ApoE gene therapy to treat hyperlipidemia and atherosclerosis

Curr Opin Mol Ther. 2006 Aug;8(4):275-87.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / metabolism
  • Atherosclerosis / genetics
  • Atherosclerosis / therapy*
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Humans
  • Hyperlipidemias / genetics
  • Hyperlipidemias / therapy*
  • Lipid Metabolism


  • Apolipoproteins E