Your browser doesn't support javascript.
loading
Precise editing of FGFR3-TACC3 fusion genes with CRISPR-Cas13a in glioblastoma.
Wu, Ye; Jin, Weili; Wang, Qixue; Zhou, Junhu; Wang, Yunfei; Tan, Yanli; Cui, Xiaoteng; Tong, Fei; Yang, Eryan; Wang, Jian; Kang, Chunsheng.
Afiliación
  • Wu Y; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin City, Tianjin 300052, China.
  • Jin W; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin City, Tianjin 300052, China.
  • Wang Q; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin City, Tianjin 300052, China.
  • Zhou J; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin City, Tianjin 300052, China.
  • Wang Y; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin City, Tianjin 300052, China.
  • Tan Y; Department of Pathology, Hebei University School of Basic Medical Sciences, Hebei 071000, China; Department of Pathology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China.
  • Cui X; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin City, Tianjin 300052, China.
  • Tong F; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin City, Tianjin 300052, China.
  • Yang E; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin City, Tianjin 300052, China.
  • Wang J; Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Shandong University, 107 Wenhua Xi Road, Jinan 250012, China; Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway. Electronic address: jian.wang@uib.no.
  • Kang C; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin City, Tianjin 300052, China. Electronic address:
Mol Ther ; 29(11): 3305-3318, 2021 11 03.
Article en En | MEDLINE | ID: mdl-34274537
FGFR3-TACC3 (F3-T3) gene fusions are regarded as a "low-hanging fruit" paradigm for precision therapy in human glioblastoma (GBM). Small molecules designed to target the kinase in FGFR currently serve as one form of potential treatment but cause off-target effects and toxicity. Here, CRISPR-Cas13a, which is known to directly suppress gene expression at the transcriptional level and induce a collateral effect in eukaryotes, was leveraged as a possible precision therapy in cancer cells harboring F3-T3 fusion genes. A library consisting of crRNAs targeting the junction site of F3-T3 was designed, and an in silico simulation scheme was created to select the optimal crRNA candidates. An optimal crRNA, crRNA1, showed efficiency and specificity in inducing the collateral effect in only U87 cells expressing F3-T3 (U87-F3-T3). Expression profiles obtained with microarray analysis were consistent with induction of the collateral effect by the CRISPR-Cas13a system. Tumor cell proliferation and colony formation were decreased in U87-F3-T3 cells expressing the Cas13a-based tool, and tumor growth was suppressed in an orthotopic tumor model in mice. These findings demonstrate that the CRISPR-Cas13a system induces the collateral damage effect in cancer cells and provides a viable strategy for precision tumor therapy based on the customized design of a CRISPR-Cas13a-based tool against F3-T3 fusion genes.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Fusión Oncogénica / Glioblastoma / Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos / Sistemas CRISPR-Cas / Edición Génica / Proteínas Asociadas a Microtúbulos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Fusión Oncogénica / Glioblastoma / Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos / Sistemas CRISPR-Cas / Edición Génica / Proteínas Asociadas a Microtúbulos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos