The present invention relates to novel strains of pig that are highly suitable for xenotransplantation. The first novel pig strain lacks functional porcine endogenous retroviruses so is suitable as a donor for tissue and/or cell xenotransplantation into a human recipient. These pigs can also be used as a foundation pig for further manipulation, for example, by gene editing of xenoantigens to produce a second novel strain of pig that is not only free of infectious porcine retroviruses but is also free of the main xenoantigens responsible for hyperacute organ rejection. These pigs can be used for whole organ, tissue and/or cell transplantation into a human recipient. The present invention also relates to methods for selecting pigs that lack infectious porcine endogenous retroviruses, and their use for tissue and/or cell xenotransplantation into humans, and to methods of gene editing of xenoantigens of the selected pigs to further enhance the immunological quality of the donor organs, tissues and/or cells to avoid xenotransplant rejection.

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.

The invention provides for transgenic donor animals (e.g., pigs) whose cells, tissues and organs have a better long-term survival when transplanted into a human patient. The transgenic donor animal carries one or more human transgenes which is expressed only when the endogenous gene of the donor animal is knocked out shortly before a graft is harvested for transplantation. This “genetic switch” allows the donor animal to remain healthy during the majority of its lifetime, while still allowing expression of the human transgene for optimal transplant tolerance in a human recipient. The transgene may encode a cytokine receptor, an adhesion molecule, or a complement regulatory protein.

The invention relates to a shed with a defecation region, a rest region, a feeding region and an activity region. The floor of the defecation region is formed by the upper run of a conveyor belt, through which urine that is produced can pass. A collecting trough for the urine is arranged under the upper run of the conveyor belt, from which collecting trough the urine is guided away and directed into a urine collection container outside the shed. An excrement scraper is disposed proximate the conveyor belt in the region of the rear deflection thereof. The excrement scraper, during the forward movement of the conveyor belt, scrapes the excrement on the conveyor belt off onto a discharge conveyor belt, in such a way that a separation of excrement and urine takes place.

Two long-acting recombinant porcine FSH (follicle-stimulating hormone) fusion proteins, comprising pFSH-Fc-1 and pFSH-Fc-2. α subunit/β subunit is directly or indirectly fused on a Fc fragment by means of a linking component; the β subunit/α subunit is combined with the α subunit/β subunit by means of a Van der Waals force or the linking component. The porcine FSH fusion proteins can be prepared by an eukaryotic expression system based on a gene engineering technology. The two porcine FSH fusion proteins have a good medicinal effect and have a longer half-life period as compared with that of a natural porcine FSH; the two porcine FSH fusion proteins do not generate an undesirable effect on animals and can replace pregnant mare serum gonadotropin (PMSG) to be used in animal breeding production. The two porcine FSH fusion proteins can be used for preparation of medicines in the field of animal breeding.

The present disclosure provides compositions and methods related to the generation and use of transgenic animal models having stem cell reporter systems. In particular, the present disclosure provides a novel transgenic animal model that expresses a nuclear-localized fluorescent reporter in cells endogenously expressing a leucine-rich repeat-containing G-protein coupled receptor (LGR) gene (e.g., LGR5gene). Given the role of LGR genes in stem cell and cancer biology, the transgenic animal models provided herein are useful for a wide range of therapeutic and diagnostic purposes.

This disclosure provides new animal models for studying Usher syndrome and developing new therapy. The technology is implemented in pigs, and other large animals in which the ophthalmic architecture and function more closely resembles architecture and function of the human eye. The animals have a genetic modification in which all or a portion of a human gene known to cause Usher syndrome in human patients replaces the host gene. Animals can be cloned or bred to be homozygous at the targeted locus, whereupon they manifest symptoms and signs of Usher syndrome. Since a substantial portion of the targeted gene has been humanized, the animals can be used to develop and test pharmacological agents such as gene therapy that are sequence dependent.

A method for improving intestinal flora increases the number of beneficial bacteria such as lactic acid bacteria and Bifidobacterium to improve intestinal flora by using an enzyme. The method involves providing a protease, which is a polypeptide having an amino acid sequence shown in SEQ ID NO: 1 that can increase beneficial bacteria such as lactic acid bacteria and Bifidobacterium in intestines to exert an excellent effect of improving intestinal flora.

The present invention relates to an in vitro immune synapse system and a method of in vitro evaluating immune response using the same. The in vitro immune synapse system includes antigen-presenting cells (APCs) and at least one cell type of several specific T cell subtypes isolated from peripheral blood mononuclear cells (PBMCs), all of which is from a same individual of pigs. When a test sample is co-cultured in the in vitro immune synapse system for a given period, it can be determined that the test sample is immunogenic, immunostimulatory or not according to the immunization-related changes of these cells, thereby potentially replacing some kinds of animal experimentation.

The present invention provides certain donor animals, tissues and cells that are particularly useful for xenotransplantation therapies. In particular, the invention includes porcine animals, as well as tissue and cells derived from these, which lack any expression of functional alpha 1,3 galactosyltransferase (aGT) and express one or more additional transgenes which make these animals suitable donors for xenotransplantation of vascularized xenografts and derivatives thereof. Methods of treatment and using organs, tissues and cells derived from such animals are also provided.