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

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Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein. / Dalsgaard, Trine; Kaadt, Claudia Regina Cecchi; Askou, Anne Louise; Bak, Rasmus O; Andersen, Pernille O; Hougaard, David; Jensen, Thomas G; Dagnæs-Hansen, Frederik; Mikkelsen, Jacob Giehm; Corydon, Thomas J; Aagaard, Lars.

I: Molecular Therapy - Nucleic Acids, Bind 12, 07.09.2018, s. 672-683.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{7831b7bd6bc7482db1a56806c6684f5f,
title = "Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein",
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.",
keywords = "CATHETER DELIVERY, DEPENDENT ADENOVIRAL VECTORS, EXPRESSION IN-VIVO, FACTOR-IX, LDL RECEPTOR, LONG-TERM, NONHUMAN-PRIMATES, PIG-LIVER, PLASMID DNA, TRANSGENE EXPRESSION",
author = "Trine Dalsgaard and Kaadt, {Claudia Regina Cecchi} and Askou, {Anne Louise} and Bak, {Rasmus O} and Andersen, {Pernille O} and David Hougaard and Jensen, {Thomas G} and Frederik Dagn{\ae}s-Hansen and Mikkelsen, {Jacob Giehm} and Corydon, {Thomas J} and Lars Aagaard",
note = "Copyright {\textcopyright} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = sep,
day = "7",
doi = "10.1016/j.omtn.2018.07.005",
language = "English",
volume = "12",
pages = "672--683",
journal = "Molecular Therapy - Nucleic Acids",
issn = "2162-2531",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein

AU - Dalsgaard, Trine

AU - Kaadt, Claudia Regina Cecchi

AU - Askou, Anne Louise

AU - Bak, Rasmus O

AU - Andersen, Pernille O

AU - Hougaard, David

AU - Jensen, Thomas G

AU - Dagnæs-Hansen, Frederik

AU - Mikkelsen, Jacob Giehm

AU - Corydon, Thomas J

AU - Aagaard, Lars

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018/9/7

Y1 - 2018/9/7

N2 - 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.

AB - 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.

KW - CATHETER DELIVERY

KW - DEPENDENT ADENOVIRAL VECTORS

KW - EXPRESSION IN-VIVO

KW - FACTOR-IX

KW - LDL RECEPTOR

KW - LONG-TERM

KW - NONHUMAN-PRIMATES

KW - PIG-LIVER

KW - PLASMID DNA

KW - TRANSGENE EXPRESSION

U2 - 10.1016/j.omtn.2018.07.005

DO - 10.1016/j.omtn.2018.07.005

M3 - Journal article

C2 - 30092403

VL - 12

SP - 672

EP - 683

JO - Molecular Therapy - Nucleic Acids

JF - Molecular Therapy - Nucleic Acids

SN - 2162-2531

ER -