使用5'-Cap1和N1-methylpseudouridine修饰的mRNA进行巨细胞制造和工程
Peixuan Zhang1, Yantai Wang2, Jinfeng Jiang3
1Departments of Obstetrics & Gynecology and Pediatrics, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Center of Growth, Metabolism and Aging, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, China.
Molecular therapy. Methods & clinical development
|September 4, 2024
概括
这项研究介绍了一种巨细胞制造平台 (Mo-Mac),该平台使用修饰的mRNA增强了细胞治疗潜力. 工程巨细胞在肝损伤模型中改善了器官恢复,展示了用于治疗应用的多功能mRNA技术.
科学领域:
- 细胞和分子医学 细胞和分子医学
- 生物技术是生物技术.
- 免疫治疗是一种免疫疗法.
背景情况:
- 基于巨细胞的细胞疗法为癌症治疗和组织修复提供了希望.
- 可复制的制造和工程对于实现巨细胞的治疗潜力至关重要.
- 目前的方法需要优化,以实现大规模,一致的生产.
研究的目的:
- 建立一个强大的巨细胞制造平台 (Mo-Mac).
- 通过使用N1-methylpseudouridine (m1Ψ) 修饰的mRNA技术来增强巨细胞的功能.
- 在临床前模型中证明工程巨细胞的治疗疗效.
主要方法:
- 开发一个符合良好制造实践 (GMP) 的巨细胞制造平台 (Mo-Mac).
- 利用单细胞转录组分析来表征细胞组成并指导质量控制.
- 使用编码CD300LF的m1Ψ修饰的mRNA进行工程化巨细胞,以增强吞能力 (细胞).
- 在对乙氨基诱导的急性肝衰竭的小鼠模型中评估治疗疗效.
主要成果:
- >90%的制造产品由巨细胞组成,其中还存在其他免疫细胞.
- 编码CD300LF的m1Ψ修饰的mRNA在体外显著增加了巨细胞效细胞.
- 在急性肝衰竭的小鼠模型中,CD300LF-mRNA工程巨促进了肝脏器官的恢复.
- 开发了与监管标准一致的流细胞计量策略,用于质量评估.
结论:
- 一个符合GMP的巨细胞制造平台 (Mo-Mac) 已成功建立.
- 巨细胞的功能可以有效地提高使用多功能mRNA工程.
- 工程化巨细胞在治疗急性肝衰竭等疾病方面显示出治疗潜力.
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