title: Gene therapy in liver diseases: state-of-the-art and future perspectives.
abstract: 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.
authors: Pulmonary Department-Oncology Unit, G. Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece.
authors: Kalliopi
authors: K
authors: Domvri
authors: Paul
authors: P
authors: Zarogoulidis
authors: Konstantinos
authors: K
authors: Porpodis
authors: Maria
authors: M
authors: Koffa
authors: Maria
authors: M
authors: Lambropoulou
authors: Stylianos
authors: S
authors: Kakolyris
authors: George
authors: G
authors: Kolios
authors: Konstantinos
authors: K
authors: Zarogoulidis
authors: Ekaterini
authors: E
authors: Chatzaki
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016464:Lysosomal Storage Diseases / Q000473:pathology / Q000628:therapy; D009154:Mutation; D050130:Oncolytic Virotherapy; D034622:RNA Interference