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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.

SUBMITTER: Louis Jeune V

PROVIDER: S-EPMC3732124 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy.

Louis Jeune Vedell V Joergensen Jakob A JA Hajjar Roger J RJ Weber Thomas T

Human gene therapy methods 20130403 2

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-existi ...[more]

PMID: 23442094

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