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.
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Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
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