Method for constructing heterogeneous organ transplantation base donor pigs

Abstract

The invention relates to a method for constructing heterogeneous organ transplantation base donor pigs, and belongs to the field of animal biotechnology. On the basis of fetal fibroblasts, three genes, including GGTA1, CMAH and B4GalNT2, are knocked out by the CRISPR / Cas9 gene editing technology, three humanized modifying genes, including hCD55, hCD59 and hCD46, are inserted at fixed points, and the heterogeneous transplantation base donor pigs modified by CMAHKO / B4GalNT2KO / hCD55 / hCD59 / hCD46 genes is constructed according to a somatic cell nuclear transfer technique. The method solves common problems in heterogeneous organ transplantation, including antigen-antibody immunological rejection reaction and complement regulation, to a certain extent, and lays a foundation for research and development of the specific heterogeneous organ transplantation donor pigs suitable for organs, such as hearts, kidneys and livers as well as tissue such as pancreas islet and skin on the basis of base donor pigs, thereby having high application value and promising application prospect in the construction of the multi-gene modified heterogeneous transplantation donor pigs.

Description

technical field [0001] The invention belongs to the field of animal biotechnology, and in particular relates to a method for constructing a basic donor pig for xenogeneic organ transplantation. Background technique [0002] Organ transplantation is the only way to treat patients with end-stage organ failure, while xenotransplantation is the most effective way to solve the severe shortage of human organ donors. In recent years, with the substantial increase of patients with chronic diseases such as diabetes, chronic kidney disease, cardiovascular disease and hepatitis in my country, the number of patients with end-stage liver, kidney, heart and other organ failure is increasing sharply, and the pressure on organ demand will also increase. getting bigger. According to incomplete statistics, my country currently has about 10,000 cases of clinical organ transplants each year, while there are 1.5 million patients waiting for organ transplants. The ratio of the number of patients ...

AI Technical Summary

Problems solved by technology

[0004] Although pigs have been recognized as a source of human organ transplantation, the three major problems of transplantation pathogenic microorganism infection risk, immunological incompatibility and functional impairment make pigs face serious difficulties and key challenges as xenogeneic organ transplantation. to translate into clinical medicine

To this end, the construction of a basic gene-modified pig for xenotransplantation will open up new avenues for xenotransplantation research and help transplantation achieve phased results, such as knocking out α-1,3-galactosidyl transferase (GGTA1) The gene can avoid hyperacute immune rejection, knocking out the porcine endogenous retrovirus (PERVs) gene can avoid the cross-species infection of the virus, and solve the biosafety problem of xenotransplantation, but the immunology is incompatible after xenotransplantation Sexual and functional impairments need more attention

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