Intravenous gene therapy for familial hypercholesterolemia using ligand-facilitated transfer of a liposome:LDL receptor gene complex.

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 Hyperlipidemic Rabbits (WHHL), an animal model of FH. Intravenous treatment dose 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.