INTRAVENOUS GENE THERAPY FOR FAMILIAL HYPERCHOLESTEROLEMIA USING LIGAND-FACILITATED TRANSFER OF A LIPOSOME : LDL RECEPTOR GENE COMPLEX

家族性高胆固醇血症是一种常染色体显性遗传病，由低密度脂蛋白受体(LDLR)基因突变引起。虽然降低血浆胆固醇降低了冠状动脉疾病的风险，但FH患者对药物治疗的反应很差。转铁蛋白促进的阳离子脂质体兔LDLR基因复合体静脉转移可减轻FH动物模型渡边遗传兔(WHHL)的高胆固醇血症。静脉治疗确实依赖于降低血浆总胆固醇和低密度脂蛋白水平，这与白细胞中低密度脂蛋白受体mRNA转录水平的增加有关。转铁蛋白促进的阳离子脂质体LDLR基因复合体静脉给药可作为治疗FH的重要辅助疗法。

Familial hypercholesterolemia (FH) is an autosomal dominant disorder because of a mutation in the low-density lipoprotein receptor (LDLR) gene. Although lowering plasma cholesterol decreases the risk of coronary artery disease, FH patients respond poorly to pharmacologic treatment. Transferrin-facilitated intravenous transfer of a cationic liposome rabbit LDLR cDNA complex alleviated hypercholesterolemia in Watanabe Heritable rabbits (WHHL), an animal model of FH. Intravenous treatment does dependently decreased plasma total and LDL cholesterol levels, correlating with an increased level of LDLR mRNA transcripts in leukocytes. Transferrin-facilitated intravenous delivery of cationic liposome LDLR gene complexes could serve as an important adjunct therapy for the treatment of FH.