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增强的细菌癌症治疗提供了c-Mycc的治疗性RNA干扰
Jason S Williams1, Adam T Higgins2, Katie J Stott2
1Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea, SA2 8PP, UK.
Cell & bioscience
|March 24, 2024
概括
工程细菌稳定地表达shRNA用于向癌症治疗,显著减少瘤生长并延长小鼠的存活时间. 这种方法为治疗固体瘤提供了一个有希望的新策略,副作用最小.
科学领域:
- 在瘤学瘤学.
- 微生物学 微生物学
- 基因工程是一种基因工程.
背景情况:
- 细菌癌症疗法有着悠久的历史,最近的进展是使用瘤向细菌提供RNA干扰 (RNAi).
- 目前通过等离子体传递RNAi的一个关键限制是体内不稳定性,阻碍了临床翻译.
- 这项研究旨在开发能够稳定地以染色体表达shRNA的细菌,以获得持续的治疗效果.
研究的目的:
- 为了设计减弱的沙门氏甲型菌,以稳定地表达针对c-Myc基因的shRNA.
- 为了评估这些工程细菌在减少c-Myc表达在结直肠和乳腺癌细胞中的有效性.
- 评估这些细菌在肠直肠和乳腺癌小鼠模型中的体内治疗潜力.
主要方法:
- 修改了减弱的沙门氏菌TyphimuriumSL7207菌株与染色体集成的shRNA表达盒.
- 利用结直肠 (SW480,HCT116) 和乳腺 (MCF7) 癌症细胞系进行基因淘汰的体外验证.
- 在体内疗效研究中使用了免疫能力较强的小鼠模型 (Lgr5creERT2Apcflx/flx和BlgCreBrca2flx/flp53flx/flx)
主要成果:
- 工程 SL7207 菌株有效地感染了癌细胞,并实现了显著的RNA和蛋白质淘汰 (50-95%) 的c-Myc在体外.
- 在小鼠中,单次腹膜内注射工程细菌导致瘤殖民,并显著延长了生存期.
- 在对照动物中没有观察到明显的毒性,这表明了有利的安全性.
结论:
- 瘤热带细菌可以被设计为安全有效的治疗基因淘汰.
- 这项技术有可能通过个性化的有效载荷对初级和二级固体瘤进行有针对性的治疗.
- 需要对热带机制和宿主相互作用进行进一步的研究,以获得临床转化.
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