Visualization of the transgene distribution according to the administration route allows prediction of the transfection efficacy and validation of the results obtained

Gene transfer to the lung can be achieved via a systemic, that targets the endothelium, or local, that targets the epithelium, delivery route. In the present study, we followed the distribution of a plasmid after transfection using some of our phosphonolipids, which have previously shown their effic...

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Veröffentlicht in:Gene therapy 2002-06, Vol.9 (11), p.736-739
Hauptverfasser: DELEPINE, P, MONTIER, T, GUILLAUME, C, VAYSSE, L, LE PAPE, A, FEREC, C
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container_end_page 739
container_issue 11
container_start_page 736
container_title Gene therapy
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creator DELEPINE, P
MONTIER, T
GUILLAUME, C
VAYSSE, L
LE PAPE, A
FEREC, C
description Gene transfer to the lung can be achieved via a systemic, that targets the endothelium, or local, that targets the epithelium, delivery route. In the present study, we followed the distribution of a plasmid after transfection using some of our phosphonolipids, which have previously shown their efficiency in transfecting mouse lungs. The plasmid was radiolabeled and varying combinations of plasmid/phosphonolipid were administered by intravenous injection, or by endotracheal spray. The distribution of radioactive labeling was observed over a time course using a gamma-camera. These images were then correlated with the results for luciferase expression levels in the lungs. In each case, lungs were well targeted. However, whereas an intravenous injection reaches all of the lung immediately, progressive diffusion occurs when the plasmid/phosphonolipid is administered via an aerosol. Elimination of the radioactivity associated with plasmid occurs via the urinary tract after intravenous injections, and via the feces using the aerosol delivery approach. The radioactivity detected in the lungs correlated strongly with transgene expression. Thus, such an imaging technique is a powerful strategy to predict the formulation that will generate the best transfection efficiency. This study reveals that scintigraphic imaging permits both validation of the administration method and the results obtained for each animal, thereby reducing the statistical variability of in vivo experiments.
doi_str_mv 10.1038/sj.gt.3301742
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Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biological Transport ; Biotechnology ; Cystic Fibrosis - therapy ; Endothelium ; Epithelium ; Fundamental and applied biological sciences. Psychology ; Gamma Cameras ; Gene Expression ; Gene therapy ; Gene transfer ; Genetic Markers ; Genetic Therapy - methods ; Health. Pharmaceutical industry ; Industrial applications and implications. Economical aspects ; Injection ; Injections, Intravenous ; Intravenous administration ; Luciferases - genetics ; Lung ; Lungs ; Medical sciences ; Mice ; Phosphonolipids ; Plasmids ; Radioactive labeling ; Radioactivity ; Transfection ; Transfection - methods ; Transfusions. Complications. Transfusion reactions. 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In the present study, we followed the distribution of a plasmid after transfection using some of our phosphonolipids, which have previously shown their efficiency in transfecting mouse lungs. The plasmid was radiolabeled and varying combinations of plasmid/phosphonolipid were administered by intravenous injection, or by endotracheal spray. The distribution of radioactive labeling was observed over a time course using a gamma-camera. These images were then correlated with the results for luciferase expression levels in the lungs. In each case, lungs were well targeted. However, whereas an intravenous injection reaches all of the lung immediately, progressive diffusion occurs when the plasmid/phosphonolipid is administered via an aerosol. Elimination of the radioactivity associated with plasmid occurs via the urinary tract after intravenous injections, and via the feces using the aerosol delivery approach. 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Psychology</subject><subject>Gamma Cameras</subject><subject>Gene Expression</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Genetic Markers</subject><subject>Genetic Therapy - methods</subject><subject>Health. Pharmaceutical industry</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Injection</subject><subject>Injections, Intravenous</subject><subject>Intravenous administration</subject><subject>Luciferases - genetics</subject><subject>Lung</subject><subject>Lungs</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Phosphonolipids</subject><subject>Plasmids</subject><subject>Radioactive labeling</subject><subject>Radioactivity</subject><subject>Transfection</subject><subject>Transfection - methods</subject><subject>Transfusions. Complications. Transfusion reactions. 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subjects Aerosols
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Applied cell therapy and gene therapy
Biological and medical sciences
Biological Transport
Biotechnology
Cystic Fibrosis - therapy
Endothelium
Epithelium
Fundamental and applied biological sciences. Psychology
Gamma Cameras
Gene Expression
Gene therapy
Gene transfer
Genetic Markers
Genetic Therapy - methods
Health. Pharmaceutical industry
Industrial applications and implications. Economical aspects
Injection
Injections, Intravenous
Intravenous administration
Luciferases - genetics
Lung
Lungs
Medical sciences
Mice
Phosphonolipids
Plasmids
Radioactive labeling
Radioactivity
Transfection
Transfection - methods
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Transgenes
Urinary tract
title Visualization of the transgene distribution according to the administration route allows prediction of the transfection efficacy and validation of the results obtained
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