Direct intra-cardiomuscular transfer of β2-adrenergic receptor gene augments cardiac output in cardiomyopathic hamsters

Abstract

In chronic heart failure, down-regulation of ␤-adrenergic receptor (␤-AR) occurs in cardiomyocytes, resulting in low catecholamine response and impaired cardiac function. To correct the irregularity in the ␤-AR system, ␤-AR gene was transduced in vivo into failing cardiomyocytes. The EpsteinBarr virus (EBV)-based plasmid vector carrying human ␤ 2 -AR gene was injected into the left ventricular muscle of Bio14.6 cardiomyopathic hamsters whose ␤-AR is downregulated in the cardiomyocytes. The echocardiographic examinations revealed that stroke volume (SV) and cardiac output (CO) were significantly elevated at 2 to 4 days after

Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart

“…Although non-viral methods are free from virus-associated adverse effects, their transduction efficiency is low. For example, following direct intramyocardial injection of plasmid DNA into the heart of mice [3], rats [4,5], and hamsters [6], the transgenes were expressed only within a small area surrounding the injection site. A more efficient non-viral method of gene transfer is sonoporation of cells.…”

Highly efficient gene transfer into murine liver achieved by intravenous administration of naked Epstein–Barr virus (EBV)-based plasmid vectors

“…On the other hand, we have recently shown that naked EBV-based plasmid DNA was quite effective in transducing cardiac muscle. 22,29 When an EBV-based plasmid containing the ␤ 2 -adrenergic receptor gene was injected into the myocardium of cardiomyopathic hamsters, a significant elevation in cardiac output was obtained, suggesting a novel gene therapy strategy against heart failure. 22 The 'hydrodynamics-based procedure' may become an attractive approach for gene therapy of various diseases as well as functional, in vivo analysis of genes of interest.…”

“…[24][25][26][27] In some of these studies, the EBV-based plasmid vectors were combined with cationic liposomes, 25,28 cationic polymers, 23,[25][26][27]29 electroporation 21 or gene gun, 30 while in the other studies, naked EBV-based plasmid was injected into the cardiac muscle. 22,29 In the present study, we transferred the naked EBV-based plasmid vectors to the liver through the intravascular route.EBV-based and conventional plasmid vectors encoding the luciferase or ␤-gal genes as markers (Figure 1, upper panels) were constructed and injected intravenously into the tail vein of mice as described. 9 The injection with pG.GL3, a conventional luciferase-expression vector,…”

“…[18][19][20] Collectively, the EBVbased plasmid vector gives not only a prolonged, but also a stronger expression of the transgene. We have applied the EBV-plasmids to various preclinical studies of gene therapy, including those for hereditary, 21 chronic, 22,23 as well as malignant diseases. [24][25][26][27] In some of these studies, the EBV-based plasmid vectors were combined with cationic liposomes, 25,28 cationic polymers, 23,[25][26][27]29 electroporation 21 or gene gun, 30 while in the other studies, naked EBV-based plasmid was injected into the cardiac muscle.…”

“…[24][25][26][27] In some of these studies, the EBV-based plasmid vectors were combined with cationic liposomes, 25,28 cationic polymers, 23,[25][26][27]29 electroporation 21 or gene gun, 30 while in the other studies, naked EBV-based plasmid was injected into the cardiac muscle. 22,29 In the present study, we transferred the naked EBV-based plasmid vectors to the liver through the intravascular route.…”