ABCA4相关Stargardt病基因治疗的研究进展

Research progress on gene therapy for ABCA4-related stargardt disease

Stargardt病(STGD1,OMIM#248200)是最常见的遗传性黄斑营养不良,是由ABCA4基因突变引起的常染色体隐性遗传病。该病通常在儿童晚期或成年早期发病,导致视力进行性、不可逆地损害。近年研究者在STGD1临床和分子特征以及潜在的病理生理学方面取得的重大进展,促成了许多已完成的、正在进行的和计划中的新疗法的人体临床试验。文章聚焦于STGD1的基因治疗研究进展。STGD1基因治疗的主要障碍是ABCA4基因序列过长以及ABCA4基因在光感受器细胞中的特异性转导效率不高。解决这一问题的关键是研究出具有大运载量和能高效将ABCA4基因转导进光感受器细胞的载体。目前STGD1的基因治疗策略主要包括腺相关病毒(adeno-associated viral,AAV)载体、慢病毒载体、纳米颗粒、光遗传学和反义寡核苷酸等。随着研究的深入,未来有望开发出针对STGD1的有效基因治疗方法,为患者带来新的治疗希望。该综述为临床应用和科学研究提供了宝贵的参考和思路。

Stargardt disease(STGD1,OMIM#248200)is the most common hereditary macular dystrophy,caused by mutations in the ABCA4 gene,and is an autosomal recessive inherited disorder.The disease typically manifests in late childhood or early adulthood,leading to progressive and irreversible visual impairment.Significant advances in understanding the clinical and molecular characteristics,as well as the underlying pathophysiology,have ultimately facilitated numerous human clinical trials of new therapies that have been completed,are ongoing,and are planned.This review focuses on the progress in gene therapy research for STGD1.The primary obstacle in STGD1 gene therapy is the lengthy sequence of the ABCA4 gene and the low efficiency of specific transduction of the ABCA4 gene into photoreceptor cells.The key to addressing this issue is to develop a vector with a large carrying capacity that can efficiently transduce the ABCA4 gene into photoreceptor cells.Current gene therapy strategies for STGD1 mainly include adeno-associated viral(AAV)vectors,lentiviral vectors,nanoparticles,optogenetics,and antisense oligonucleotides(AONs).With the deepening of research,it is hoped that effective gene therapy methods for STGD1 will be developed in the future,bringing new therapeutic hope to patients.This review provides valuable references and ideas for clinical applications and scientific research.