Green Pharmaceutical Technology Key Laboratory of Luzhou, School of Pharmacy, Southwest Medical University, Luzhou, China.
Clinical Laboratory, First Affiliated Hospital of Yangtze University, Jingzhou, China.
Microb Biotechnol. 2023 Dec;16(12):2278-2291. doi: 10.1111/1751-7915.14358. Epub 2023 Oct 24.
Vaccines and cell therapeutics based on genetic code expansion are emerging. A crucial step in these therapeutic technologies is the oral administration of non-canonical amino acids (ncAAs) to control pathogen growth and therapeutic protein levels in vivo. Investigating the toxicity effects of ncAAs can help identify more suitable candidates for developing genetic code expansion-based vaccines and cell therapeutics. In this study, we determined the effects of three ncAAs, namely, 4-acetyl-phenylalanine (pAcF), 4-iodo-phenylalanine (pIoF), and 4-methoxy-phenylalanine (pMeoF), commonly used in genetic code expansion-based vaccines and cell therapeutics, on the main organs, serum biochemical parameters, and gut microbiota in mice. We observed that pIoF and pMeoF significantly altered serum biochemical parameters to some extent. Moreover, the alterations in the mouse gut microbial composition were considerably greater after the oral administration of pIoF and pMeoF than after that of pAcF, compared with that in the control mice. These findings suggest that pAcF is more suitable than pIoF and pMeoF for application in genetic code expansion-based vaccines and cell therapeutics as it disturbs the physiological and gut microecological balance in mice to a lesser extent.
基于遗传密码扩展的疫苗和细胞疗法正在兴起。这些治疗技术的关键步骤之一是口服非天然氨基酸（ncAAs），以控制体内病原体的生长和治疗性蛋白水平。研究 ncAAs 的毒性作用有助于鉴定更适合开发基于遗传密码扩展的疫苗和细胞疗法的候选物。在本研究中，我们确定了三种常用于基于遗传密码扩展的疫苗和细胞疗法的 ncAAs（即 4-乙酰苯丙氨酸（pAcF）、4-碘苯丙氨酸（pIoF）和 4-甲氧基苯丙氨酸（pMeoF））对小鼠主要器官、血清生化参数和肠道微生物群的影响。我们观察到 pIoF 和 pMeoF 在某种程度上显著改变了血清生化参数。此外，与 pAcF 相比，pIoF 和 pMeoF 口服后小鼠肠道微生物组成的改变要大得多，与对照组相比。这些发现表明，pAcF 比 pIoF 和 pMeoF 更适合用于基于遗传密码扩展的疫苗和细胞疗法，因为它对小鼠的生理和肠道微生态平衡的干扰较小。
