diabetic animals.…”

Section: A No Stimulantsmentioning

confidence: 99%

“…The mice exhibited normoglycemia a week after the implantation of proinsulin-producing Ltk+ cells, but died from the growth of Ltkf cells or from hypoglycemia [6]. Other types of experimental gene therapy trials have been attempted using liver cells with a liposome-Sendai virus gene transfer system or a retroviral system [23,24]. None of the gene therapy trials, however, utilized efficient, regulatable insulin expression systems.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulatable production of mature insulin from a hepatocyte cell line: insulin production is up‐regulated by cAMP and glucocorticoids, and down‐regulated by insulin

Hoshino

Takeuchi

1996

FEBS Letters

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We engineered a hepatoma cell line that produces an up-regulation of insulin in response to CAMP, dexamethasone, and retinoic acid, and a down-regulation in response to insulin. We devised a regulatory secretion system by placing proinsulin DNA under the regulatable promoter for phosphoenolpyruvate carboxykinase (PEPCK). To assess the ability to regulate insulin secretion, we used the rat hepatoma cell line, H4IIE. The H4IIE cells secreted immunoreactive insulin (IRI) constantly at a level of l-3 fmoll106 cells/h. IRI increased approximately two-fold upon stimulation with 0.5 mM CAMP and five-fold with the addition of the CAMP-dependent phosphodiesterase inhibitor IBMX, as compared to baseline IRI secretion. IRI increased 1% fold by l-500 nM dexamethasone together with CAMP and IBMX. Addition of exogenous insulin to the culture medium significantly decreased insulin mRNA expression on Northern blot.

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Section: A No Stimulantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulatable production of mature insulin from a hepatocyte cell line: insulin production is up‐regulated by cAMP and glucocorticoids, and down‐regulated by insulin

Hoshino

Takeuchi

1996

FEBS Letters

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“…[10][11][12]24 Briefly, phosphatidylserine, phosphatiin the basal cistern 2 days after 5 × 10 6 RSV-M glioma dylcholone, and cholesterol were mixed in a weight ratio cells were subcutaneously injected into the cisterna of 1:4.8:2. The lipid mixture (10 mg) was deposited on magna.…”

Section: Figure 5 Survival Curves Of Mg Mice Which Were Intrathecallymentioning

confidence: 99%

“…HVJ-liposomes may contain DNA, and over, meningeal dissemination, the invasion of glioma using this system foreign genes can be transferred very cells into the cerebrospinal fluid, is observed in 15% of efficiently ( Figure 1) and expressed ectopically in dividglioma patients at their terminal stages and may also play ing or nondividing mammalian cells in vivo. [10][11][12][13] To date, a role in the poor prognosis of patients. 2 there have been few applications of HVJ-liposomes to We have used the meningeal gliomatosis (MG) mouse tumor therapy.…”

mentioning

confidence: 99%

Gene delivery by HVJ-liposome in the experimental gene therapy of murine glioma

et al. 1997

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We investigated the delivery of foreign genes into mouse (MG) mouse model system. Highly efficient delivery was glioma cells in vivo using hemagglutinating virus of Japan observed in disseminated glioma cells, and 80% of MG (HVJ)-liposomes, which are coated by Sendai virus envelmice expressing the HSVtk gene were cured by treatment ope protein. HVJ-liposomes, containing lacZ gene or herwith ganciclovir. These results suggest that this novel gene pes simplex virus thymidine kinase (HSVtk) gene-bearing delivery system may be applicable for the in vivo gene therplasmid DNA were applied in the meningeal gliomatosis apy of human malignant glioma.Keywords: malignant glioma; gene transfer; HVJ-liposome; meningeal dissemination; MG mouseIt has been reported that intravenous administration of Introduction liposomes containing the rat insulin I gene resulted in Malignant glioma, especially glioblastoma, is one of the transient expression of rat insulin. 7 However, the most intractable tumors. Patients with glioblastoma have efficiency of liposomal fusion was low. The fusion a median survival of 9 months, despite intensive therapy efficiency was subsequently improved by using spike which may include surgery, irradiation, chemotherapy, proteins 8 or virus particles of HVJ. 9 HVJ-liposomes, and immunotherapy. 1 Poor prognosis is mainly due to which are coated by HVJ (Sendai virus) membranes, are invasion of glioma cells into the brain parenchyma. Morehighly fusigenic. HVJ-liposomes may contain DNA, and over, meningeal dissemination, the invasion of glioma using this system foreign genes can be transferred very cells into the cerebrospinal fluid, is observed in 15% of efficiently ( Figure 1) and expressed ectopically in dividglioma patients at their terminal stages and may also play ing or nondividing mammalian cells in vivo. [10][11][12][13] To date, a role in the poor prognosis of patients. 2 there have been few applications of HVJ-liposomes to We have used the meningeal gliomatosis (MG) mouse tumor therapy. In this study, HVJ-liposomes which conas a model system for patients with glioma. This model tain the lacZ gene or the HSVtk gene-bearing proviral system has been resistant to therapeutic intervention.DNA are applied in the MG mouse model, and we invesHowever, if 25% of stereotactically inoculated intratigate the efficacy of this delivery system for malignant cranial glioma cells are transduced with the herpes simglioma. plex virus type 1 thymidine kinase (HSVtk) gene, all mice can be cured by ganciclovir treatment. 3 Several methods exist for delivering foreign genes into somatic cells. Among them, retroviral vectors have been clinically one of the most frequently used. Because of low infectious titers, however, retroviruses have been used mainly for ex vivo gene delivery to hematopoietic stem cells, 4 or retrovirus-producing cells have been implanted in vivo as a source of continuous production. 5,6 Survival in the MG model could be prolonged by intrathecal administration of HSVtk-producing retrovirus packaging cell...

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“…Therefore, a major challenge to increase the level of transgene expression relies largely on improving the delivery of pDNA to the nucleus. Endosomal release, stabilization of pDNA within the cytoplasm, [66][67][68] and nuclear transport [69][70][71] are the major processes governing the efficiency of gene transfer.…”

Section: Level Of Transgene Expressionmentioning

confidence: 99%

Nonviral Approaches Satisfying Various Requirements for Effective in Vivo Gene Therapy.

Nishikawa

Hashida

2002

Biological & Pharmaceutical Bulletin

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Increased Expression of DNA Cointroduced with Nuclear Protein in Adult Rat Liver

Cited by 449 publications

References 27 publications

Regulatable production of mature insulin from a hepatocyte cell line: insulin production is up‐regulated by cAMP and glucocorticoids, and down‐regulated by insulin

Regulatable production of mature insulin from a hepatocyte cell line: insulin production is up‐regulated by cAMP and glucocorticoids, and down‐regulated by insulin

Gene delivery by HVJ-liposome in the experimental gene therapy of murine glioma

Nonviral Approaches Satisfying Various Requirements for Effective in Vivo Gene Therapy.

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