Dachs, G.U., Coralli, C., Hart, S.L. et al. (1 more author) (2000) Gene delivery to hypoxic cells in vitro. British Journal of Cancer , 83 (5). pp. 662-667. ISSN 0007-0920
Abstract
Hypoxia in solid tumours has been correlated with poor prognosis and resistance to radiation and chemotherapy. Hypoxia is also a strong stimulus for gene expression. We previously proposed a gene therapy approach which exploits the presence of severe hypoxia in tumours for the induction of therapeutic genes. Hypoxic cells are known to have a reduced metabolic rate, transcription and translation. These facts may prevent gene transfer and therefore warranted further investigation. In this paper the feasibility of gene delivery in vitro under tumour conditions was demonstrated. DNA was delivered in vitro using a peptide-mediated non-viral system. Across a range of oxygen tensions and mammalian cell lines (including human tumour and endothelial cells) it was shown that hypoxic cells could be transfected. Transfection efficiencies varied depending on the level of hypoxia, cell characteristics and gene promoters used. An in vitro model of hypoxia/reoxygenation, designed to mimic the variable nature of tumour hypoxia, showed that hypoxic preconditioning and reoxygenation alone did not reduce transfection efficiency significantly; only chronic anoxia reduced transfection. The fact that neither intermediate hypoxia nor intermittent anoxia significantly reduced transfection is promising for future hypoxia-targeted gene therapy strategies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2000 Cancer Research Campaign. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
Keywords: | green fluorescent protein; tumour conditions; anoxia; BLADDER-CARCINOMA; SOLID TUMORS; LINE; EXPRESSION; PROTEINS; OXYGENATION; METASTASES; CANCERS; FLUX |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 18 May 2017 09:20 |
Last Modified: | 18 May 2017 09:20 |
Published Version: | https://doi.org/ 10.1054/bjoc.2000.1318 |
Status: | Published |
Publisher: | Cancer Research UK |
Refereed: | Yes |
Identification Number: | 10.1054/bjoc.2000.1318 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115373 |
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