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ApoE gene therapy to treat hyperlipidemia and atherosclerosis

Harris, JD; Evans, V; Owen, JS; (2006) ApoE gene therapy to treat hyperlipidemia and atherosclerosis. CURR OPIN MOL THER , 8 (4) 275 - 287. Green open access

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Abstract

Atherosclerosis is the leading cause of death in industrialized countries and is becoming an increasingly worldwide risk to health. Apolipoprotein E (ApoE) is a blood circulating protein with pleiotropic atheroprotective properties that has emerged as a strong candidate for treating hypercholesterolemia and cardiovascular disease. In this review, we discuss the major developments in both viral and non-viral vectors aimed at achieving efficient delivery and sustained expression of an ApoE transgene. The technological advances in engineering viruses include cross-packaging to generate different serotypes of recombinant adeno-associated virus, and the use of multiple-deleted and helper-dependent recombinant adenovirus vectors to minimize immune responses and to package genomic loci. Non-viral ApoE delivery systems, including plasmids and cell-based therapy are also described in this review. Finally, a radical alternative to gene addition that has the potential for permanent cure in many genetic diseases - 'targeted gene editing' - is reviewed. This technology uses synthetic oligonucleotides to correct underlying point mutations in situ and has been evaluated for repairing dysfunctional APOE genes.

Type: Article
Title: ApoE gene therapy to treat hyperlipidemia and atherosclerosis
Open access status: An open access version is available from UCL Discovery
Keywords: adeno-associated virus, adenovirus, ApoE, cardiovascular disease, gene repair, hypercholesterolemia, lipoprotein, E-DEFICIENT MICE, HUMAN APOLIPOPROTEIN-E, RECOMBINANT ADENOASSOCIATED VIRUS, RNA/DNA OLIGONUCLEOTIDES CHIMERAPLASTS, DIET-INDUCED HYPERCHOLESTEROLEMIA, POLYMERASE(-) ADENOVIRUS VECTOR, TRANSDUCTION IN-VIVO, SKELETAL-MUSCLE, INTRAMUSCULAR INJECTION, VIRAL VECTORS
UCL classification: UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)
URI: http://discovery.ucl.ac.uk/id/eprint/2102
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