Atherosclerosis remains the leading cause of death in industrialized societies.
Apolipoprotein E (ApoE) is an attractive candidate to treat hypercholesterolemia and
coronary heart disease, as it is a circulating protein with pleiotropic atheroprotective actions.
Here, we describe several "gene addition" approaches and on-going developments to
achieve efficient delivery and long-term expression. The use of recombinant viruses is
discussed, including adeno-associated viral vectors (AAV) where technological advances
now allow the cross-packaging of different AAV serotypes. Nonviral delivery systems are
also described, including plasmids and cell-based therapy. Finally, a radical, alternative
technology to gene addition, which has the potential for permanent cure in many genetic
diseases, is reviewed: "targeted gene repair", which aims to correct underlying point
mutations in-situ. Synthetic oligonucleotides are designed to bind specifically to defective
DNA, enabling the cell's own mismatch machinery to recognize and repair the faulty DNA.
Although such gene editing technology has great potential it remains inconsistent and difficult to reproduce
