In vivo high-efficiency transcoronary gene delivery and Cre-LoxP gene switching in the adult mouse heart

Iwatate, Mitsuo and Gu, Yusu and Dieterle, Thomas and Iwanaga, Yoshitaka and Peterson, Kirk L. and Hoshijima, Masahiko and Chien, Kenneth R. and Ross, John jr.. (2003) In vivo high-efficiency transcoronary gene delivery and Cre-LoxP gene switching in the adult mouse heart. Gene Therapy, 10 (21). pp. 1814-1820.

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Official URL: https://edoc.unibas.ch/71063/

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High-efficiency somatic gene transfer in adult mouse heart has not yet been achieved in vivo. Here, we demonstrate high-efficiency in vivo transcoronary gene delivery to the adult murine myocardium using a catheter-based technique with recombinant adenovirus (AdV) and adeno-associated virus (AAV) vectors in normal and genetically engineered mice. The method involves immersion hypothermia followed by transient aortic and pulmonary artery occlusion with proximal intra-aortic segmental injection of cardioplegic solution containing substance P and viral vectors. Gene expression measured using a LacZ marker gene was observed throughout both ventricles. The expression efficiency of a cytoplasmic LacZ marker gene in the left ventricular myocardium was 56.4+/-14.5% (mean+/-s.d.) at 4 days with an AdV vector, and with an AAV vector it was 81.0+/-5.9% at 4 weeks. Following AAV gene transfer, no gene expression was found in kidney, brain, lung, and spleen, but there was slight expression in liver. In addition, we demonstrate temporally controlled genetic manipulation in the heart with an efficiency of 54.6+/-5.2%, by transferring an AdV vector carrying Cre recombinase in ROSA26 flox-LacZ reporter mice. Procedure-related mortality was 16% for AdV and zero for AAV transfer. Thus, this method provides efficient, relatively homogeneous gene expression in both ventricles of the adult mouse heart, and offers a novel approach for conditional gene rescue or ablation in genetically engineered mouse models.
Faculties and Departments:03 Faculty of Medicine
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Kardiologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Kardiologie
UniBasel Contributors:Dieterle, Thomas
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Jul 2020 12:31
Deposited On:06 Jul 2020 12:31

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