Evading and overcoming AAV neutralization in gene therapy

Joseph Earley; Elena Piletska; Giuseppe Ronzitti; Sergey Piletsky

doi:10.1016/j.tibtech.2022.11.006

Evading and overcoming AAV neutralization in gene therapy

Trends Biotechnol. 2023 Jun;41(6):836-845. doi: 10.1016/j.tibtech.2022.11.006. Epub 2022 Dec 9.

Authors

Joseph Earley¹, Elena Piletska², Giuseppe Ronzitti³, Sergey Piletsky²

Affiliations

¹ School of Chemistry, College of Science and Engineering, University of Leicester, Leicester LE1 7RH, UK. Electronic address: je173@leicester.ac.uk.
² School of Chemistry, College of Science and Engineering, University of Leicester, Leicester LE1 7RH, UK.
³ Genethon, 91000 Evry, France; Université Paris-Saclay, Univ. Evry, Inserm, Genethon, Integrare Research Unit UMR_S951, 91000 Evry, France.

PMID: 36503641
DOI: 10.1016/j.tibtech.2022.11.006

Abstract

Adeno-associated virus (AAV)-derived viral vectors are a promising platform for the delivery of curative, life-changing therapies to a huge number of patients with monogenic disorders. There are currently over 250 clinical trials ongoing worldwide. However, for these therapies to benefit as many patients as possible, techniques must be developed to treat those with pre-existing immunity and to potentially allow re-administration of a dose in the future, should efficacy wane over time. This review discusses the current state and prospects of technologies to evade and overcome these immune responses and allow successful treatment of the greatest number of patients possible.

Keywords: AAV; gene therapy; neutralizing antibodies.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing* / genetics
Antibodies, Neutralizing* / therapeutic use
Genetic Therapy / methods
Genetic Vectors*
Humans

Substances

Antibodies, Neutralizing