The application provides methods of improving a rejection related symptom, reducing premature separation and methods of producing a compound of interest with an altered epitope profile are provided. Knockout pigs with a disrupted gene or genes, and porcine organs, tissues, and cells therefrom are provided.

A biological system for generating and preserving a repository of personalized, humanized transplantable cells, tissues, and organs for transplantation, wherein the biological system is biologically and metabolically active (living), the biological system comprising genetically reprogrammed proteins, cells, tissues, and/or organs in a non-human animal donor for transplantation into a human recipient, wherein the non-human animal donor is a genetically reprogrammed porcine donor for xenotransplantation of cells, tissue, and/or an organ isolated from the genetically reprogrammed porcine donor.

The invention provides methods and compositions for perturbing gene expression in hematopoietic cell lineages in vivo.

Provided are cells, tissues, organs, and/or animals having one or more modified genes for enhanced xenograft survival and/or tolerance. And methods of producing and using the cells, tissues, organs, and/or animals.

Genetically modified cells, tissues, and organs for treating or preventing diseases are disclosed. Also disclosed are methods of making the genetically modified cells and non-human animals.

A biological system for generating and preserving a repository of personalized, humanized transplantable cells, tissues, and organs for transplantation, wherein the biological system is biologically active and metabolically active, the biological system having genetically reprogrammed cells, tissues, and organs in a non-human animal for transplantation into a human recipient, wherein the non-human animal does not present one or more surface glycan epitopes and specific sequences from the wild-type swine's SLA is replaced with a synthetic nucleotides based on a human captured reference sequence from a human recipient's HLA.

Methods, compositions and non-human animals and parts thereof are for improving germ line transmission of genetic modifications. The methods and compositions are for producing non-human embryos with a disrupted or disruptable fertility gene. The embryos can be used as hosts for the development of donor pluripotent cells, including genetically modified donor pluripotent cells, into germ cells and gametes. Additional methods and compositions are for producing from such embryos chimeric non-human animals with a disrupted fertility gene and for breeding the chimeric non-human animals with cognate non-human animals that comprise a fertility gene that lacks a disruption to produce non-human animals having substantially all gametes and/or germ cells derived from the donor pluripotent cells. Non-human gametes, germ cells, embryos and animals can be used in the subject methods.

It is revealed that an organ such as pancreas can be regenerated by utilizing a fact that the deficiency of an organ is complemented by injecting an induced pluripotent stem cell (iPS cell) into a developed blastocyst in a blastocyst complementation method. Thus, the present invention has solved the above-described object. This provides a method for producing a target organ, using an iPS cell, in a living body of a non-human mammal having an abnormality associated with a lack of development of the target organ in a development stage, the target organ produced being derived from a different individual mammal that is an individual different from the non-human mammal.

The present invention provides means for producing an organoid close to an organ in a living body and capable of secretion of a plasma protein and immune response. A matrix composition of the present invention provided as such means includes: (1) a first matrix containing one or more cells selected from the group consisting of vascular cells, nerve cells, and blood cells; and (2) a second matrix containing to cells constituting an organ and/or an organoid, in which the first matrix envelops the second matrix, and the first matrix has at least one opening.

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.