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基因转基因猪的生成和特征与GGTA1/β4GalNT2/CMAH淘汰和人类CD55/CD47表达为异种输血研究

Bin Fang^1,2,3, Chunting Wang^1,2, Yilin Yuan³

¹Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China.

Scientific reports

|December 2, 2024

概括

在灵长类动物中,表达人类CD47和CD55的转基因猪红细胞 (pRBC) 显示了抗体结合的减少和更长的循环时间. 这一进步为异种输血提供了潜在的可能性,以克服血液短缺.

科学领域:

免疫学免疫学免疫学
异种移植 (Xenotransplantation) 是一种异种移植方法.
生物技术是生物技术.

背景情况:

猪红细胞 (pRBC) 是对输血药物短缺的潜在解决方案.
免疫学排斥是pRBCs临床使用的一个重要障碍.
遗传修饰可以改变PRBC免疫性.

研究的目的:

为了产生表达人类CD47 (hCD47) 和CD55 (hCD55) 的多基因编辑猪.
评估这些修饰后的pRBCs的免疫学兼容性.
在灵长类动物模型中评估修饰的PRBCs体内生存率.

主要方法:

用CRISPR/Cas9基因编辑来创建三重淘汰赛 (TKO) 的猪.
对hCD47和hCD55的转基因被引入到TKO猪中.
在Cynomolgus子中进行了抗体结合测定和体内输血研究.

主要成果:

与野生类型的pRBC相比,TKO/hCD47/hCD55 pRBC显示人类IgG和IgM抗体的结合显著减少.
输血的TKO/hCD47/hCD55pRBC在Cynomolgus子中仍然可以检测到输血后2小时.
在同一个模型中,野生类型的pRBC在20分钟内从循环中清除.

结论:

表达hCD47和hCD55的多基因编辑猪可以产生免疫性降低的prbc.
这些修改后的PRBC在非人类灵长类动物模型中表现出更好的生存率.
这一战略对开发用于异体输血的免疫学上兼容的pRBC具有前景.

关键词:

基因编辑基因编辑转基因猪是转基因的猪.在Xenotransfusion中使用Xenotransfusion.

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相关概念视频

Transgenic Organisms

Transgenic Organisms

In-vitro Mutagenesis

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.