Minicircle DNA provide enhanced and prolonged transgene expression following airway gene transfer

Munye, Mustafa M., Tagalakis, Aristides, Barnes, Josephine L., Brown, Rachel E., McAnulty, Robin J., Howe, Steven J. and Hart, Stephen L. (2016) Minicircle DNA provide enhanced and prolonged transgene expression following airway gene transfer. Scientific Reports, 6. p. 23125. ISSN 2045-2322 DOI

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Gene therapy for cystic fibrosis using non-viral, plasmid-based formulations has been the subject of intensive research for over two decades but a clinically viable product has yet to materialise in large part due to inefficient transgene expression. Minicircle DNA give enhanced and more persistent transgene expression compared to plasmid DNA in a number of organ systems but has not been assessed in the lung. In this study we compared minicircle DNA with plasmid DNA in transfections of airway epithelial cells. In vitro, luciferase gene expression from minicircles was 5-10-fold higher than with plasmid DNA. In eGFP transfections in vitro both the mean fluorescence intensity and percentage of cells transfected was 2-4-fold higher with minicircle DNA. Administration of equimolar amounts of DNA to mouse lungs resulted in a reduced inflammatory response and more persistent transgene expression, with luciferase activity persisting for 2 weeks from minicircle DNA compared to plasmid formulations. Transfection of equal mass amounts of DNA in mouse lungs resulted in a 6-fold increase in transgene expression in addition to more persistent transgene expression. Our findings have clear implications for gene therapy of airway disorders where plasmid DNA transfections have so far proven inefficient in clinical trials.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Divisions: Biology
Date Deposited: 19 Apr 2018 12:18

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