High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection
Adeno-associated virus (AAV) is one of the most important gene delivery vehicles for in vivo gene therapy. Intramuscular (i.m.) and intravascular (i.v.) injection are commonly used for AAV gene transfer. Unfortunately, the fate of AAV vectors following administration remains unclear at the histologi...
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doaj-4fb0a205845f4a4dad366edfc05409472020-11-25T03:48:07ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012020-09-0118856868High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic InjectionJunling Zhao0Yongping Yue1Aman Patel2Lakmini Wasala3Jacob F. Karp4Keqing Zhang5Dongsheng Duan6Yi Lai7Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USADepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USADepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA; School of Medicine, Saint Louis University, St. Louis, MO 63104, USADepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USADepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USADepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USADepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA; Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65212, USA; Department of Neurology, School of Medicine, University of Missouri, Columbia, MO 65212, USA; Department of Bioengineering, University of Missouri, Columbia, MO 65212, USA; Corresponding author: Dongsheng Duan, PhD, Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Medical Sciences Building, One Hospital Drive, Columbia, MO 65212, USA.Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA; Corresponding author: Yi Lai, PhD, Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Medical Sciences Building, One Hospital Drive, Columbia, MO 65212, USA.Adeno-associated virus (AAV) is one of the most important gene delivery vehicles for in vivo gene therapy. Intramuscular (i.m.) and intravascular (i.v.) injection are commonly used for AAV gene transfer. Unfortunately, the fate of AAV vectors following administration remains unclear at the histological level. Taking advantage of RNAscope, a recently developed in situ hybridization technique that can reveal high-resolution viral DNA localization information, in this study, we evaluated body-wide distribution of an AAV9 vector in the context of the cell and tissue microenvironments. We observed distinctive kinetics of cell and nuclear entry of the AAV DNA in striated muscle and liver following i.m. and i.v. injection. We also found characteristic distribution patterns of the AAV DNA in various histological structures in internal organs, including gonads and lymph nodes, following i.v. injection. Finally, we showed significantly body-wide spreading of the AAV DNA following i.m. injection. These results add a new dimension to our understanding of AAV transduction biology and provide a basis for assessing the full impact of AAV gene therapy.http://www.sciencedirect.com/science/article/pii/S2329050120301728in situ hybridizationRNAscopeAAVhistologyintramuscularintravenous |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Junling Zhao Yongping Yue Aman Patel Lakmini Wasala Jacob F. Karp Keqing Zhang Dongsheng Duan Yi Lai |
spellingShingle |
Junling Zhao Yongping Yue Aman Patel Lakmini Wasala Jacob F. Karp Keqing Zhang Dongsheng Duan Yi Lai High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection Molecular Therapy: Methods & Clinical Development in situ hybridization RNAscope AAV histology intramuscular intravenous |
author_facet |
Junling Zhao Yongping Yue Aman Patel Lakmini Wasala Jacob F. Karp Keqing Zhang Dongsheng Duan Yi Lai |
author_sort |
Junling Zhao |
title |
High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection |
title_short |
High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection |
title_full |
High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection |
title_fullStr |
High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection |
title_full_unstemmed |
High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection |
title_sort |
high-resolution histological landscape of aav dna distribution in cellular compartments and tissues following local and systemic injection |
publisher |
Elsevier |
series |
Molecular Therapy: Methods & Clinical Development |
issn |
2329-0501 |
publishDate |
2020-09-01 |
description |
Adeno-associated virus (AAV) is one of the most important gene delivery vehicles for in vivo gene therapy. Intramuscular (i.m.) and intravascular (i.v.) injection are commonly used for AAV gene transfer. Unfortunately, the fate of AAV vectors following administration remains unclear at the histological level. Taking advantage of RNAscope, a recently developed in situ hybridization technique that can reveal high-resolution viral DNA localization information, in this study, we evaluated body-wide distribution of an AAV9 vector in the context of the cell and tissue microenvironments. We observed distinctive kinetics of cell and nuclear entry of the AAV DNA in striated muscle and liver following i.m. and i.v. injection. We also found characteristic distribution patterns of the AAV DNA in various histological structures in internal organs, including gonads and lymph nodes, following i.v. injection. Finally, we showed significantly body-wide spreading of the AAV DNA following i.m. injection. These results add a new dimension to our understanding of AAV transduction biology and provide a basis for assessing the full impact of AAV gene therapy. |
topic |
in situ hybridization RNAscope AAV histology intramuscular intravenous |
url |
http://www.sciencedirect.com/science/article/pii/S2329050120301728 |
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