The present invention relates to polyclonal antibodies directed against at least one non-human biological pathogen, or against at least one molecule derived from said pathogen, towards a human or a non-human animal organism, wherein the said polyclonal antibodies are devoid of an antigenic determinant selected in a group comprising (i) N-glycolneuraminic acid (Neu5Gc) and/or (ii) a-1,3-galactose, and their use as a medicament.

Provided herein are genetically modified pigs, porcine organs, tissue, and cells having a reduced propensity to cause a rejection response in a human subject following xenotransplantation. In particular, provided herein are genetically modified pigs lacking nonGal xenoantigens, and porcine cells, tissues, and organs obtained from such genetically modified pigs that are suitable for transplantation into a human. Also provided herein are methods of improving a rejection related symptom in a human subject.

The present invention relates to polyclonal antibodies directed against at least one non-human biological pathogen, or against at least one molecule derived from said pathogen, towards a human or a non-human animal organism, wherein the said polyclonal antibodies are devoid of an antigenic determinant selected in a group comprising (i) N-glycolneuraminic acid (Neu5Gc) and/or (ii) a-1,3-galactose, and their use as a medicament.

Provided is an SgRNA combination, comprising an SgRNA specifically targeting the GGTA1 gene, an SgRNA specifically targeting the CMAH gene and an SgRNA specifically targeting the β4GalNT2 gene. Also provided is a CRISPR/Cas9 vector combination, comprising a GGTA1-CRISPR/Cas9 vector, a CMAH-CRISPR/Cas9 vector and a β4GalNT2-CRISPR/Cas9 vector. Also provided is an applicaton of the CRISPR/Cas9 vector combination in knocking out the GGTA1 gene, the CMAH gene and the β4GalNT2 gene. The knockout rates of the three genes with the specifically targeted SgRNA sequences are respectively 56%, 63%, and 41%. A three genes knockoutpig can be obtained, wherein the three genes related to immune rejectionare knocked out, and heart valves of said pig can be acquired.

The present invention relates to a transgenic cloned pig for xenotransplantation in which porcine endogenous retrovirus (RUN) EnvC is negative, α1,3-galactosyltransferase (GGTA1), CMP-N-acetylneuraminic acid hydroxylase (CMAH), isoglobotrihexosylceramide synthase (iGb3s), and beta-I,4-N-acetyl-galactosaminyl transferase2 (β4GalNT2) are knocked out, and human CD46 and thrombomodulin (TBM) genes are expressed, and to a method of preparing the transgenic cloned pig. The transgenic cloned pig according to the present invention may overcome hyperacute and antigen-antibody mediated immune rejection reaction, immune rejection reaction due to blood coagulation, and immune rejection reaction due to complement activity, without causing transfer of porcine endogenous retrovirus that occurs in xenotransplantation. Therefore, the transgenic cloned pig according to the present invention may be usefully utilized as a donor animal for xenotransplantation of organs and cells.

A blood product may be derived from a gene knockout pig and used in, e.g., medical applications. The binding of the blood product to immunoglobulin in human serum is reduced, and the blood product can have an effect on overcoming hyperacute immune rejection. The blood product may be derived from a gene knockout pig, wherein a GGTA1 gene, a CMAH gene, and/or a β4GalNT2 gene of the gene knockout pig are knocked out, wherein one or more nucleotides in the β4GalNT2 gene encoding one or more amino acids in exon 8 are deleted such that the β4GalNT2 gene is knocked out.

Provided is an SgRNA combination, comprising an SgRNA specifically targeting the GGTA1 gene, an SgRNA specifically targeting the CMAH gene and an SgRNA specifically targeting the 4GalNT2 gene. Also provided is a CRISPR/Cas9 vector combination, comprising a GGTA1-CRISPR/Cas9 vector, a CMAH-CRISPR/Cas9 vector and a 4GalNT2-CRISPR/Cas9 vector. Also provided is an applicaton of the CRISPR/Cas9 vector combination in knocking out the GGTA1 gene, the CMAH gene and the 4GalNT2 gene. The knockout rates of the three genes with the specifically targeted SgRNA sequences are respectively 56%, 63%, and 41%. A three genes knockoutpig can be obtained, wherein the three genes related to immune rejectionare knocked out, and heart valves of said pig can be acquired.

Provided herein are genetically modified pigs, porcine organs, tissue, and cells having a reduced propensity to cause a rejection response in a human subject following xenotransplantation. In particular, provided herein are genetically modified pigs lacking nonGal xenoantigens, and porcine cells, tissues, and organs obtained from such genetically modified pigs that are suitable for transplantation into a human. Also provided herein are methods of improving a rejection related symptom in a human subject.