Fang Bin, Wang Chunting, Yuan Yilin, Liu Xiaorui, Shi Lili, Li Lin, Wang Ying, Dai Yifan, Yang Haiyuan
Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China.
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China.
Sci Rep. 2024 Dec 2;14(1):29870. doi: 10.1038/s41598-024-81730-2.
Pig red blood cells (pRBCs) represent a promising alternative to address the shortage in transfusion medicine. Nonetheless, a major obstacle to their clinical implementation is immunological rejection. In this study, we generated transgenic pigs expressing human CD47 (hCD47) and CD55 (hCD55) in α1,3-galactosyltransferase KO/β-1,4-N-acetyl-galactosaminyl transferase 2 KO/cytidine monophosphate-N-acetylneuraminic acid hydroxylase KO (TKO) pigs using CRISPR/Cas9 technology. Compared to wild-type pRBCs, TKO/hCD47/hCD55 pRBCs exhibit significantly reduced human IgG/IgM antibody binding. Moreover, when transfused into Cynomolgus monkeys, TKO/hCD47/hCD55 pRBCs remained detectable for 2 h post-transfusion, whereas wild-type pRBCs were eliminated within 20 min. This study demonstrates the potential of multi-gene edited pigs to provide immunologically compatible pRBCs.
猪红细胞（pRBCs）是解决输血医学短缺问题的一种有前景的替代方案。然而，其临床应用的一个主要障碍是免疫排斥。在本研究中，我们使用CRISPR/Cas9技术，在α1,3-半乳糖基转移酶敲除/β-1,4-N-乙酰半乳糖胺基转移酶2敲除/胞苷单磷酸-N-乙酰神经氨酸羟化酶敲除（TKO）猪中生成了表达人CD47（hCD47）和CD55（hCD55）的转基因猪。与野生型pRBCs相比，TKO/hCD47/hCD55 pRBCs与人IgG/IgM抗体的结合显著减少。此外，当输注到食蟹猴体内时，TKO/hCD47/hCD55 pRBCs在输血后2小时仍可检测到，而野生型pRBCs在20分钟内就被清除。本研究证明了多基因编辑猪提供免疫相容性pRBCs的潜力。
