Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein.
Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein.
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DOI：
10.1016/j.omtn.2018.07.005
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发表时间：
2018-09-07
期刊：
影响因子：
--
通讯作者：
Aagaard L
中科院分区：
文献类型：
--
作者：
Dalsgaard T;Cecchi CR;Askou AL;Bak RO;Andersen PO;Hougaard D;Jensen TG;Dagnæs-Hansen F;Mikkelsen JG;Corydon TJ;Aagaard L
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.
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影响因子：
3
作者：
Jakobsen, Jannik Ejnar;Johansen, Marianne G.;Schmidt, Mette;Dagnaes-Hansen, Frederik;Dam, Karen;Gunnarsson, Anders;Liu, Ying;Kragh, Peter M.;Li, Rong;Holm, Ida E.;Callesen, Henrik;Mikkelsen, Jacob Giehm;Nielsen, Anders Lade;Jorgensen, Arne Lund
通讯作者：
Jorgensen, Arne Lund
影响因子：
3.7
作者：
Kamimura K;Kanefuji T;Yokoo T;Abe H;Suda T;Kobayashi Y;Zhang G;Aoyagi Y;Liu D
通讯作者：
Liu D
影响因子：
5.1
作者：
Bursill, C. A.;McNeill, E.;Channon, K. M.
通讯作者：
Channon, K. M.
影响因子：
12.4
作者：
Kamimura, Kenya;Suda, Takeshi;Liu, Dexi
通讯作者：
Liu, Dexi
影响因子：
20.3
作者：
Park, F;Ohashi, K;Kay, MA
通讯作者：
Kay, MA