Recent advances in liver-directed gene therapy: implications for the treatment of dyslipidemia

Somatic gene therapy for the treatment of dyslipidemia is an area of active investigation. A substantial body of data indicates that the transfer of various lipid-lowering genes to the liver is an effective method of restoring normal plasma lipids in animal models of dyslipidemia. Most studies have used adenoviral vectors because of their excellent gene-transfer efficiency. However, the first and second-generation adenoviral vectors used in these experiments are highly toxic and are associated with substantial morbidity and mortality. This article reviews current data on the properties of two novel vectors, the adeno-associated virus and the helper-dependent adenovirus that is devoid of all protein-encoding genes. Each type of vector has its advantages and drawbacks. They appear to be the most promising vectors to date for liver-directed gene transfer in the treatment of dyslipidemia.