Phosphodiesterase Inhibitor-mediated Potentiation of Adenovirus Delivery to Myocardium

Nagata, Kôichi; Marbán, Eduardo; Lawrence, John H.; Donahue, Kevin

doi:10.1006/jmcc.2000.1322

Cited by 46 publications

(43 citation statements)

References 10 publications

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“…The improvement in the method of gene delivery to obtain a selective, homogeneous, and highly efficient gene transduction has extensively contributed to the advancement in gene therapy, especially when a large target area was involved. [9][10][11][12][13][14] …”

Section: Introductionmentioning

confidence: 99%

Gene Therapy for Cardiac Arrhythmias

Donahue

Kikuchi

Sasano

2005

Trends in Cardiovascular Medicine

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Section: Introductionmentioning

confidence: 99%

Gene Therapy for Cardiac Arrhythmias

Donahue

Kikuchi

Sasano

2005

Trends in Cardiovascular Medicine

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“…To achieve this, we chose mid-range levels of several factors previously shown to play roles in either the ex vivo or the small mammal in vivo environment [11][12][13]18,19]. Intracoronary pretreatment and virus solutions were delivered to the mid-LAD, immediately after the second diagonal branch ( Figure 1A).…”

Section: Baselinementioning

confidence: 99%

“…We previously reported the role of several parameters relevant to gene transfer efficiency in rabbit ex vivo and in vitro models [11][12][13]. The goal of the current report was to build an effective myocardial gene transfer method by sequentially exploring these variables in the large mammal in vivo environment.…”

Section: Introductionmentioning

confidence: 99%

Targeted high-efficiency, homogeneous myocardial gene transfer

Sasano

Kikuchi

McDonald

et al. 2007

Journal of Molecular and Cellular Cardiology

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Objective-Myocardial gene therapy continues to show promise as a tool for investigation and treatment of cardiac disease. Progress toward clinical approval has been slowed by limited in vivo delivery methods. We investigated the problem in a porcine model, with an objective of developing a method for high efficiency, homogeneous myocardial gene transfer that could be used in large mammals, and ultimately in humans.Methods-Eighty-one piglets underwent coronary catheterization for delivery of viral vectors into the left anterior descending artery and/or the great cardiac vein. The animals were followed for 5 or 28 days, and then transgene efficiency was quantified from histological samples. Results-The baseline protocol included treatment with VEGF, nitroglycerin, and adenosine followed by adenovirus infusion into the LAD. Gene transfer efficiency varied with choice of viral vector, with use of VEGF, adenosine, or nitroglycerin, and with calcium concentration. The best results were obtained by manipulation of physical parameters. Simultaneous infusion of adenovirus through both left anterior descending artery and great cardiac vein resulted in gene transfer to 78 ± 6% of myocytes in a larger target area. This method was well tolerated by the animals. Conclusions-We demonstrate targeted, homogeneous, high efficiency gene transfer using a method that should be transferable for eventual human usage.

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“…18 Also note that ACh -used to induce cardiac arrest in the present study -is known to be able to trigger the release of endogenous NO, leading to the increase of vascular permeability via the cGMP cascade. 19 Moreover, the replacement of the blood by a crystalloid solution may also have enhanced vascular permeability. 17 Using our protocol to block the aortic outflow and the right atrial inflow, we were able to mimic under closechest conditions the protocol previously developed by Hajjar et al 7 These authors used cross-clamping of the aorta and the pulmonary artery to perform adenoviral transfection under HIP.…”

Section: Optimization Of Gene Deliverymentioning

confidence: 99%

A minimally invasive approach for efficient gene delivery to rodent hearts

et al. 2004

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Transcoronary gene delivery represents a desirable option to achieve global myocardial transgene expression but still requires aggressive surgical preparation in rodents. We therefore developed a catheter-based approach for cardiac gene transfer in the closed chest rat. A double-lumen balloon catheter was used to create aortic occlusion for specific infusion of adenoviral vectors carrying a b-galactosidase transgene (1 Â 10 11 PFU) into the coronaries. Simultaneously, venous return was obstructed by a second balloon catheter in the right atrium. To prolong viral incubation time, we induced a transient cardiac arrest (2 and 5 min) by a combination of acetylcholine and the b-receptor antagonist, esmolol. At 72 h after transfection, the hearts showed a homogeneous and widespread b-galactosidase expression, and the transduction efficiency increased and up to about 43% of cardiac myocytes (histochemistry) with a 400-fold increase of b-galactosidase activity (luminescence assay) compared to sham-operated hearts. Pharmacological treatment aimed at increasing vascular permeability (SNAP and histamine) did not bring about synergistic effects on transfection efficiency. In addition, the method using high intracoronary pressure delivery (4300 mmHg) in a singlepass manner resulted in rather sparse b-galactosidase expression in the myocardium (3-5% of cardiac myocytes). Therefore, the percutaneous gene delivery system described here provides a simple and minimally invasive procedure that represents a novel strategy for a homogeneous and highly efficient in vivo gene transfer to rodent hearts. Our results also suggest that prolongation of viral incubation time is an effective means for achieving highly efficient myocardial gene transduction.

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Phosphodiesterase Inhibitor-mediated Potentiation of Adenovirus Delivery to Myocardium

Cited by 46 publications

References 10 publications

Gene Therapy for Cardiac Arrhythmias

Gene Therapy for Cardiac Arrhythmias

Targeted high-efficiency, homogeneous myocardial gene transfer

A minimally invasive approach for efficient gene delivery to rodent hearts

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