Publications
55 results found
Themis M, May D, Coutelle C, et al., 2003, Mutational effects of retrovirus insertion on the genome of V79 cells by an attenuated retrovirus vector: implications for gene therapy, GENE THERAPY, Vol: 10, Pages: 1703-1711, ISSN: 0969-7128
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- Citations: 13
David AL, Peebles DM, Gregory L, et al., 2003, Percutaneous ultrasound-guided injection of the trachea in fetal sheep: A novel technique to target the fetal airways, FETAL DIAGNOSIS AND THERAPY, Vol: 18, Pages: 385-390, ISSN: 1015-3837
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- Citations: 17
Waddington SN, Mitrophanous KA, Ellard FM, et al., 2003, Long-term transgene expression by administration of a lentivirus-based vector to the fetal circulation of immuno-competent mice, GENE THERAPY, Vol: 10, Pages: 1234-1240, ISSN: 0969-7128
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- Citations: 52
David A, Cook T, Waddington S, et al., 2003, Ultrasound-guided percutaneous delivery of adenoviral vectors encoding the β-galactosidase and human factor IX genes to early gestation fetal sheep <i>in utero</i>, HUMAN GENE THERAPY, Vol: 14, Pages: 353-364, ISSN: 1043-0342
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- Citations: 45
Waddington SN, Buckley SMK, Nivsarkar M, et al., 2003, In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor, BLOOD, Vol: 101, Pages: 1359-1366, ISSN: 0006-4971
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- Citations: 85
Gregory LG, Harbottle RP, Lawrence L, et al., 2003, Enhancement of adenovirus-mediated gene transfer to the airways by DEAE dextran and sodium caprate <i>in vivo</i>, MOLECULAR THERAPY, Vol: 7, Pages: 19-26, ISSN: 1525-0016
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- Citations: 49
Selden C, Casbard A, Themis M, et al., 2003, Characterization of long-term survival of syngeneic hepatocytes in rat peritoneum., Cell Transplant, Vol: 12, Pages: 569-578, ISSN: 0963-6897
Hepatocyte transplantation is a potential therapy for both acute and chronic hepatic insufficiency and also for treatment of inborn errors of metabolism affecting the liver. The peritoneum is one site for implantation and has several advantages: cells implanted there can be easily identified and observed, and it has a relatively large capacity. Long-term survival using "pure" hepatocytes in the peritoneum have been disappointing. We hypothesized that cotransplantation of hepatocytes with nonparenchymal cells would help maintain differentiated hepatocyte function. Rat liver cells transplanted intraperitoneally into August rats were sacrificed at 7 days, 1, 3, 6, 9, and 12 months and analyzed for presence, basal proliferation, and functionality of hepatocytes. To demonstrate that ectopic hepatocytes remained susceptible to exogenous growth factors affecting cell proliferation, rats 9 and 12 months after transplantation were stimulated with tri-iodothyronine and KGF. Hepatocytes were identified 7 days to >12 months, by H&E and immunohistochemically, as ectopic islands in the omental fat. Functionality was confirmed by glycogen deposition. Basal proliferation in 7-day rats was 28.0 +/- 10/1000 hepatocytes in ectopic islands (cf. 5.70 +/- 2.7/1000 in recipient liver). Proliferation in ectopic islands was greater than host liver. Growth factor-stimulated proliferation in ectopic islands induced a 70-fold increase in DNA synthesis. In conclusion, hepatocytes transplanted with nonparenchymal cells survive, proliferate, and function in the peritoneum of normal rats, and respond to exogenous growth stimuli. Their survival and proliferation in the presence of a normal functioning liver has implications for the potential use of the peritoneal site clinically for supplementation of liver function in metabolic disorders.
Eden ER, Patel DD, Sun XM, et al., 2002, Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1, JOURNAL OF CLINICAL INVESTIGATION, Vol: 110, Pages: 1695-1702, ISSN: 0021-9738
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- Citations: 66
Chan LMC, Coutelle C, Themis M, 2001, A novel human suspension culture packaging cell line for production of high-titre retroviral vectors, GENE THERAPY, Vol: 8, Pages: 697-703, ISSN: 0969-7128
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- Citations: 12
Coutelle C, Themis M, Schneider H, et al., 2001, Fetal somatic gene therapy - A preventive approach to the treatment of genetic disease: The case for, STEM CELLS FORM CORD BLOOD, IN UTERO STEM CELL DEVELOPMENT, AND TRANSPLANTATION-INCLUSIVE GENE THERAPY, Vol: 33, Pages: 99-114, ISSN: 0947-6075
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- Citations: 3
Coutelle C, Themis M, Schneider H, et al., 2001, Fetal somatic gene therapy - a preventive approach to the treatment of genetic disease: the case for, Pages: 99-114, ISBN: 9783540677017
David AL, Themis M, Cook T, et al., 2001, Fetal gene therapy, Ultrasound Rev Obstet Gynecol, Vol: 1, Pages: 14-27, ISSN: 1472-2240
Schneider H, Groves M, Mühle C, et al., 2000, Retargeting of adenoviral vectors to neurons using the H<sub>c</sub> fragment of tetanus toxin, GENE THERAPY, Vol: 7, Pages: 1584-1592, ISSN: 0969-7128
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- Citations: 22
Forbes SJ, Themis M, Alison MR, et al., 2000, Tri-iodothyronine and a deleted form of hepatocyte growth factor act synergistically to enhance liver proliferation and enable in vivo retroviral gene transfer via the peripheral venous system, GENE THERAPY, Vol: 7, Pages: 784-789, ISSN: 0969-7128
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- Citations: 15
McKay TR, MacVinish LJ, Carpenter B, et al., 2000, Selective in vivo transfection of murine biliary epithelia using polycation-enhanced adenovirus, GENE THERAPY, Vol: 7, Pages: 644-652, ISSN: 0969-7128
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- Citations: 12
Forbes SJ, Themis M, Alison MR, et al., 2000, Synergistic growth factors enhance rat liver proliferation and enable retroviral gene transfer via a peripheral vein, GASTROENTEROLOGY, Vol: 118, Pages: 591-598, ISSN: 0016-5085
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- Citations: 22
Themis M, Schneider H, Kiserud T, et al., 1999, Successful expression of β-galactosidase and factor IX transgenes in fetal and neonatal sheep after ultrasound-guided percutaneous adenovirus vector administration into the umbilical vein, GENE THERAPY, Vol: 6, Pages: 1239-1248, ISSN: 0969-7128
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- Citations: 59
Schneider H, Adebakin S, Themis M, et al., 1999, Therapeutic plasma concentrations of human factor IX in mice after gene delivery into the amniotic cavity: A model for the prenatal treatment of haemophilia B, JOURNAL OF GENE MEDICINE, Vol: 1, Pages: 424-432, ISSN: 1099-498X
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- Citations: 34
Forbes SJ, Themis M, Alison MR, et al., 1998, Retroviral gene transfer to the liver in vivo during tri-iodothyronine induced hyperplasia, GENE THERAPY, Vol: 5, Pages: 552-555, ISSN: 0969-7128
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- Citations: 31
Themis M, Forbes SJ, Chan L, et al., 1998, Enhanced in vitro and in vivo gene delivery using cationic agent complexed retrovirus vectors, Gene Therapy, Vol: 5, Pages: 1180-1186, ISSN: 0969-7128
Douar AM, Adebakin S, Themis M, et al., 1997, Foetal gene delivery in mice by intra-amniotic administration of retroviral producer cells and adenovirus, GENE THERAPY, Vol: 4, Pages: 883-890, ISSN: 0969-7128
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- Citations: 65
Douar AM, Themis M, Sandig V, et al., 1996, Effect of amniotic fluid on cationic lipid mediated transfection and retroviral infection, GENE THERAPY, Vol: 3, Pages: 789-796, ISSN: 0969-7128
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- Citations: 21
Douar AM, Themis M, Coutelle C, 1996, Fetal somatic gene therapy., Mol Hum Reprod, Vol: 2, Pages: 633-641, ISSN: 1360-9947
Fetal somatic gene therapy is emerging as a new experimental approach, in particular to prevent irreversible perinatal disease manifestation for many inherited conditions. Early therapeutic gene application may also allow targeting of still expanding stem cell populations of organ or cell systems inaccessible later in life and help to avoid immune sensitization against the therapeutic vector system or transgene protein product. The progress in development of ultrasound scanning and embryofetoscopy over the last decade has made minimally invasive administration of therapeutic gene transfer vectors to the fetus in utero possible in principle. We review here the different considerations in choosing candidate diseases, the possible routes of administration and times in fetal development for application of a therapeutic gene and discuss the benefits and problems of present vector systems in this context. Given the many unknown aspects of fetal gene transfer, it is essential to extensively investigate this new approach to gene therapy in animal models for specific diseases, to improve on the technology of delivery and to assess efficacy of expression as well as the possible side effects before application to humans can be considered.
Trott DA, Cuthbert AP, Todd CM, et al., 1995, Novel use of a selectable fusion gene as an "in-out" marker for studying genetic loss in mammalian cells., Mol Carcinog, Vol: 12, Pages: 213-224, ISSN: 0899-1987
Recent demonstrations of loss of heterozygosity in a wide variety of human cancers suggest that large multilocus genetic deletions (presumably including tumor suppressor genes) constitute a major class of genetic alteration in human carcinogenesis. Here we show that a bifunctional fusion gene (Hytk), suitable for both positive and negative selection, is an effective marker for studying genetic loss in mammalian cells with minimal interference from point-mutational changes. Studies with a transgenic V79 cell line in which a single functional copy of Hytk was stably inserted into the genome in a retroviral vector showed that loss of the marker (and presumably flanking cellular genetic material) could be induced efficiently by ionizing radiation (gamma-rays and fast neutrons) but only weakly by the powerful point-mutagen benzo[a]pyrene diol epoxide. In a first application of the system, we provide evidence that radiation-induced loss can occur through an indirect mechanism after a high-frequency event. Collectively, our results suggest that the Hytk marker should be a valuable tool for studying genome position effects on the tolerance of genetic loss in cultured human cells that represent different stages in clonal evolution and tumor progression.
Cuthbert AP, Trott DA, Ekong RM, et al., 1995, Construction and characterization of a highly stable human: rodent monochromosomal hybrid panel for genetic complementation and genome mapping studies., Cytogenet Cell Genet, Vol: 71, Pages: 68-76, ISSN: 0301-0171
Human:rodent somatic cell hybrids carrying a single, intact, selectable human chromosome are valuable both for functional somatic cell genetic analysis and genome mapping procedures. Here, we describe the construction and detailed molecular cytogenetic characterization of a panel of 23 stable hybrids, representing all 22 human autosomes plus the X-chromosome. Individual normal human chromosomes have been tagged with a selectable fusion gene (Hytk) introduced into the chromosome in a small (4.2 kbp) retroviral vector. Use of the Hytk marker permits both positive and negative ("in-out") selection to be applied to the human chromosome in any mammalian cell background. The panel includes 18 new hybrids isolated by direct microcell transfer from normal human diploid fibroblasts into mouse A9 cells.
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