遗传性眼底病基因和干细胞治疗趋势与面临的挑战和机遇

Progress and opportunities of gene and stem cell therapy on hereditary ocular fundus diseases

遗传性眼底病是造成患者视力不可逆损害的一重要原因，因其预后差、临床缺乏有效干预手段而备受关注。随着大量遗传性眼底病致病基因的发现以及基因编辑技术与干细胞技术的发展，基因与干细胞治疗应运而生，成为治愈这类疾病的新希望。基因治疗更多针对早期遗传性眼底病，以导入野生型基因片段替代突变基因来维持现有的视网膜细胞活力；干细胞治疗则更多地针对晚期遗传性眼底病，以健康的干细胞来置换和填充失去功能的视网膜细胞。虽然基因与干细胞治疗仍面临基因脱靶、分化效率、细胞迁移、长期疗效等诸多问题，但其在临床前期及临床试验中取得的成果不容小觑。随着各种新技术和新材料的出现，势必进一步辅助基因与干细胞治疗策略，为遗传性眼底病的临床治愈带来无限机遇和无限可能。

Hereditary ocular fundus disease is an important cause of irreversible damage to patients＇ visual acuity. It has attracted much attention due to its poor prognosis and lack of effective clinical interventions. With the discovery of a large number of hereditary ocular fundus genes and the development of gene editing technology and stem cell technology, gene and stem cell therapy emerged as the new hope for curing such diseases. Gene therapy is more directed at early hereditary ocular fundus diseases, using wild-type gene fragments to replace mutant genes to maintain existing retinal cell viability. Stem cell therapy is more targeted at advanced hereditary ocular fundus diseases, replacing and filling the disabled retinal cell with healthy stem cells. Although gene and stem cell therapy still face many problems such as gene off-target, differentiation efficiency, cell migration and long-term efficacy, the results obtained in preclinical and clinical trials should not be underestimated. With the emergence of various new technologies and new materials, it is bound to further assist gene and stem cell therapy, bringing unlimited opportunities and possibilities for the clinical cure of hereditary ocular fundus diseases.