title: AAV-mediated gene therapy for liver diseases: the prime candidate for clinical application?
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Erasmus MC-University Medical Center, Department of Surgery and Laboratory of Experimental Transplantation and Intestinal Surgery, Rotterdam, The Netherlands.
authors.forename: Luc J W
authors.initials: LJ
authors.lastname: van der Laan
authors.forename: Yigang
authors.initials: Y
authors.lastname: Wang
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Qiuwei
authors.initials: Q
authors.lastname: Pan
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics* / Q000276:immunology; D018014:Gene Transfer Techniques / Q000009:adverse effects; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome