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Liver lobe-specific hydrodynamic gene delivery to baboons: A preclinical trial for hemophilia gene therapy
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2023-05-17 , DOI: 10.1016/j.omtn.2023.05.018 Kenya Kamimura 1, 2 , Tsutomu Kanefuji 1 , Takeshi Suda 3 , Takeshi Yokoo 1 , Guisheng Zhang 4 , Yutaka Aoyagi 1 , Dexi Liu 4
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2023-05-17 , DOI: 10.1016/j.omtn.2023.05.018 Kenya Kamimura 1, 2 , Tsutomu Kanefuji 1 , Takeshi Suda 3 , Takeshi Yokoo 1 , Guisheng Zhang 4 , Yutaka Aoyagi 1 , Dexi Liu 4
Affiliation
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Hydrodynamics-based gene transfer has been successfully employed for in vivo gene delivery to the liver of small animals by tail vein injection and of large animals using a computer-assisted and image-guided protocol. In an effort to develop a hydrodynamic gene delivery procedure clinically applicable for gene therapy, we have evaluated the safety and effectiveness of a lobe-specific hydrodynamic delivery procedure for hepatic gene delivery in baboons. Reporter plasmid was used to assess the gene delivery efficiency of the lobe-specific hydrodynamic gene delivery, and plasmid-carrying human factor IX gene was used to examine the pattern of long-term gene expression. The results demonstrated liver lobe-specific gene delivery, therapeutic levels of human factor IX gene expression lasting for >100 days, and the efficacy of repeated hydrodynamic gene delivery into the same liver lobes. Other than a transient increase in blood concentration of liver enzymes right after the injection, no significant adverse events were observed in animals during the study period. The results obtained from this first non-human primate study support the clinical applicability of the procedure for lobe-specific hydrodynamic gene delivery to liver.
中文翻译：
肝叶特异性流体动力学基因递送给狒狒：血友病基因治疗的临床前试验
基于流体动力学的基因转移已成功用于 通过尾静脉注射将体内基因递送到小动物的肝脏，并使用计算机辅助和图像引导方案将大型动物的体内基因递送到肝脏。为了开发临床上适用于基因治疗的流体动力学基因递送程序，我们评估了叶特异性流体动力学递送程序对狒狒肝脏基因递送的安全性和有效性。报告质粒用于评估叶特异性流体动力学基因递送的基因递送效率，使用质粒携带的人因子 IX 基因检测长期基因表达模式。结果显示了肝叶特异性基因递送、持续 >100 天的人类因子 IX 基因表达的治疗水平，以及重复流体动力学基因递送到同一肝叶的疗效。除了注射后血中肝酶浓度的短暂增加外，在研究期间未在动物中观察到明显的不良事件。从第一项非人灵长类动物研究中获得的结果支持该程序将叶特异性流体动力学基因递送到肝脏的临床适用性。
更新日期：2023-05-17
中文翻译：
肝叶特异性流体动力学基因递送给狒狒：血友病基因治疗的临床前试验
基于流体动力学的基因转移已成功用于 通过尾静脉注射将体内基因递送到小动物的肝脏，并使用计算机辅助和图像引导方案将大型动物的体内基因递送到肝脏。为了开发临床上适用于基因治疗的流体动力学基因递送程序，我们评估了叶特异性流体动力学递送程序对狒狒肝脏基因递送的安全性和有效性。报告质粒用于评估叶特异性流体动力学基因递送的基因递送效率，使用质粒携带的人因子 IX 基因检测长期基因表达模式。结果显示了肝叶特异性基因递送、持续 >100 天的人类因子 IX 基因表达的治疗水平，以及重复流体动力学基因递送到同一肝叶的疗效。除了注射后血中肝酶浓度的短暂增加外，在研究期间未在动物中观察到明显的不良事件。从第一项非人灵长类动物研究中获得的结果支持该程序将叶特异性流体动力学基因递送到肝脏的临床适用性。
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