title: Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma.
abstract: Sarcomas include some of the most aggressive tumors and typically respond poorly to chemotherapy. In recent years, specific gene fusion/mutations and gene over-expression/activation have been shown to drive sarcoma pathogenesis and development. These emerging genomic alterations may provide targets for novel therapeutic strategies and have the potential to transform sarcoma patient care. The RNA-guided nuclease CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein-9 nuclease) is a convenient and versatile platform for site-specific genome editing and epigenome targeted modulation. Given that sarcoma is believed to develop as a result of genetic alterations in mesenchymal progenitor/stem cells, CRISPR-Cas9 genome editing technologies hold extensive application potentials in sarcoma models and therapies. We review the development and mechanisms of the CRISPR-Cas9 system in genome editing and introduce its application in sarcoma research and potential therapy in clinic. Additionally, we propose future directions and discuss the challenges faced with these applications, providing concise and enlightening information for readers interested in this area.
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA 02114, United States; Department of Orthopaedic, the 2nd Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410011, China.
authors.forename: Tang
authors.initials: T
authors.lastname: Liu
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA 02114, United States.
authors.forename: Jacson K
authors.initials: JK
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic, the 2nd Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410011, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA 02114, United States.
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA 02114, United States.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA 02114, United States. Electronic address: zduan@mgh.harvard.edu.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D064130:CRISPR-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D064113:CRISPR-Cas Systems; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting / Q000379:methods*; D056726:Genetic Association Studies; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009154:Mutation; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D064130:CRISPR-Associated Proteins
keywords: CRISPR-Cas9; Cancer modeling; Gene therapy; Sarcoma