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.

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.

Disclosed are viruses, and vaccines comprised of and made from such viruses, that include a heterologous nucleic acid segment encoding α-1,3-galactosyltransferase (α-1,3-GT) such that the nucleic acid segment expresses α-1,3-GT when the virus infects a host cell. Such viruses produce proteins having α-1,3-galactose. The presence of α-1,3-galactose on proteins of infected cells can powerfully stimulate the immune response of the host against the viral proteins of the virus, thus enhancing the effect of the virus as a vaccine. Also disclosed are vaccines that include and/or are produced by such viruses. Also disclosed are methods of making and using such viruses and vaccines, such as administering to a subject in need thereof a vaccine as disclosed and such as making a vaccine that includes one or more viral proteins expressed by a virus as disclosed.

Disclosed are compositions derived from non-primate mammals having reduced expression of alpha 1,3 gal and their use in food products, food additives, cosmetic products, cosmetic additives, medical products, medical devices and products used in research and production of therapeutics. The compositions and methods disclosed are particularly useful to subjects diagnosed with α-Gal Syndrome (AGS).

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.

The present invention relates to the diagnosis, the prevention and the treatment of demyelinating disorders of the central nervous system (CNS), in particular disorders exhibiting altered levels of antibodies directed against α1-3-galactose, such as multiple sclerosis (MS) and clinically isolated syndrome (CIS). The diagnosis of MS and CIS still suffers from a lack of reliable biomarkers and there is cure for these diseases, except medication acting on the immune component of the overt disease, with the usual side effects of the immunosuppression or anti inflammation intended to relieve the associated symptoms. The inventors showed that there is a significant decrease in the levels of antibodies directed against α1-3-galactose in individuals having a MS or a CIS. In addition, the present invention relates to the prevention and/or the treatment of a demyelinating disorder of the CNS in an individual, comprising a step of administering a compound suitable for generating an immune reaction directed against α1-3-galactose in the said individual. Large cohorts of human individuals having MS or CIS have been studied and compared to matched cohorts on the basis of age and gender.

The present application relates to a bi-functional therapeutic for treating cancer that includes a targeting component which targets a tumor-associated antigen and an enzyme which, when delivered to a tumor by said targeting component, converts the tumor phenotype to that of an incompatible allograft or xenograft. The enzyme is coupled to the targeting component. Also disclosed is a method for treating cancer comprising administering the bi-functional therapeutic.

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.