Gene therapy for metabolic diseases of the liver.
Significant advances have been made in the field of liver-directed gene therapy. Many diseases are potential targets for gene therapy, including diseases that have exclusive liver involvement and those with systemic manifestations as a result of defective protein synthesis from the liver. Examples are Crigler-Najjar syndrome type 1, alpha(1)-antitrypsin deficiency and haemophilia A and B. Strategies for gene delivery include the use of viral and nonviral vectors. In addition to previously developed viral vectors, such as retroviruses, adenoviruses and adeno-associated viruses, new viral vectors such as lentiviruses are being investigated extensively. Nonviral vectors for gene delivery include liposomes and receptor-mediated gene therapy. A strategy to correct gene defects has been developed using chimaeric RNA/DNA oligonucleotides, and methods to inhibit aberrant or deleterious gene expression using ribozymes, antisense oligonucleotides and dominant-negative gene products are being developed. However, more research focusing on more efficient gene expression and safety will be required before gene therapy can be routinely applicable.
Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
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