A designed curved DNA sequence remarkably enhances transgene expression from plasmid DNA in mouse liver

The intranuclear disposition of plasmid DNA is extremely important for transgene expression. The interactions between the plasmid DNA and the histone proteins are one of the keys for controlling the disposition. In this study, the effects of a left-handedly curved sequence (20–40 repeated A•T tracts...

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Veröffentlicht in:Gene therapy 2012-08, Vol.19 (8), p.828-835
Hauptverfasser: Fukunaga, S, Kanda, G, Tanase, J, Harashima, H, Ohyama, T, Kamiya, H
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container_issue 8
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container_title Gene therapy
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creator Fukunaga, S
Kanda, G
Tanase, J
Harashima, H
Ohyama, T
Kamiya, H
description The intranuclear disposition of plasmid DNA is extremely important for transgene expression. The interactions between the plasmid DNA and the histone proteins are one of the keys for controlling the disposition. In this study, the effects of a left-handedly curved sequence (20–40 repeated A•T tracts) on transgene expression from a plasmid were examined in vivo . A naked luciferase plasmid with the curved sequence was delivered into mouse liver by a hydrodynamics-based injection, and the luciferase activities were quantitated at various time points. Interestingly, transgene expression was markedly increased by the addition of the curved sequence. An analysis of the nucleosome positions near the left-handedly curved sequence suggested that the sequence functions as an acceptor of the histone core and allows nucleosome sliding, resulting in transcriptional activation. These results suggested that the designed curved DNA sequences could control transgene expression from plasmid DNAs in vivo .
doi_str_mv 10.1038/gt.2011.127
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The interactions between the plasmid DNA and the histone proteins are one of the keys for controlling the disposition. In this study, the effects of a left-handedly curved sequence (20–40 repeated A•T tracts) on transgene expression from a plasmid were examined in vivo . A naked luciferase plasmid with the curved sequence was delivered into mouse liver by a hydrodynamics-based injection, and the luciferase activities were quantitated at various time points. Interestingly, transgene expression was markedly increased by the addition of the curved sequence. An analysis of the nucleosome positions near the left-handedly curved sequence suggested that the sequence functions as an acceptor of the histone core and allows nucleosome sliding, resulting in transcriptional activation. 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identifier ISSN: 0969-7128
ispartof Gene therapy, 2012-08, Vol.19 (8), p.828-835
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1476-5462
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subjects 631/1647/1511
631/208/199
631/337/100/1701
Analysis
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Applied cell therapy and gene therapy
Base Sequence
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cell Biology
Cell Nucleus - metabolism
Chromatin. Chromosome
Deoxyribonucleic acid
Disposition
DNA
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene Therapy
Genetic aspects
Handedness
Health. Pharmaceutical industry
Histones
Histones - metabolism
Human Genetics
Industrial applications and implications. Economical aspects
Keys
Liver
Liver - metabolism
Male
Medical sciences
Mice
Mice, Inbred BALB C
Molecular and cellular biology
Molecular genetics
Nanotechnology
Nucleosomes
Nucleosomes - genetics
Nucleotide sequence
original-article
Physiological aspects
Plasmids
Plasmids - genetics
Rodents
Transcription activation
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Transgenes
title A designed curved DNA sequence remarkably enhances transgene expression from plasmid DNA in mouse liver
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