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Dalsgaard T, Cecchi CR, Askou AL, et al. Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein. Mol Ther Nucleic Acids. 2018;12:672-683doi: 10.1016/j.omtn.2018.07.005.
Dalsgaard, T., Cecchi, C. R., Askou, A. L., Bak, R. O., Andersen, P. O., Hougaard, D., Jensen, T. G., Dagnæs-Hansen, F., Mikkelsen, J. G., Corydon, T. J., & Aagaard, L. (2018). Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein. Molecular therapy. Nucleic acids, 12672-683. https://doi.org/10.1016/j.omtn.2018.07.005
Dalsgaard, Trine, et al. "Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein." Molecular therapy. Nucleic acids vol. 12 (2018): 672-683. doi: https://doi.org/10.1016/j.omtn.2018.07.005
Dalsgaard T, Cecchi CR, Askou AL, Bak RO, Andersen PO, Hougaard D, Jensen TG, Dagnæs-Hansen F, Mikkelsen JG, Corydon TJ, Aagaard L. Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein. Mol Ther Nucleic Acids. 2018 Sep 07;12:672-683. doi: 10.1016/j.omtn.2018.07.005. Epub 2018 Aug 06. PMID: 30092403; PMCID: PMC6083003.
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Mol Ther Nucleic Acids. 2018 Sep 07;12:672-683. doi: 10.1016/j.omtn.2018.07.005. Epub 2018 Aug 06.

Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein.

Molecular therapy. Nucleic acids

Trine Dalsgaard, Claudia R Cecchi, Anne Louise Askou, Rasmus O Bak, Pernille O Andersen, David Hougaard, Thomas G Jensen, Frederik Dagnæs-Hansen, Jacob Giehm Mikkelsen, Thomas J Corydon, Lars Aagaard

Affiliations

  1. Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark.
  2. Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark; Aarhus Institute of Advanced Studies (AIAS), Aarhus University, DK-8000 Aarhus C, Denmark.
  3. Statens Serum Institut (SSI), DK-2300 Copenhagen S, Denmark.
  4. Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark; Department of Ophthalmology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
  5. Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark. Electronic address: [email protected].

PMID: 30092403 PMCID: PMC6083003 DOI: 10.1016/j.omtn.2018.07.005

Abstract

Delivery of genes to mouse liver is routinely accomplished by tail-vein injections of viral vectors or naked plasmid DNA. While viral vectors are typically injected in a low-pressure and -volume fashion, uptake of naked plasmid DNA to hepatocytes is facilitated by high pressure and volumes, also known as hydrodynamic delivery. In this study, we compare the efficacy and specificity of delivery of vesicular stomatitis virus G glycoprotein (VSV-G) pseudotyped lentiviral vectors to mouse liver by a number of injection schemes. Exploiting in vivo bioluminescence imaging as a readout after lentiviral gene transfer, we compare delivery by (1) "conventional" tail-vein injections, (2) "primed" injections, (3) "hydrodynamic" injections, or (4) direct "intrahepatic" injections into exposed livers. Reporter gene activity demonstrate potent and targeted delivery to liver by hydrodynamic injections. Enhanced efficacy is confirmed by analysis of liver sections from mice treated with GFP-encoding vectors, demonstrating 10-fold higher transduction rates and gene delivery to ∼80% of hepatocytes after hydrodynamic vector delivery. In summary, lentiviral vector transfer to mouse liver can be strongly augmented by hydrodynamic tail-vein injections, resulting in both reduced off-target delivery and transduction of the majority of hepatocytes. Our findings pave the way for more effective use of lentiviral gene delivery in the mouse.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: gene transfer; hepatocytes; high-pressure tail-vein injection; hydrodynamic delivery; in vivo; lentivirus; liver gene therapy

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