EX VIVO GENE THERAPY FOR FAMILIAL HYPERCHOLESTEROLEMIA

家族性高胆固醇血症（FH）是一种低密度遗传性疾病 脂蛋白（LDL）受体表达已成为一个重要的 临床模型的基因疗法的发展，针对 肝脏这种疾病的纯合子患者具有严重的 高胆固醇血症和儿童期死于冠状动脉疾病。的 原位肝移植成功纠正了潜在的 FH中的代谢缺陷证实肝细胞是合适的 体细胞基因转移靶。 这项研究表明，移植有限数量的 逆转录病毒转导的肝细胞无发病率， 持续基因表达持续至少四个月后基因 疗法在低水平的代谢后观察到的可变代谢反应 到目前为止，研究的五名患者的基因重建排除了一种可能性。 无修饰的肝定向基因治疗的广泛应用 持续产生大量的基因转移。

Familial Hypercholesterolemia (FH) is an inherited disease of low density lipoprotein (LDL) receptor expression that has emerged as an important clinical model for the development of gene therapies directed to the liver. Patients who are homozygous for this disease have severe hypercholesterolemia and die of coronary artery disease in childhood. The success of orthotopic liver transplantation in correcting the underlying metablic defect in FH confirms that the hepatocyte is an appropriate target for somatic gene transfer. This study demonstrates the feasiblity of engrafting limited numbers of retrovirus-transduced hepatocytes without morbidity and achieving persistent gene expression lasting at least four months after gene therapy. The variable metabolic responses observed following low level genetic reconstitution in the five patients studied thus far precludes a broader application of liver-directed gene therapy without modifications that consistently produce substantially greater gene transfer.