Nonsurgical direct delivery of plasmid DNA into rat heart: time course, dose response, and the influence of different promoters on gene expression.
Transfer of genes encoding therapeutic proteins into the myocardium shows great potential for treatment of coronary artery disease. To quantitatively elucidate the behavior of plasmid DNA following cardiac gene transfer, time kinetics, dose-response relationship, systemic spread to the liver, and the influence of different promoters on plasmid DNA gene expression in rat hearts were examined using a novel nonsurgical direct delivery method that enables testing of large numbers of animals. Plasmids encoding either vascular endothelial growth factor A 165 or a fusion protein between enhanced green fluorescent protein (EGFP) luciferase were injected directly in rat hearts under echocardiographic guidance. The results show that gene expression is dose related and that the duration of gene expression is transient. These findings underscore the necessity to explore other efficient vectors or alternative methods of gene delivery to achieve increased and prolonged gene expression.
Sarkar
Nondita
N
Department of Cardiology, Huddinge University Hospital, Stockholm, Sweden.
Blomberg
Pontus
P
Wärdell
Eva
E
Eskandarpour
Malihe
M
Sylvén
Christer
C
Drvota
Viktor
V
Islam
Khalid B
KB
D000818:Animals; D019556:COS Cells; D003587:Cytomegalovirus / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D007267:Injections; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000235:genetics; D010957:Plasmids / Q000008:administration & dosage; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008164:Luminescent Proteins; D008222:Lymphokines; D020648:Peptide Elongation Factor 1; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D049452:Green Fluorescent Proteins; D008156:Luciferases