Feasibility of using NF1-GRD and AAV for gene replacement therapy in NF1-associated tumors.
Gene Ther
; 26(6): 277-286, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-31127187
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Neurofibromatose 1
/
Dependovirus
/
Neurofibromina 1
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos