腺相关病毒不同递送途径对视网膜基因治疗影响的研究进展

Research progress of effect of different delivery routes of adeno-associated virus on retinal gene therapy

遗传性视网膜病变的治疗有赖于基因的替代或编辑治疗,而腺相关病毒(AAV)载体是应用最广泛的基因转移载体之一。目前将AAV载体介导的目标基因递送到视网膜的方式包括玻璃体腔注射、视网膜下注射、脉络膜上腔注射。玻璃体腔注射AAV载体是目前最常用的递送方式,可有效改善小鼠致盲性视网膜营养不良等眼底病变。而视网膜下注射AAV,可将目的基因靶向递送至局部视网膜,达到更强的转染效率和基因表达效果,但操作技术要求较高。近些年,作为备受瞩目的递送新途径,脉络膜上腔注射AAV载体,可使目的基因在兔和大鼠视网膜上更为广泛的转染。目前AAV载体在视网膜上的转导效率受到递送模式的影响。未来需进一步探索AAV载体的递送模式对转导效率的影响,以期寻找介导基因治疗视网膜疾病的重要递送途径。

The treatment of hereditary retinopathy depends on gene replacement or editing therapy,and adeno-associated virus(AAV)vector is one of the most widely used gene transfer vectors.The delivery methods of AAV vector-mediated target genes to the retina inlucde intravitreal injection,subretinal injection,and suprachorioidal injection.Intravitreal injection of AAV vector is currently the most commonly used delivery route,which can effectively improve the functions of retina disorders such as blinding retinal dystrophy in mice.Subretinal injection of AAV vector can deliver the target gene to the local retina,resulting in stronger efficiency of transfection and gene expressio,however,the high technical operations are required.In recent years,as a new high-profile delivery route suprachorioidal injection of AAV vector can achieve more extensive transfection of target genes in the retina of rabbits and rats.At present,the efficiency of AAV vector transduction in the retina is affected by the delivery mode.In the future,it is necessary to further explore the effect of AAV vector delivery mode on the transduction efficiency in order to find an important delivery route for mediating gene therapy for retinal diseases.