遗传性视网膜疾病腺相关病毒载体基因治疗新进展

腺相关病毒载体(AAV)是目前最重要的病毒工具,已在基因治疗领域得到广泛应用;因其具有体积小、无包膜、无致病性等特点,故而是治疗遗传性视网膜疾病的主要手段之一。目前针对原癌基因酪氨酸激酶基因治疗视网膜色素变性、ND4基因治疗Leber遗传性视神经病变以及Rab伴随蛋白-1基因治疗无脉络膜症的临床试验均发现约一半的患者视力改善。针对AAV基因治疗Leber先天性黑矇、X连锁视网膜劈裂症、全色盲以及老年性黄斑变性的临床试验也正在开展。而关于Stargardt病、Usher综合征、真性小眼球的AAV基因治疗尚在动物实验或理论阶段。目前AAV基因治疗主要用于隐性遗传性视网膜疾病,对于显性遗传性视网膜疾病需采用成簇规律间隔的短回文重复序列及其相关蛋白9技术等来干预。对于遗传性视网膜疾病的治疗,这将是一个重要且复杂的系统性工程,需投入更多人力物力共同参与和研究,期待在不久的将来能有大的突破。

New advances in gene therapy with adenoviral vectors for inherited retinal diseases

Adeno-associated viral vector(AAV)is the most important viral tool and has been widely used in gene therapy.Because of its small size,non-enveloped,non-pathogenic and other characteristics,so it is one of the main means to treat hereditary retinal diseases.Aiming at MERTK for retinitis pigmentosa,ND4 for Leber hereditary optic neuropathy or RPE1 for choroideremia,AAV gene therapy improved half patients'visual acuity in clinic tests.Besides,there are some clinic tests in progress for Leber’s congenital amaurosis,X-linked retinoschisis,Achromatopsia,age-related macular degeneration.But more researches need to be found before clinic test for Stargardt disease,Usher syndrome and nanophthalmos.At present,AAV gene therapy is mainly used for recessive hereditary retinal diseases,and technology is needed to intervene for dominant retinal diseases.For the treatment of hereditary retinal diseases,this will be an important and complex systematic project,which requires more human and material resources to participate in and study together,and we expect to have a great breakthrough in the near future.