Pre-existing Anti-adeno-associated Virus Antibodies As a Challenge in AAV Gene Therapy

Overview

Journal Hum Gene Ther Methods

Publisher Mary Ann Liebert

Specialties Genetics
Pharmacology

Date 2013 Feb 28

PMID 23442094

Citations 171

Authors

Vedell Louis Jeune

Jakob A Joergensen

Roger J Hajjar

Thomas Weber

Affiliations

Soon will be listed here.

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.

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