ApoE gene therapy to treat hyperlipidemia and atherosclerosis.
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.
Harris
Julian D
JD
Royal Free & University College Medical School, The UCL Institute of Hepatology, Hampstead Campus, Upper 3rd Floor, Rowland Hill Street, London NW3 2PF, UK. j.harris@medsch.ucl.ac.uk
Evans
Vanessa
V
Owen
James S
JS
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000628:therapy*; D050356:Lipid Metabolism
D001057:Apolipoproteins E