Gene Therapy in Liver Diseases: State-of-the-Art and Future Perspectives
Gene therapy is a fundamentally novel therapeutic approach that involves introducing genetic material into target
cells in order to fight or prevent disease. A number of different strategies of gene therapy are tested at experimental
and clinical levels, including: a) replacing a mutated gene that causes disease with a healthy copy of the gene, b) inactivating
a mutated gene that its improper function causes pathogenesis, c) introducing a new gene coding a therapeutic compound
to fight a disease, d) introducing to the target organ an enzyme converting an inactive pro-drug to its cytotoxic metabolite.
In gene therapy, the transcriptional machinery of the patient is used to produce the active factor that exerts the intended
therapeutic effect, ideally in a permanent, tissue-specific and manageable way. The liver is a major target for gene
therapy, presenting inherited metabolic defects of single-gene etiology, but also severe multifactorial pathologies with
limited therapeutic options such as hepatocellular carcinoma. The initial promising results from gene therapy strategies in
liver diseases were followed by skepticism on the actual clinical value due to specificity, efficacy, toxicity and immune
limitations, but are recently re-evaluated due to progress in vector technology and monitoring techniques. The significant
amount of experimental data along with the available information from clinical trials are systematically reviewed here and
presented per pathological entity. Finally, future perspectives of gene therapy protocols in hepatology are summarized.
Keywords: Hepatocellular, gene therapy, liver, metabolic disorder, vector, hepatocellular, gene therapy, liver, metabolic disorder, vector, immune limitations, hepatocellular carcinoma, pharmacotherapy
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