Feline Neural Progenitor Cells II: Use of Novel Plasmid Vector and Hybrid Promoter to Drive Expression of Glial Cell Line-Derived Neurotrophic Factor Transgene

Sustained transgene expression is required for the success of cell transplant-based gene therapy. Most widely used are lentiviral-based vectors which integrate into the host genome and thereby maintain sustained transgene expression. This requires integration into the nuclear genome, and potential r...

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Main Authors: X. Joann You, Jing Yang, Ping Gu, Chee Gee Liew, Henry J. Klassen
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2012/604982
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author X. Joann You
Jing Yang
Ping Gu
Chee Gee Liew
Henry J. Klassen
author_facet X. Joann You
Jing Yang
Ping Gu
Chee Gee Liew
Henry J. Klassen
author_sort X. Joann You
collection DOAJ
description Sustained transgene expression is required for the success of cell transplant-based gene therapy. Most widely used are lentiviral-based vectors which integrate into the host genome and thereby maintain sustained transgene expression. This requires integration into the nuclear genome, and potential risks include activation of oncogenes and inactivation of tumor suppressor genes. Plasmids have been used; however lack of sustained expression presents an additional challenge. Here we used the pCAG-PyF101-eGFP plasmid to deliver the human GDNF gene to cat neural progenitor cells (cNPCs). This vector consists of a CAGG composite promoter linked to the polyoma virus mutant enhancer PyF101. Expression of an episomal eGFP reporter and GDNF transgene were stably maintained by the cells, even following induction of differentiation. These genetically modified cells appear suitable for use in allogeneic models of cell-based delivery of GDNF in the cat and may find veterinary applications should such strategies prove clinically beneficial.
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institution Kabale University
issn 1687-966X
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spelling doaj-art-e9ba45a966f74cdfa5288b99d24e6e202025-08-20T03:26:34ZengWileyStem Cells International1687-966X1687-96782012-01-01201210.1155/2012/604982604982Feline Neural Progenitor Cells II: Use of Novel Plasmid Vector and Hybrid Promoter to Drive Expression of Glial Cell Line-Derived Neurotrophic Factor TransgeneX. Joann You0Jing Yang1Ping Gu2Chee Gee Liew3Henry J. Klassen4The Gavin Herbert Eye Institute, School of Medicine, University of California, Irvine, Hewitt Hall, Rm. 2014, 843 Health Sciences Road, Irvine, CA 92697-1705, USAThe Gavin Herbert Eye Institute, School of Medicine, University of California, Irvine, Hewitt Hall, Rm. 2014, 843 Health Sciences Road, Irvine, CA 92697-1705, USAThe Gavin Herbert Eye Institute, School of Medicine, University of California, Irvine, Hewitt Hall, Rm. 2014, 843 Health Sciences Road, Irvine, CA 92697-1705, USAStem Cell Center, Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, CA 92521, USAThe Gavin Herbert Eye Institute, School of Medicine, University of California, Irvine, Hewitt Hall, Rm. 2014, 843 Health Sciences Road, Irvine, CA 92697-1705, USASustained transgene expression is required for the success of cell transplant-based gene therapy. Most widely used are lentiviral-based vectors which integrate into the host genome and thereby maintain sustained transgene expression. This requires integration into the nuclear genome, and potential risks include activation of oncogenes and inactivation of tumor suppressor genes. Plasmids have been used; however lack of sustained expression presents an additional challenge. Here we used the pCAG-PyF101-eGFP plasmid to deliver the human GDNF gene to cat neural progenitor cells (cNPCs). This vector consists of a CAGG composite promoter linked to the polyoma virus mutant enhancer PyF101. Expression of an episomal eGFP reporter and GDNF transgene were stably maintained by the cells, even following induction of differentiation. These genetically modified cells appear suitable for use in allogeneic models of cell-based delivery of GDNF in the cat and may find veterinary applications should such strategies prove clinically beneficial.http://dx.doi.org/10.1155/2012/604982
spellingShingle X. Joann You
Jing Yang
Ping Gu
Chee Gee Liew
Henry J. Klassen
Feline Neural Progenitor Cells II: Use of Novel Plasmid Vector and Hybrid Promoter to Drive Expression of Glial Cell Line-Derived Neurotrophic Factor Transgene
Stem Cells International
title Feline Neural Progenitor Cells II: Use of Novel Plasmid Vector and Hybrid Promoter to Drive Expression of Glial Cell Line-Derived Neurotrophic Factor Transgene
title_full Feline Neural Progenitor Cells II: Use of Novel Plasmid Vector and Hybrid Promoter to Drive Expression of Glial Cell Line-Derived Neurotrophic Factor Transgene
title_fullStr Feline Neural Progenitor Cells II: Use of Novel Plasmid Vector and Hybrid Promoter to Drive Expression of Glial Cell Line-Derived Neurotrophic Factor Transgene
title_full_unstemmed Feline Neural Progenitor Cells II: Use of Novel Plasmid Vector and Hybrid Promoter to Drive Expression of Glial Cell Line-Derived Neurotrophic Factor Transgene
title_short Feline Neural Progenitor Cells II: Use of Novel Plasmid Vector and Hybrid Promoter to Drive Expression of Glial Cell Line-Derived Neurotrophic Factor Transgene
title_sort feline neural progenitor cells ii use of novel plasmid vector and hybrid promoter to drive expression of glial cell line derived neurotrophic factor transgene
url http://dx.doi.org/10.1155/2012/604982
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