title: Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy.
abstract: Adeno-associated virus (AAV)-based vectors are promising tools for gene therapeutic applications, in part because AAVs are nonpathogenic viruses, and vectors derived from them can drive long-term transgene expression without integration of the vector DNA into the host genome. AAVs are not strongly immunogenic, but they can, nonetheless, give rise to both a cellular and humoral immune response. As a result, a significant fraction of potential patients for AAV-based gene therapy harbors pre-existing antibodies against AAV. Because even very low levels of antibodies can prevent successful transduction, antecedent anti-AAV antibodies pose a serious obstacle to the universal application of AAV gene therapy. In this review, we discuss the current knowledge of the role of anti-AAV antibodies in AAV-based gene therapy with a particular emphasis on approaches to overcome the hurdle that they pose.
authors: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors: Vedell
authors: V
authors: Louis Jeune
authors: Jakob A
authors: JA
authors: Joergensen
authors: Roger J
authors: RJ
authors: Hajjar
authors: Thomas
authors: T
authors: Weber
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D000229:Dependovirus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D009154:Mutation; D010956:Plasmapheresis; D016036:Seroepidemiologic Studies; D014161:Transduction, Genetic
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins