ApoE gene therapy to treat hyperlipidemia and atherosclerosis

JD Harris, Vanessa C Evans, JS Owen

Research output: Contribution to journalArticle (Academic Journal)peer-review

17 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)275-287
JournalCurrent Opinion in Molecular Therapeutics
Volume8
Issue number4
Publication statusPublished - Aug 2006

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