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A minimally invasive approach for efficient gene delivery to rodent hearts

Gene Therapy volume 11, pages 260–265 (2004)Cite this article

Abstract

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 β-galactosidase transgene (1 × 1011 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 β-receptor antagonist, esmolol. At 72 h after transfection, the hearts showed a homogeneous and widespread β-galactosidase expression, and the transduction efficiency increased and up to about 43% of cardiac myocytes (histochemistry) with a 400-fold increase of β-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 (>300 mmHg) in a single-pass manner resulted in rather sparse β-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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Acknowledgements

This work was supported by grant 9772136 from the Forschungskommission of the Heinreich-Heine-Universität Düsseldorf. We wish to thank Mrs S Küsters for technical assistance and Dr G Kappert for lactate and creatinine measurements.

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  1. Institut für Herz-und Kreislaufphysiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    Z Ding, C Fach, A Sasse, A Gödecke & J Schrader

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  1. Z Ding
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  2. C Fach
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Ding, Z., Fach, C., Sasse, A. et al. A minimally invasive approach for efficient gene delivery to rodent hearts. Gene Ther 11, 260–265 (2004). https://doi.org/10.1038/sj.gt.3302167

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