肝脏靶向性基因治疗的研究进展  

Research Progress in Liver-Targeted Gene Therapy

作　　者：刘国庆 时斯婧 杨钧婷 陶怡君 宋国华 王宇辉 LIU Guoqing;SHI Sijing;YANG Junting;TAO Yijun;SONG Guohua;WANG Yuhui(Beijing Genecradle Therapeutics Inc,Ltd.,Beijing 100004,China;Institute of Cardiovascular Science,School of Basic Medicine,Key Laboratory of Vascular Homeostasis and Remodeling,Health Science Center,Peking University,Beijing 100039,China;Laboratory Animal Center,Shanxi Medical University,Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model,Shanxi Taiyuan 030001,China)

机构地区：[1]北京锦篮基因科技有限公司,北京100004 [2]北京大学心血管研究所,北京大学医学部基础医学院,血管稳态与重构全国重点实验室,北京100039 [3]山西医科大学实验动物中心,实验动物与人类疾病动物模型山西省重点实验室,山西太原030001

出　　处：《中国医药导刊》2023年第9期881-890,共10页Chinese Journal of Medicinal Guide

摘　　要：基因治疗是一种通过载体系统将目的基因导入机体发挥治疗作用的新型药物。肝脏靶向性基因治疗不仅可以针对肝脏本身疾病发挥作用,还可利用肝脏作为机体的生物反应器,通过表达的基因产物对全身性或其他器官的疾病发挥治疗作用。由于肝脏具有对进入体内物质的代谢和解毒特性,大多数基因载体都会进入肝脏。因此肝脏靶向性是基因治疗领域的一个重要研究方向。早期由于特异性、疗效、毒性和免疫限制,肝脏靶向性基因治疗的实际临床价值受到限制。随着载体技术和监测技术的不断进步,肝脏靶向性基因治疗现已成为治疗各种肝脏和非肝脏相关疾病的一种具有潜力的方法。本研究在梳理肝脏靶向性基因治疗分类、病毒和非病毒载体系统的基础上,概述肝脏靶向性基因治疗技术进展过程和发展现状,探讨肝脏靶向性基因治疗在肝癌、遗传性系统性疾病、遗传性代谢性肝病、脂代谢紊乱性疾病等方面应用,总结分析当前肝脏靶向性基因治疗存在问题以及潜在解决方案,进一步展望肝脏靶向性基因治疗的未来前景,以期为肝脏靶向性基因治疗的研究和应用提供借鉴和参考,进而促进我国基因治疗的创新发展。Gene therapy is a new drug that introduces target genes into the body through a vector system to exert therapeutic effects.Liver-targeted gene therapy can not only target liver diseases,but also utilize the liver as a bioreactor to treat systemic or other organ diseases through expressed gene products.Due to the liver′s ability tometabolize and detoxify substances entering the body,most of gene vectors enter the liver.Therefore,liver-targeted is an important research direction in the field of gene therapy.In the early stage,due to specificity,efficacy,toxicity,and immune limitation,the practical clinical value of liver-targeted gene therapy is limited.However,with the continuous progress of vector technology and monitoring technology,liver-targeted gene therapy has become a promising method for treating various liver and non liver related diseases.On the basis of reviewing the classification of liver-targeted gene therapy,viral and non-viral vector systems,this review summarized the progress and current status of liver-targeted gene therapy technology,explored the application of liver-targeted gene therapy in liver cancer,hereditary systemic diseases,hereditary metabolic liver diseases,lipid metabolism disorders,and other aspects,and also summarized and analyzed the current problems and potential solutions of liver-targeted gene therapy,and further looked forword to the future prospects of liver-targeted gene therapy,in order to provide insights for the research and application of liver-targeted gene therapy,and thereby promote the development of gene therapy.

关 键 词：基因治疗 肝脏靶向性 病毒载体 非病毒载体 

分 类 号：R575.1[医药卫生—消化系统] R735.7[医药卫生—内科学] Q789[医药卫生—临床医学]