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在基因编码扩展治疗中使用非正规氨基酸:对小鼠肠道微生物群的影响

Manyu Liang¹, Yanhong Yang¹, Jing Zhang¹

¹Green Pharmaceutical Technology Key Laboratory of Luzhou, School of Pharmacy, Southwest Medical University, Luzhou, China.

Microbial biotechnology

|October 24, 2023

概括

4-乙-氨酸 (pAcF) 是一种更安全的非正规氨基酸 (ncAA) 用于遗传密码扩展疗法. 与pIoF和pMeoF相比,它在小鼠中引起的生理和肠道微生物群破坏较少.

科学领域:

生物化学和分子生物学
药理学和毒理学药理学和毒理学
微生物学和免疫学

背景情况:

新兴的疫苗和细胞疗法利用遗传密码扩展.
非正规氨基酸 (ncAAs) 的口服是控制治疗性蛋白质水平和病原体生长的关键.
评估ncAAs的毒性对于开发基于基因编码扩展的安全有效疗法至关重要.

研究的目的:

评估三种常用的ncAAs的毒性:4-乙-氨 (pAcF),4--氨 (pIoF) 和4-甲基-氨 (pMeoF).
为了确定这些ncAAs在口服后对小鼠器官,血清生物化学和肠道微生物群的影响.
为基因编码扩展型疫苗和细胞疗法确定最适合的ncAAs.

主要方法:

对小鼠进行pAcF,pIoF和pMeoF的口服.
对主要器官的影响分析.
对血清生物化学参数的评估.
评估肠道微生物群组成的变化.

主要成果:

pIoF和pMeoF显著改变了小鼠的血清生物化学参数.
与pAcF相比,口服pIoF和pMeoF导致肠道微生物组成的变化更大.
与pIoF和pMeoF相比,pAcF对生理和肠道微生态平衡的干扰最小.

结论:

由于其毒性较低,pAcF更适合用于基因编码扩展型疫苗和细胞疗法.
pIoF和pMeoF具有更大的破坏生理和肠道微生态平衡的潜力.
这些发现指导了为更安全的治疗应用选择ncAAs.

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