Introduction: Diseases of the liver represent a major health problem. Often treatments are ineffective, prompting the need for new therapeutic strategies. From extensive preclinical studies, gene therapy in particular mediated by adeno-associated virus (AAV)-derived vectors, has now emerged as the prime candidate for clinical application. AAV-mediated gene therapy for inherited liver diseases has now become a clinical reality, in particular for the treatment of hemophilia B. Areas covered: This review provides a summary of current literature on AAV-mediated gene therapies for both inherited and acquired liver diseases and outlines different strategies to overcome current clinical limitations. The unique properties of AAV over other viral vectors are highlighted as well as the current challenges which are faced for wide-ranging clinical application. Expert opinion: Despite the extensive positive results from animal models, successful application in clinical settings is hampered by immunological barriers. However, immune suppression and other strategies can be employed to overcome these limitations. Given some of their unique advantages, AAV vectors are currently the most obvious candidate for hepatic gene therapy applications, however, serotype-related issues of immune reactivity still represent a formidable barrier for clinical success.

AAV, Adenovirus, Crigler Najjar syndrome, DNA synthesis, RNA interference, RNAi, adeno-associated virus, adenovirus vector, cyclosporin A, daclizumab, dexamethasone, double stranded DNA, familial hypercholesterolemia, gene expression, gene therapy, gene therapy agent, good manufacturing practice, hemophilia, hemophilia A, hemophilia B, hepatic delivery, hepatic gene therapy, hepatitis B, hepatitis C, human, humoral immunity, immunosuppressive treatment, liver cell carcinoma, liver disease, liver graft rejection, liver transplantation, microRNA, mycophenolic acid 2 morpholinoethyl ester, nonhuman, prednisolone, rapamycin, review, serotypes, serotyping, severe combined immunodeficiency, single stranded DNA, tacrolimus, thymocyte antibody, viral gene delivery system, viral vector, virus capsid,
Expert Opinion on Biological Therapy
Erasmus MC: University Medical Center Rotterdam

van der Laan, L.J.W, Wang, Y, Tilanus, H.W, Janssen, H.L.A, & Pan, Q. (2011). AAV-mediated gene therapy for liver diseases: The prime candidate for clinical application?. Expert Opinion on Biological Therapy (Vol. 11, pp. 315–327). doi:10.1517/14712598.2011.548799