Familial Hypercholesterolemia: Gene Therapy


Familial hypercholesterolemia is a monogenic disease characterized by high levels of plasma cholesterol and premature cardiovascular disease. In its homozygous form, conventional pharmacological therapy is not effective and gene therapy could become a viable treatment.

Keywords: familial hypercholesterolemia; gene therapy; LDL receptor; VLDL receptor; adenoviral vector; adeno‐associated vector; cardiovascular disorders; LDL cholesterol


Chen SJ, Rader DJ, Tazelaar J, et al. (2000) Prolonged correction of hyperlipidemia in mice with familial hypercholesterolemia using an adeno‐associated viral vector expressing very‐low‐density lipoprotein receptor. Molecular Therapy 2: 256–261.

Chowdhury JR, Grossman M, Gupta S, et al. (1991) Long‐term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR‐deficient rabbits. Science 254: 1802–1805.

Grossman M, Rader DJ, Muller DWM, et al. (1995) A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia. Nature Medicine 1: 1148–1154.

Ishibashi S, Brown M, Goldstein J, et al. (1993) Hypercholesterolaemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus‐mediated gene delivery. Journal of Clinical Investigation 92: 883–893.

Kobayashi K, Oka K, Forte T, et al. (1996) Reversal of hypercholesterolemia in low density lipoprotein receptor knockout mice by adenovirus‐mediated gene transfer of the very low density lipoprotein receptor. Journal of Biological Chemistry 271: 6852–6860.

Kozarsky KF, Jooss K, Donahee M, Strauss JF III and Wilson JM (1996) Effective treatment of familial hypercholesterolemia in the mouse model using adenovirus‐mediated transfer of the VLDL receptor gene. Nature Genetics 13: 54–62.

Kozarsky KF, McKinley DR, Austin LL, et al. (1994) In vivo correction of low density lipoprotein receptor deficiency in the Watanabe heritable hyperlipidemic rabbit with recombinant adenoviruses. Journal of Biological Chemistry 269: 13695–13702.

Oka K, Pastore L, Kim IH, et al. (2001) Long‐term stable correction of low‐density lipoprotein receptor‐deficient mice with a helper‐dependent adenoviral vector expressing the very low‐density lipoprotein receptor. Circulation 103: 1274–1281.

Further Reading

Goldstein JL, Hobbs HH and Brown MS (2001) Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, vol. 2, pp. 2863–2913. New York: McGraw‐Hill

Kay MA, Glorioso JC and Naldini L (2001) Viral vectors for gene therapy: the art of turning infectious agent into vehicles of therapeutics. Nature Medicine 7: 33–40.

Mulligan RC (1993) The basic science of gene therapy. Science 260: 926–931.

Web Links

Low density lipoprotein receptor (familial hypercholesterolemia) (LDLR); Locus ID: 3949. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3949

Very low density lipoprotein receptor (VLDLR); Locus ID: 7436. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7436

Low density lipoprotein receptor (familial hypercholesterolemia) (LDLR); MIM number: 606945. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?606945

Very low density lipoprotein receptor (VLDLR); MIM number: 192977. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?192977

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How to Cite close
Cuchel, Marina, and Rader, Daniel J(Jan 2006) Familial Hypercholesterolemia: Gene Therapy. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005751]