The instant invention relates to transgenic non-human animals capable of producing heterologous antibodies, transgenes used to produce such transgenic animals, transgenes capable of functionally rearranging a heterologous D gene in V-D-J recombination, immortalized B-cells capable of producing heterologous antibodies, methods and transgenes for producing heterologous antibodies of multiple isotypes, methods and transgenes for producing heterologous antibodies wherein a variable region sequence comprises somatic mutation as compared to germline rearranged variable region sequences, transgenic nonhuman animals which produce antibodies having a human primary sequence and which bind to human antigens, hybridomas made from B cells of such transgenic animals, and monoclonal antibodies expressed by such hybridomas.

An expression vector capable of disrupting the silencing of cell cycle genes in adult cells, such as adult cardiac myocytes and other quiescent cells in terminally differentiated tissues, comprising: (a) a nucleic acid sequence encoding lysine-specific demethylase 4D (KDM4D); (b) a promoter that induces or effects overexpression of KDM4D, wherein the promoter is operably linked to the nucleic acid sequence; and (c) a regulatory element that inducibly represses the overexpression of KDM4D. The vector can be administered to a subject in a method for inducing tissue-specific hyperplasia in a mammal, including cardiomyocyte proliferation. The method provides for regenerative therapy, including improving cardiac function after myocardial infarct and other forms of cardiac damage.

Methods and compositions using a nucleic acid molecule encoding an atonal-associated factor in combination with a co-transcription factor and/or inhibitor of a gene silencing complex to change the sensory perception of an animal are described.

The invention relates to a method of expanding a population of regulatory T cells in a tissue or organ of a subject, wherein said method comprises administration of IL-2 and a targeting moiety specific for said tissue or organ, and wherein said tissue or organ is the central and/or peripheral nervous system. The invention further relates to populations of regulatory T cells produced according to the method and the production of said population in vivo. Also provided is a pharmaceutical composition comprising IL-2 and a targeting moiety as defined herein as well as a method of treating a disease or disorder mediated by inflammation or for the reduction of inflammation which comprises the methods defined herein or administration of a pharmaceutical composition as defined herein.

Provided herein are recombinant vectors that express bivalent binding members and methods of using the vectors to modify cells of the nervous system to express the binding members in the brain of patients having a neurological disease such as a neurodegenerative disease.

The present disclosure is directed to transgenic animals (e.g., transgenic porcine animals) comprising multiple genetic modifications that advantageously render these animals suitable donors for xenotransplanation. The present disclosure extends to organs, organ fragments, tissues and cells derived from these animals and their therapeutic use. The present disclosure further extends to methods of making such animals. In certain embodiments, the transgenic animals (e.g., transgenic porcine animals) have reduced expression of the growth hormone receptor (GHR) gene or have impaired function of the GHR protein.

Provided is a method for more efficiently sorting out genetically modified cells. Specifically provided are a method for selecting a cell including a modified gene on a target locus in a genome, a method for producing a cell including a modified gene on a target locus in a genome, and an animal including a modified gene on a target locus in a genome, and a kit for selecting an animal including a modified gene on a target locus in a genome and cells including a modified gene on a target locus in a genome.

This invention relates to a transgenic animal model for testing immunogenicity and protective efficacy of human vaccines and the method for generating such a multi-transgenic animal. This invention also relates to methods for screening compositions for human vaccine development. More specifically, the present invention relates to a mouse model capable of expressing human leukocyte antigens DR4 and A2, and/or human costimulatory molecules (CD80) which upon infusion of human HLA-matched hematopoietic stem cells develop a functional human immune system able to respond to vaccination with human vaccines. The invention also relates to method of producing human antibodies specific for a desired antigen using the transgenic mouse.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric OX40, and methods of use thereof.

The present invention relates to transgenic ornamental barbs, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic barbs and methods of providing them to the ornamental fish industry for the purpose of marketing.