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

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(9) MDPI 10.3390/pharmaceutics12090793

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)

UniBE Contributor:

Nita, Izabela Magdalena; Schittny, Johannes; Geiser, Thomas and Gazdhar, Amiq

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1999-4923

Publisher:

MDPI

Language:

English

Submitter:

Heidi Lobsiger

Date Deposited:

01 Sep 2020 14:25

Last Modified:

01 Sep 2020 14:40

Publisher DOI:

10.3390/pharmaceutics12090793

PubMed ID:

32825773

Uncontrolled Keywords:

alpha1 antitrypsin electroporation emphysema liver gene transfer localized gene delivery nonviral gene delivery

BORIS DOI:

10.7892/boris.146135

URI:

https://boris.unibe.ch/id/eprint/146135

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