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

Hum Gene Ther Methods. 2013 Apr;24(2):59-67. doi: 10.1089/hgtb.2012.243. Epub 2013 Apr 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Dependovirus / classification
  • Dependovirus / genetics
  • Dependovirus / immunology*
  • Genetic Therapy*
  • Genetic Vectors / chemistry
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology*
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Mutation
  • Plasmapheresis
  • Seroepidemiologic Studies
  • Transduction, Genetic


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins