Author:
Hu Yawei,Zhang Hao,Guo Zengfeng,Zhou Jianhua,Zhang Wang,Gong Ming,Wu Jiawen
Abstract
AbstractImprovements in treatment and chemotherapy have increased the survival rate of osteosarcoma, but overall efficacy remains low, highlighting the need for new gene therapy methods. Clustered regularly interspaced short palindromic repeats–deactivated Cas9 (CRISPR–dCas9) technology offers a promising strategy, but targeting osteosarcoma cells precisely is a challenge. We designed a system to achieve specific expression of CRISPR–dCas9–KRAB in osteosarcoma cells by using the creatine kinase muscle (CKM) promoter to drive dCas9–KRAB and the telomerase reverse transcriptase (TERT) promoter to drive single guide (sg)RNA expression. We inhibited the MDM2 proto-oncogene using this system in vitro, which efficiently inhibited the malignant behavior of osteosarcoma cells and induced apoptosis without affecting normal cells. In vivo experiments demonstrated that this system effectively inhibited the growth of subcutaneously transplanted tumors in nude mice. These findings provide a new method for precise identification and intervention of osteosarcoma with significant implications for the development of gene therapy methods for other cancers. Future research should focus on optimizing this system for clinical translation.
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology,Biochemistry
Reference30 articles.
1. de Azevedo JWV, de Medeiros Fernandes TAA, Fernandes JV Jr, de Azevedo JCV, Lanza DCF, Bezerra CM, Andrade VS, de Araújo JMG, Fernandes JV. Biology and pathogenesis of human osteosarcoma. Oncol Lett. 2020;19(2):1099–116.
2. Arndt CA, Rose PS, Folpe AL, Laack NN. Common musculoskeletal tumors of childhood and adolescence. Mayo Clin Proc. 2012;87(5):475–87.
3. Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33(27):3029–35.
4. Stone JB, DeAngelis LM. Cancer-treatment-induced neurotoxicity—focus on newer treatments. Nat Rev Clin Oncol. 2016;13(2):92–105.
5. Harris MA, Hawkins CJ. Recent and ongoing research into metastatic osteosarcoma treatments. Int J Mol Sci. 2022;23(7):3817.
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