Microvascular free tissue transfer for gene delivery: in vivo evaluation of different routes of plasmid and adenoviral delivery

Transfer of healthy autologous tissue as a microvascular free flap facilitates reconstruction during ablative cancer surgery. In addition to filling surgical defects, free flaps might concentrate viral vectors at the tumour bed and mediate local therapeutic effects. We evaluated the magnitude, topog...

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Veröffentlicht in:Gene therapy 2009-01, Vol.16 (1), p.78-92
Hauptverfasser: Agrawal, V K, Copeland, K M, Barbachano, Y, Rahim, A, Seth, R, White, C L, Hingorani, M, Nutting, C M, Kelly, M, Harris, P, Pandha, H, Melcher, A A, Vile, R G, Porter, C, Harrington, K J
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container_issue 1
container_start_page 78
container_title Gene therapy
container_volume 16
creator Agrawal, V K
Copeland, K M
Barbachano, Y
Rahim, A
Seth, R
White, C L
Hingorani, M
Nutting, C M
Kelly, M
Harris, P
Pandha, H
Melcher, A A
Vile, R G
Porter, C
Harrington, K J
description Transfer of healthy autologous tissue as a microvascular free flap facilitates reconstruction during ablative cancer surgery. In addition to filling surgical defects, free flaps might concentrate viral vectors at the tumour bed and mediate local therapeutic effects. We evaluated the magnitude, topography and duration of luciferase gene expression after plasmid and adenoviral delivery in rat superficial inferior epigastric (SIE) flaps. For plasmid delivery, luciferase expression was significantly increased by all transduction routes (topical, intraflap injection, intravascular) ( P
doi_str_mv 10.1038/gt.2008.140
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In addition to filling surgical defects, free flaps might concentrate viral vectors at the tumour bed and mediate local therapeutic effects. We evaluated the magnitude, topography and duration of luciferase gene expression after plasmid and adenoviral delivery in rat superficial inferior epigastric (SIE) flaps. For plasmid delivery, luciferase expression was significantly increased by all transduction routes (topical, intraflap injection, intravascular) ( P &lt;0.01) at day 1, but not at day 7. The spread of luciferase expression was significantly different between the 4 groups at 1 day ( P =0.026) and was greatest for flaps transduced by intravascular injection. For adenoviral transduction, total radiance was significantly different between the transduced groups at 1, 14 and 28 days ( P &lt;0.05 for all comparisons). The highest levels of radiance were seen in the intravascular group. There was a statistically significant difference in the spread of light emission between the 3 groups at 1 ( P =0.009) and 14 ( P =0.013) days, but this was no longer evident at 28 days. Intravascular adenoviral delivery yields high-level, diffuse and durable gene expression in rat SIE flaps and is suitable for examination in therapeutic models.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/gt.2008.140</identifier><identifier>PMID: 18784747</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adenoviridae - genetics ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Cancer ; Care and treatment ; Cell Biology ; Comparative studies ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Therapy ; Genetic aspects ; Genetic Therapy - methods ; Genetic transformation ; Genetic vectors ; Genetic Vectors - administration &amp; dosage ; Genetic Vectors - genetics ; Genetic Vectors - metabolism ; Health aspects ; Health. Pharmaceutical industry ; Human Genetics ; Industrial applications and implications. Economical aspects ; Injections ; Lac Operon ; Luciferases - analysis ; Luciferases - genetics ; Male ; Medical sciences ; Methods ; Models, Animal ; Nanotechnology ; original-article ; Plasmids - pharmacology ; Rats ; Rats, Inbred F344 ; Reverse Transcriptase Polymerase Chain Reaction ; Surgery ; Surgical Flaps ; Tissue Distribution ; Tissues ; Transduction, Genetic - methods ; Transfusions. Complications. Transfusion reactions. 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In addition to filling surgical defects, free flaps might concentrate viral vectors at the tumour bed and mediate local therapeutic effects. We evaluated the magnitude, topography and duration of luciferase gene expression after plasmid and adenoviral delivery in rat superficial inferior epigastric (SIE) flaps. For plasmid delivery, luciferase expression was significantly increased by all transduction routes (topical, intraflap injection, intravascular) ( P &lt;0.01) at day 1, but not at day 7. The spread of luciferase expression was significantly different between the 4 groups at 1 day ( P =0.026) and was greatest for flaps transduced by intravascular injection. For adenoviral transduction, total radiance was significantly different between the transduced groups at 1, 14 and 28 days ( P &lt;0.05 for all comparisons). The highest levels of radiance were seen in the intravascular group. 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Psychology</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Genetic aspects</subject><subject>Genetic Therapy - methods</subject><subject>Genetic transformation</subject><subject>Genetic vectors</subject><subject>Genetic Vectors - administration &amp; dosage</subject><subject>Genetic Vectors - genetics</subject><subject>Genetic Vectors - metabolism</subject><subject>Health aspects</subject><subject>Health. Pharmaceutical industry</subject><subject>Human Genetics</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Injections</subject><subject>Lac Operon</subject><subject>Luciferases - analysis</subject><subject>Luciferases - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methods</subject><subject>Models, Animal</subject><subject>Nanotechnology</subject><subject>original-article</subject><subject>Plasmids - pharmacology</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Surgery</subject><subject>Surgical Flaps</subject><subject>Tissue Distribution</subject><subject>Tissues</subject><subject>Transduction, Genetic - methods</subject><subject>Transfusions. Complications. Transfusion reactions. 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Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Comparative studies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Genetic aspects</topic><topic>Genetic Therapy - methods</topic><topic>Genetic transformation</topic><topic>Genetic vectors</topic><topic>Genetic Vectors - administration &amp; dosage</topic><topic>Genetic Vectors - genetics</topic><topic>Genetic Vectors - metabolism</topic><topic>Health aspects</topic><topic>Health. Pharmaceutical industry</topic><topic>Human Genetics</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Injections</topic><topic>Lac Operon</topic><topic>Luciferases - analysis</topic><topic>Luciferases - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methods</topic><topic>Models, Animal</topic><topic>Nanotechnology</topic><topic>original-article</topic><topic>Plasmids - pharmacology</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Surgery</topic><topic>Surgical Flaps</topic><topic>Tissue Distribution</topic><topic>Tissues</topic><topic>Transduction, Genetic - methods</topic><topic>Transfusions. Complications. Transfusion reactions. 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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Adenoviridae - genetics
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Applied cell therapy and gene therapy
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cancer
Care and treatment
Cell Biology
Comparative studies
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene Therapy
Genetic aspects
Genetic Therapy - methods
Genetic transformation
Genetic vectors
Genetic Vectors - administration & dosage
Genetic Vectors - genetics
Genetic Vectors - metabolism
Health aspects
Health. Pharmaceutical industry
Human Genetics
Industrial applications and implications. Economical aspects
Injections
Lac Operon
Luciferases - analysis
Luciferases - genetics
Male
Medical sciences
Methods
Models, Animal
Nanotechnology
original-article
Plasmids - pharmacology
Rats
Rats, Inbred F344
Reverse Transcriptase Polymerase Chain Reaction
Surgery
Surgical Flaps
Tissue Distribution
Tissues
Transduction, Genetic - methods
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
title Microvascular free tissue transfer for gene delivery: in vivo evaluation of different routes of plasmid and adenoviral delivery
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