Adeno-associated virus as a gene therapy vector: strategies to neutralize the neutralizing antibodies

Clin Exp Med. 2019 Aug;19(3):289-298. doi: 10.1007/s10238-019-00557-8. Epub 2019 May 3.

Abstract

Adeno-associated virus (AAV)-derived vectors are currently the most common type of viral vectors used in gene therapy clinical trials. The presence of neutralizing antibodies (NAbs) against wild-type AAVs in the host body is one of the limitations for the successful use of AAV vectors. AAV capsid manipulation, by which recombinant vectors lose their ability to interact with NAbs, can help overcome this obstacle. Various methods can be used for this purpose, including directed evolution as well as conjugation of certain chemical groups to AAV epitopes. The present review concisely explains the use of AAV vectors in the clinic for gene therapy of some diseases, their limitations, and solutions to these limitations.

Keywords: Adeno-associated vectors; Capsid modification; Gene therapy; Neutralizing antibodies.

Publication types

  • Review

MeSH terms

  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Dependovirus / genetics*
  • Dependovirus / immunology
  • Drug Carriers
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Humans

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Drug Carriers