Cardiac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno-associated virus
Abstract Heart failure (HF) is a major burden worldwide, and new therapies are urgently needed. Gene therapy is a promising new approach to treat myocardial diseases. However, current cardiac gene delivery methods for producing global myocardial effects have been inefficient. The aim of this study w...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-51712-5 |
| _version_ | 1797274898694930432 |
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| author | Jaakko Lampela Juho Pajula Niko Järveläinen Satu Siimes Nihay Laham-Karam Antti Kivelä Isidore Mushimiyimana Jussi Nurro Juha Hartikainen Seppo Ylä-Herttuala |
| author_facet | Jaakko Lampela Juho Pajula Niko Järveläinen Satu Siimes Nihay Laham-Karam Antti Kivelä Isidore Mushimiyimana Jussi Nurro Juha Hartikainen Seppo Ylä-Herttuala |
| author_sort | Jaakko Lampela |
| collection | DOAJ |
| description | Abstract Heart failure (HF) is a major burden worldwide, and new therapies are urgently needed. Gene therapy is a promising new approach to treat myocardial diseases. However, current cardiac gene delivery methods for producing global myocardial effects have been inefficient. The aim of this study was to develop an endovascular, reproducible, and clinically applicable gene transfer method for global left ventricular (LV) transduction. Domestic pigs (n = 52) were used for the experiments. Global LV myocardium coverage was achieved by three retrograde injections into the three main LV vein branches. The distribution outcome was significantly improved by simultaneous transient occlusions of the corresponding coronary arteries and the main anastomotic veins of the retroinjected veins. The achieved cardiac distribution was visualized first by administering Indian Ink solution. Secondly, AdLacZ (2 × 1012vp) and AAV2-GFP (2 × 1013vg) gene transfers were performed to study gene transduction efficacy of the method. By retrograde injections with simultaneous coronary arterial occlusions, both adenovirus (Ad) and adeno-associated virus (AAV) vectors were shown to deliver an efficient transduction of the LV. We conclude that retrograde injections into the three main LV veins is a potential new approach for a global LV gene transfer. |
| first_indexed | 2024-03-07T15:05:42Z |
| format | Article |
| id | doaj.art-e1082cb239494cd496817d852e1222e7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:05:42Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e1082cb239494cd496817d852e1222e72024-03-05T18:56:24ZengNature PortfolioScientific Reports2045-23222024-01-0114111010.1038/s41598-024-51712-5Cardiac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno-associated virusJaakko Lampela0Juho Pajula1Niko Järveläinen2Satu Siimes3Nihay Laham-Karam4Antti Kivelä5Isidore Mushimiyimana6Jussi Nurro7Juha Hartikainen8Seppo Ylä-Herttuala9A.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandHeart Hospital, Tampere University HospitalA.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandHeart Center, Kuopio University HospitalA.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandAbstract Heart failure (HF) is a major burden worldwide, and new therapies are urgently needed. Gene therapy is a promising new approach to treat myocardial diseases. However, current cardiac gene delivery methods for producing global myocardial effects have been inefficient. The aim of this study was to develop an endovascular, reproducible, and clinically applicable gene transfer method for global left ventricular (LV) transduction. Domestic pigs (n = 52) were used for the experiments. Global LV myocardium coverage was achieved by three retrograde injections into the three main LV vein branches. The distribution outcome was significantly improved by simultaneous transient occlusions of the corresponding coronary arteries and the main anastomotic veins of the retroinjected veins. The achieved cardiac distribution was visualized first by administering Indian Ink solution. Secondly, AdLacZ (2 × 1012vp) and AAV2-GFP (2 × 1013vg) gene transfers were performed to study gene transduction efficacy of the method. By retrograde injections with simultaneous coronary arterial occlusions, both adenovirus (Ad) and adeno-associated virus (AAV) vectors were shown to deliver an efficient transduction of the LV. We conclude that retrograde injections into the three main LV veins is a potential new approach for a global LV gene transfer.https://doi.org/10.1038/s41598-024-51712-5 |
| spellingShingle | Jaakko Lampela Juho Pajula Niko Järveläinen Satu Siimes Nihay Laham-Karam Antti Kivelä Isidore Mushimiyimana Jussi Nurro Juha Hartikainen Seppo Ylä-Herttuala Cardiac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno-associated virus Scientific Reports |
| title | Cardiac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno-associated virus |
| title_full | Cardiac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno-associated virus |
| title_fullStr | Cardiac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno-associated virus |
| title_full_unstemmed | Cardiac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno-associated virus |
| title_short | Cardiac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno-associated virus |
| title_sort | cardiac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno associated virus |
| url | https://doi.org/10.1038/s41598-024-51712-5 |
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