Repository logo

Humoral immune responses to AAV gene therapy in the ocular compartment.

Published version

Change log


Osborne, Andrew 
Yu-Wai-Man, Patrick 
Martin, Keith 


Viral vectors can be utilised to deliver therapeutic genes to diseased cells. Adeno-associated virus (AAV) is a commonly used viral vector that is favoured for its ability to infect a wide range of tissues whilst displaying limited toxicity and immunogenicity. Most humans harbour anti-AAV neutralising antibodies (NAbs) due to subclinical infections by wild-type virus during infancy and these pre-existing NAbs can limit the efficiency of gene transfer depending on the target cell type, route of administration and choice of serotype. Vector administration can also result in de novo NAb synthesis that could limit the opportunity for repeated gene transfer to diseased sites. A number of strategies have been described in preclinical models that could circumvent NAb responses in humans, however, the successful translation of these innovations into the clinical arena has been limited. Here, we provide a comprehensive review of the humoral immune response to AAV gene therapy in the ocular compartment. We cover basic AAV biology and clinical application, the role of pre-existing and induced NAbs, and possible approaches to overcoming antibody responses. We conclude with a framework for a comprehensive strategy for circumventing humoral immune responses to AAV in the future.



AAV, gene therapy, immune response, neutralizing antibodies, ocular, retina, Dependovirus, Genetic Therapy, Genetic Vectors, Humans, Immunity, Humoral

Journal Title

Biol Rev Camb Philos Soc

Conference Name

Journal ISSN


Volume Title



Addenbrookes Charitable Trust (G104080, G109216)
Medical Research Council (MR/R502303/1)
National Eye Research Council (G104080)
Novo Nordisk UK Research Foundation (G103197)