Generation and Characterization of Genetically Modified Pigs with GGTA1/β4GalNT2/CMAH Knockout and Human CD55/CD47 Expression for Xenotransfusion Studies

Overview

Journal Sci Rep

Specialty Science

Date 2024 Dec 2

PMID 39622959

Authors

Bin Fang

Chunting Wang

Yilin Yuan

Xiaorui Liu

Lili Shi

Lin Li

Ying Wang

Yifan Dai

Haiyuan Yang

Affiliations

Soon will be listed here.

Abstract

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.

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