Gene therapy for viral hepatitis

Abstract

Hepatitis B and C infections are two of the most prevalent viral diseases in the world. Existing therapies against chronic viral hepatitis are far from satisfactory due to low response rates, undesirable side effects and selection of resistant viral strains. Therefore, new therapeutic approaches are urgently needed. This review, after briefly summarising the in vitro and in vivo systems for the study of both diseases and the genetic vehicles commonly used for liver gene transfer, examines the existing status of gene therapy-based antiviral strategies that have been employed to prevent, eliminate or reduce viral infection. In particular, the authors focus on the results obtained in clinical trials and experimental clinically relevant animal models.

An Assessment of the Use of Chimpanzees in Hepatitis C Research Past, Present and Future: 1. Validity of the Chimpanzee Model

“…For example, prior to arguably superfluous experi-ments in chimpanzees, the nucleoside analogue, MK-0608, exhibited efficacy in vitro, and its pharmacokinetics were determined in rats, dogs and rhesus macaques (94). The nucleoside inhibitor, B102, and the Heptazyme HCV-translation inhibitor were similarly tested in rats and monkeys (255,(298)(299)(300). A number of modified murine models have also been developed and have been widely utilised (91), such as the uPA-SCID mouse model, in which human hepatocytes are transplanted into immunodeficient mice, to provide a chimaeric liver that can be infected with HCV (301)(302)(303).…”

Virus-triggered autophagy in viral hepatitis - possible novel strategies for drug development

“…Chronic viral hepatitis infection represents a major public health problem worldwide [1,2]. It can be caused by several viruses, the most widespread being hepatitis B and C viruses (HBV and HCV, respectively) [3].…”

Specific activation of 2'-5'oligoadenylate synthetase gene promoter by hepatitis C virus-core protein: A potential for developing hepatitis C virus targeting gene therapy

“…Currently, there is no vaccine to prevent the infection and no specific antiviral drug directed against the disease. Gene therapy has emerged as a novel approach to combat HCV infection in the last few years [2,3] . However, one of the most important obstacles to overcome is "targeting": the appropriate genes must be delivered to and expressed in HCV infected hepatocytes without harming normal tissues.…”