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Ultrasound-mediated gene delivery specifically targets liver sinusoidal endothelial cells for sustained FVIII expression in hemophilia A mice

Mol Ther. 2024-02; 
Savannah M Lawton, Megan A Manson, Meng-Ni Fan, Ting-Yen Chao, Chun-Yu Chen, Peter Kim, Carley Campbell, Xiaohe Cai, Amber Vander Kooi, Carol H Miao
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摘要

The ability to target the native production site of factor VIII (FVIII)-liver sinusoidal endothelial cells (LSECs)-can improve the outcome of hemophilia A (HA) gene therapy. By testing a matrix of ultrasound-mediated gene delivery (UMGD) parameters for delivering a GFP plasmid into the livers of HA mice, we were able to define specific conditions for targeted gene delivery to different cell types in the liver. Subsequently, two conditions were selected for experiments to treat HA mice via UMGD of an endothelial-specific human FVIII plasmid: low energy (LE; 50 W/cm, 150?μs pulse duration) to predominantly target endothelial cells or high energy (HE; 110 W/cm, 150?μs pulse duration) to predominantly target he... More

關(guān)鍵詞

factor VIII, gene transfer, hemophilia, hepatocytes, liver sinusoidal endothelial cells, microbubbles, non-viral gene delivery, ultrasound, ultrasound-mediated gene delivery
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