rAAV2-Mediated Restoration of GALC in Neural Stem Cells from Krabbe Patient-Derived iPSCs

Autor: Guoshuai Tian, Chunyu Cao, Shuyue Li, Wei Wang, Ye Zhang, Yafeng Lv
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Pharmaceuticals, Vol 16, Iss 4, p 624 (2023)
Druh dokumentu: article
ISSN: 1424-8247
15937909
DOI: 10.3390/ph16040624
Popis: Krabbe disease is a rare neurodegenerative fatal disease. It is caused by deficiency of the lysosomal enzyme galactocerebrosidase (GALC), which results in progressive accumulation of galactolipid substrates in myelin-forming cells. However, there is still a lack of appropriate neural models and effective approaches for Krabbe disease. We generated induced pluripotent stem cells (iPSCs) from a Krabbe patient previously. Here, Krabbe patient-derived neural stem cells (K-NSCs) were induced from these iPSCs. By using nine kinds of recombinant adeno-associated virus (rAAV) vectors to infect K-NSCs, we found that the rAAV2 vector has high transduction efficiency for K-NSCs. Most importantly, rAAV2-GALC rescued GALC enzymatic activity in K-NSCs. Our findings not only establish a novel patient NSC model for Krabbe disease, but also firstly indicate the potential of rAAV2-mediated gene therapy for this devastating disease.
Databáze: Directory of Open Access Journals
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