期刊
GENE THERAPY
卷 26, 期 6, 页码 277-286出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41434-019-0080-9
关键词
-
类别
资金
- Francis S. Collins Scholar Program [1K08CA230179-01]
- DHART-SPORE [IN4689861JHU]
- Children's Tumor Foundation [2016A-05-008, 1R03CA178118-01A1]
- DOD [W81XWH1810236]
- U.S. Department of Defense (DOD) [W81XWH1810236] Funding Source: U.S. Department of Defense (DOD)
Neurofibromatosis type 1, including the highly aggressive malignant peripheral nerve sheath tumors (MPNSTs), is featured by the loss of functional neurofibromin 1 (NF1) protein resulting from genetic alterations. A major function of NF1 is suppressing Ras activities, which is conveyed by an intrinsic GTPase-activating protein-related domain (GRD). In this study, we explored the feasibility of restoring Ras GTPase via exogenous expression of various GRD constructs, via gene delivery using a panel of adeno-associated virus (AAV) vectors in MPNST and human Schwann cells (HSCs). We demonstrated that several AAV serotypes achieved favorable transduction efficacies in those cells and a membrane-targeting GRD fused with an H-Ras C-terminal motif (C10) dramatically inhibited the Ras pathway and MPNST cells in a NF1-specific manner. Our results opened up a venue of gene replacement therapy in NF1-related tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据