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Gene delivery to the myocardium by intrapericardial injection

Gene Therapy volume 6, pages 683–688 (1999)Cite this article

Abstract

Several studies have demonstrated the feasibility of gene transfer into the heart muscle. However, all the available data also indicate that the extent of transfection remains limited. As an alternative method to intravascular administration, we have developed a novel strategy which uses the pericardial sac. When a replication-deficient adenovirus containing the cDNA encoding a bacterial β-galactosidase is injected into the pericardial sac of adult Wistar rats the staining is exclusively restricted to the pericardial cell layers. However, injecting a mixture of collagenase and hyaluronidase together with the virus, leads to a large diffusion of the transgene activity, reaching up to 40% of the myo- cardium. Transgene expression is predominant in the left ventricle and the interventricular septum but limited in the right ventricle. In vivo echocardiographic measurements of the left ventricular diameters at end diastolic and end systolic times show no difference between virus- and sham-injected animals, thus indicating a good clinical tolerance to this strategy of virus delivery. The same protocol has been used with the same efficiency in mice, which leads us to propose injection into the pericardial sac as an effective and harmless method for gene transfer into the heart muscle.

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Acknowledgements

We thank the Vector Core of the University Hospital of Nantes supported by the Association Française contre les Myopathies (AFM) for providing the AdCMVlacZ vector.

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Authors and Affiliations

  1. INSERM U153 – Institut de Myologie, Paris, France

    Y Fromes, A Salmon, X Wang, H Collin, A Rouche, K Schwartz & M Y Fiszman

  2. Laboratoire de recherche en imagerie, Faculté de Médecine Necker-Enfants Malades, Université Paris V, Paris, France

    A Hagège

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  1. Y Fromes
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  2. A Salmon
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Fromes, Y., Salmon, A., Wang, X. et al. Gene delivery to the myocardium by intrapericardial injection. Gene Ther 6, 683–688 (1999). https://doi.org/10.1038/sj.gt.3300853

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