通过工程免疫球蛋白G通过胎盘输送治疗性蛋白质:迈向围产期替代疗法的一步
Angelina Mimoun1, Melissa Bou-Jaoudeh1, Sandrine Delignat1
1Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, CNRS, Sorbonne Université, Université Paris Cité, Paris, France.
Journal of thrombosis and haemostasis : JTH
|June 4, 2023
概括
母亲的免疫球蛋白G (IgG) 转移可以保护新生儿. 研究人员证明,工程蛋白质可以穿过小鼠的胎盘,为子宫内疗法提供了潜在的可能性,以纠正遗传疾病或诱导免疫耐受性.
科学领域:
- 免疫学 免疫学 免疫学
- 孕产妇与胎儿的医学
- 蛋白质工程是一种蛋白质工程.
背景情况:
- 母亲免疫球蛋白G (IgG) 为新生儿提供至关重要的幽默免疫力,直到他们自己的免疫系统成熟.
- 母胎界面是治疗胎儿遗传疾病和塑造免疫发育的治疗目标.
- 之前的研究探索了使用这种接口用于酶替代和免疫耐受性诱导.
研究的目的:
- 为了研究孕期小鼠中注射或循环的蛋白质通过胎盘传递的过程.
- 为了确定工程蛋白质是否可以通过胎盘从母亲转移到胎儿.
主要方法:
- 创建了针对人体因子VIII (FVIII) 特定的工程化单价免疫球蛋白G (FabFc) 片段.
- FabFc和FVIII给了患有严重血友病A的怀孕小鼠或为FVIII表达接受基因治疗的小鼠.
- 在母体和胎儿中检测FVIII和FabFc是使用ELISA和免疫组织化学进行的.
主要成果:
- 在FabFc给孕小鼠后,以FcRn依赖的方式实现了FVIII的移植性输送.
- 胎儿的FVIII抗原水平达到正常人血水平的10%左右.
- 优化输送的关键因素包括抗原/FabFc复合物的稳定性,抗原大小和蛋白质补丁的屏蔽.
结论:
- 这项研究表明,使用母胎界面在子宫内提供治疗性蛋白质的可行性.
- 研究结果表明,可能存在新的策略来替代缺陷的胎儿蛋白质或诱导免疫耐受性.
- 这项研究为遗传疾病的产前治疗和免疫调节开辟了道路.
相关概念视频
01:15Transcytosis of IgG
2.8K
Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
2.8K
01:22Development of Immunocompetence
366
The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
366