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Open AccessArticle

In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice

1
Department of Pulmonary Medicine, University Hospital Bern, 3010 Bern, Switzerland
2
Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland
3
Institute of Anatomy, University of Bern, 3010 Bern, Switzerland
4
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
5
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
Pharmaceutics 2020, 12(9), 793; https://doi.org/10.3390/pharmaceutics12090793
Received: 22 June 2020 / Revised: 17 August 2020 / Accepted: 18 August 2020 / Published: 21 August 2020
(This article belongs to the Section Gene and Cell Therapy)
Rationale: Mutation in the alpha1 antitrypsin (AAT) gene leads to low circulating levels of AAT, which is associated with several disease processes including pulmonary emphysema. The standard of care relies on substitution with plasma-purified AAT. We studied a novel approach to obtain sustained therapeutic levels of circulating AAT using nonviral in vivo electroporation-mediated gene transfer to the liver. Methods: In vivo intrahepatic electroporation-mediated human AAT gene transfer was performed in C57 Bl/6J mice carrying a genetic deficiency of murine AAT (pallid mice) and suffering from pulmonary emphysema. The animals were evaluated for lung function using flexiVent and detailed stereological assessments. Lung neutrophilic burden was assessed. Results: Pallid mice showed morphologically detectable pulmonary emphysema. Thirty days after in vivo electroporation-mediated gene transfer directly aimed at the liver, circulating human AAT was elevated and lung function was significantly improved compared to non-treated pallid mice. Stereological analysis revealed a reduction in pulmonary emphysema. Conclusion: Our data indicate that in vivo intrahepatic electroporation-mediated gene transfer of AAT is a safe and efficient procedure resulting in reduction of pulmonary emphysema in pallid mice. View Full-Text
Keywords: alpha1 antitrypsin; nonviral gene delivery; electroporation; localized gene delivery; emphysema; liver gene transfer alpha1 antitrypsin; nonviral gene delivery; electroporation; localized gene delivery; emphysema; liver gene transfer
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MDPI and ACS Style

Sutter, M.A.; Cremona, T.P.; Nita, I.; Cavarra, E.; Lungarella, G.; Lewis, E.C.; Schittny, J.C.; Geiser, T.; Gazdhar, A. In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice. Pharmaceutics 2020, 12, 793. https://doi.org/10.3390/pharmaceutics12090793

AMA Style

Sutter MA, Cremona TP, Nita I, Cavarra E, Lungarella G, Lewis EC, Schittny JC, Geiser T, Gazdhar A. In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice. Pharmaceutics. 2020; 12(9):793. https://doi.org/10.3390/pharmaceutics12090793

Chicago/Turabian Style

Sutter, Marco A.; Cremona, Tiziana P.; Nita, Izabela; Cavarra, Eleonora; Lungarella, Giuseppe; Lewis, Eli C.; Schittny, Johannes C.; Geiser, Thomas; Gazdhar, Amiq. 2020. "In Vivo Electroporation-Mediated, Intrahepatic Alpha1 Antitrypsin Gene Transfer Reduces Pulmonary Emphysema in Pallid Mice" Pharmaceutics 12, no. 9: 793. https://doi.org/10.3390/pharmaceutics12090793

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