In vivo electroporation mediated gene delivery to the beating heart

Gene therapy may represent a promising alternative strategy for cardiac muscle regeneration. In vivo electroporation, a physical method of gene transfer, has recently evolved as an efficient method for gene transfer. In the current study, we investigated the efficiency and safety of a protocol invol...

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Bibliographic Details
Published in:PloS one 2010-12, Vol.5 (12), p.e14467-e14467
Main Authors: Ayuni, Erick L, Gazdhar, Amiq, Giraud, Marie Noelle, Kadner, Alexander, Gugger, Mathias, Cecchini, Marco, Caus, Thierry, Carrel, Thierry P, Schmid, Ralph A, Tevaearai, Hendrik T
Format: Article
Language:English
Subjects:
Animals
Arrhythmia
Biocompatibility
Biotechnology
Calcium-binding protein
Cancer
Cardiac muscle
Cardiovascular disease
Cardiovascular Disorders
Creatine
Creatine kinase
Cytomegalovirus
Deoxyribonucleic acid
DNA
Electric pulses
Electroporation
Gene expression
Gene therapy
Gene transfer
Gene Transfer Techniques
Genes
Genes, Reporter
Genetic Therapy - methods
Heart
Heart - physiology
Heart diseases
Heart Diseases - therapy
Heart surgery
Hemodynamics
Histology
Hospitals
In vivo methods and tests
Male
Mammals
Molecular Biology
Muscles
Myocardial Contraction - physiology
Myocardium - enzymology
Ostomy
Plasmids
Plasmids - metabolism
Rats
Rats, Wistar
Regeneration
Rodents
Thoracic surgery
Toxicity
Troponin
Troponin T
Ventricle
Ventricular Function, Left - physiology
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Summary:Gene therapy may represent a promising alternative strategy for cardiac muscle regeneration. In vivo electroporation, a physical method of gene transfer, has recently evolved as an efficient method for gene transfer. In the current study, we investigated the efficiency and safety of a protocol involving in vivo electroporation for gene transfer to the beating heart. Adult male rats were anesthetised and the heart exposed through a left thoracotomy. Naked plasmid DNA was injected retrograde into the transiently occluded coronary sinus before the electric pulses were applied. Animals were sacrificed at specific time points and gene expression was detected. Results were compared to the group of animals where no electric pulses were applied. No post-procedure arrhythmia was observed. Left ventricular function was temporarily altered only in the group were high pulses were applied; CK-MB (Creatine kinase) and TNT (Troponin T) were also altered only in this group. Histology showed no signs of toxicity. Gene expression was highest at day one. Our results provide evidence that in vivo electroporation with an optimized protocol is a safe and effective tool for nonviral gene delivery to the beating heart. This method may be promising for clinical settings especially for perioperative gene delivery.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0014467