腺相关病毒载体介导的眼部基因治疗相关免疫应答的研究进展

Advancements in research on immune responses associated with adeno-associated virus vector-mediated ocular gene therapy

腺相关病毒载体已广泛应用于眼部及全身疾病的基因治疗中,然而,临床试验结果表明基因治疗可能引发与免疫炎性反应相关的严重不良事件,从而影响基因治疗的安全性和有效性。基因治疗后引起的眼内免疫炎性反应被称为基因治疗相关葡萄膜炎,这已成为限制眼部长期和有效基因治疗的主要障碍之一。本文从基因治疗的免疫应答机制、相关葡萄膜炎的眼部表现、免疫炎症影响因素和防治策略4个方面进行综述,旨在为发展更安全、有效的眼部基因治疗提供参考。

Adeno-associated virus(AAV)vectors have been widely employed in gene therapy for ocular and systemic diseases.However,clinical trial outcomes have indicated that gene therapy may trigger severe adverse events associated with immune-inflammatory reactions,thereby impacting the safety and efficacy of gene therapy.The immune-inflammatory reaction induced after gene therapy in the eye is referred to as gene therapy-associated uveitis,which has become a major obstacle limiting the long-term and effective use of ocular gene therapy.This review comprehensively explores four aspects:the immune response mechanisms of gene therapy,ocular manifestations of associated uveitis,factors influencing immune inflammation,and preventive and therapeutic strategies.The aim is to provide insights for the development of safer and more effective ocular gene therapy.