Cell, Tissue and Gene Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Adv Exp Med Biol. 2023;1429:127-155. doi: 10.1007/978-3-031-33325-5_8.
Genome editing has multiple applications in the biomedical field. They can be used to modify genomes at specific locations, being able to either delete, reduce, or even enhance gene transcription and protein expression. Here, we summarize applications of genome editing used in the field of lysosomal disorders. We focus on the development of cell lines for study of disease pathogenesis, drug discovery, and pathogenicity of specific variants. Furthermore, we highlight the main studies that use gene editing as a gene therapy platform for these disorders, both in preclinical and clinical studies. We conclude that gene editing has been able to change quickly the scenario of these disorders, allowing the development of new therapies and improving the knowledge on disease pathogenesis. Should they confirm their hype, the first gene editing-based products for lysosomal disorders could be available in the next years.
基因组编辑在生物医学领域有多种应用。它可以用于在特定位置修饰基因组，能够删除、减少甚至增强基因转录和蛋白质表达。在这里，我们总结了基因组编辑在溶酶体疾病领域的应用。我们专注于开发用于研究疾病发病机制、药物发现和特定变体致病性的细胞系。此外，我们还重点介绍了主要的研究，这些研究将基因编辑作为这些疾病的基因治疗平台，包括临床前和临床研究。我们得出的结论是，基因编辑已经能够迅速改变这些疾病的局面，为新疗法的开发提供了可能，并加深了对疾病发病机制的认识。如果它们能像预期的那样发挥作用，那么基于基因编辑的溶酶体疾病的首款产品可能会在未来几年面世。
