Ocular Inflammation and Treatment Emergent Adverse Events in Retinal Gene Therapy

Viruses are the ideal vehicles to deliver therapeutic genes to target tissues. Viral vectors used for gene therapy differ from their natural parent viruses in that they are nonreplicative, nonpathogenic, and are delivered as a high-titer bolus at an unnatural site.1 However, similarities between the natural virus and viral delivery vector, such as capsid proteins, may result in host immune responses that may limit gene transfer or transgene expression. In addition, the transgene product may also be targeted by the immune system resulting in ocular inflammation and removal of transduced cells. Finally, treatment emergent adverse events (TEAEs) may be associated with technical challenges of delivering viral vectors to the eye. Here, we review host immune responses to viral-mediated gene transfer, the role of ocular immune privilege, and factors that determine immunogenicity of retinal gene therapies. We discuss ocular inflammation and TEAEs from preclinical and clinical studies and explore strategies to mitigate these responses.