Bai, Ren-YuanEsposito, DominicTam, Ada J.McCormick, FrankRiggins, Gregory J.Clapp, D. WadeStaedtke, Verena2020-01-032020-01-032019-06Bai, R. Y., Esposito, D., Tam, A. J., McCormick, F., Riggins, G. J., Wade Clapp, D., & Staedtke, V. (2019). Feasibility of using NF1-GRD and AAV for gene replacement therapy in NF1-associated tumors. Gene therapy, 26(6), 277–286. doi:10.1038/s41434-019-0080-9https://hdl.handle.net/1805/21733Neurofibromatosis 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.en-USPublisher PolicyNF1MPNSTAAVGRDGene ReplacementRasArticle