Hepatic gene therapy: Present and future
Hepatic gene therapy: Present and future
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DOI：
10.1002/hep.1840180536
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发表时间：
1993-11
期刊：
影响因子：
13.5
通讯作者：
F. Ledley
中科院分区：
文献类型：
--
作者：
F. Ledley
1992年，肝脏基因治疗的第一个临床试验开始，将低密度脂蛋白（LDL）受体基因导入家族性高胆固醇血症患者的肝脏（1）。这项临床试验和其他即将进行的临床试验可能会验证一系列用于多种肝脏疾病的体细胞基因治疗的新技术。体细胞基因治疗的原理是，基因可以被引入到体内选定的细胞中，以治疗遗传性或获得性疾病（3-5）。体细胞基因治疗类似于细胞或器官移植，其中生物材料被引入体内用于治疗目的。体细胞基因治疗，如目前所设想的，不涉及修复或替换突变基因，并且明确地不涉及操纵精子和卵子中的遗传物质。肝脏基因治疗可为治疗各种遗传性肝功能障碍提供一种方法，如LDL受体缺乏引起的家族性高胆固醇血症、苯丙氨酸羟化酶缺乏引起的苯丙酮尿症或尿素循环遗传缺陷引起的高氨血症。这种疾病可以通过将正常基因导入肝细胞以提供遗传突变基因的功能来治疗。肝脏基因治疗也可以是治疗获得性或多因素疾病的方法，其中重组基因的表达可以改变病理过程的过程。例如，多因素高胆固醇血症、传染性肝炎甚至肝硬化等疾病可能是未来基因治疗的目标。肝脏也可能是基因治疗的重要靶点，基因治疗使用肝细胞作为生物反应器来分泌
In 1992 the first clinical trial of hepatic gene therapy began with the introduction of a gene for the low-density lipoprotein (LDL) receptor into the liver of a patient with familial hypercholesterolemia (1). This clinical trial, and other clinical trials that are imminent (21, may validate a series of novel technologies for somatic gene therapy of a variety of diseases involving the liver. The principle of somatic gene therapy is that genes can be introduced into selected cells in the body to treat genetic or acquired diseases (3-5). Somatic gene therapy is analogous to cell or organ transplantation where biological materials are introduced into the body for therapeutic purposes. Somatic gene therapy, as presently conceived, does not involve repairing or replacing mutant genes and explicitly does not involve manipulation of the inherited genetic material in the sperm and egg. Hepatic gene therapy may provide an approach to therapy for various inherited disorders of hepatic function such as familial hypercholesterolemia caused by LDL-receptor deficiency, phenylketonuria caused by phenylalanine hydroxylase deficiency or hyperammonemia caused by inherited defects in the urea cycle. Such diseases might be treated by introducing a normal gene into hepatic cells to provide the function of the inherited, mutant gene. Hepatic gene therapy may also be an approach for treating acquired or multifactorial diseases where expression of a recombinant gene may alter the course of a pathological process. For example, diseases such as multifactorial hypercholesterolemia, infectious hepatitis or even cirrhosis may be targets for gene therapy in the future. The liver may also be an important target for gene therapies that use hepatocytes as bioreactors to secrete