Poletto Edina, Silva Andrew Oliveira, Weinlich Ricardo, Martin Priscila Keiko Matsumoto, Torres Davi Coe, Giugliani Roberto, Baldo Guilherme
Departamento de Genética, Universidade Federal do Rio Grande do Sul (UFRGS), Porto alegre, Brazil.
Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
Expert Opin Biol Ther. 2023 Apr;23(4):353-364. doi: 10.1080/14712598.2023.2192348. Epub 2023 Mar 20.
Lysosomal storage disorders (LSD) are a group of monogenic rare diseases caused by pathogenic variants in genes that encode proteins related to lysosomal function. These disorders are good candidates for gene therapy for different reasons: they are monogenic, most of lysosomal proteins are enzymes that can be secreted and cross-correct neighboring cells, and small quantities of these proteins are able to produce clinical benefits in many cases. Ex vivo gene therapy allows for autologous transplant of modified cells from different sources, including stem cells and hematopoietic precursors.
Here, we summarize the main gene therapy and genome editing strategies that are currently being used as ex vivo gene therapy approaches for lysosomal disorders, highlighting important characteristics, such as vectors used, strategies, types of cells that are modified and main results in different disorders.
Clinical trials are already ongoing, and soon approved therapies for LSD based on ex vivo gene therapy approaches should reach the market.
溶酶体贮积症（LSD）是一组单基因罕见病，由编码与溶酶体功能相关蛋白质的基因中的致病变异引起。由于多种原因，这些疾病是基因治疗的理想候选对象：它们是单基因疾病，大多数溶酶体蛋白是能够分泌并对邻近细胞进行交叉校正的酶，并且在许多情况下，少量这些蛋白就能产生临床益处。体外基因治疗允许从不同来源（包括干细胞和造血前体细胞）对修饰后的细胞进行自体移植。
在此，我们总结了目前作为溶酶体疾病体外基因治疗方法使用的主要基因治疗和基因组编辑策略，突出了重要特征，如所用载体、策略、修饰的细胞类型以及在不同疾病中的主要结果。
临床试验已经在进行中，基于体外基因治疗方法的LSD批准疗法很快应会上市。
