A hematopoietic stem cell (HSC), a hematopoietic progenitor cell (HPC) a myeloid/monocyte-committed progenitor cell, a macrophage or a monocyte comprising a vector wherein the vector comprises at least one mir-130a and/or mir-126 target sequence operably linked to a nucleotide sequence encoding interferon-alpha (IFN) for use in treating or preventing a cancer in a patient, wherein the HSC, the HPC, the myeloid/monocyte-committed progenitor cell, the macrophage or the monocyte is used in combination with an immune checkpoint inhibitor and/or a tumor associated antigen (TAA)-specific T-cell.

A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

Methods of producing an exogenous protein in a bird egg are provided according to aspects of the present invention which include: providing transfected avian primordial germ cells by forming a complex of Cas protein and a guide nucleotide sequence in the avian primordial germ cells, whereby a donor DNA sequence is inserted into genomic DNA of the avian primordial germ cells under transcriptional control of a regulatory element that directs tissue-specific expression of the exogenous protein; introducing the transfected avian primordial germ cells into a population of recipient bird embryos and incubating the recipient bird embryos, generating germline chimera birds; obtaining a heterozygote and/or homozygote transgenic bird by breeding the germline chimera bird; and isolating the exogenous protein from an egg laid by a female transgenic bird.

The present invention provides novel drug discovery platforms and methods for treating diabetes.

Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Programmed cell death 1 (Pdcd1) gene. The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).

A method for identifying an AhR-phospho-RORt protein complex inhibitor, comprising: (a) providing a cell culture, in which cells in the culture express AhR protein and phospho-RORt protein; (b) incubating the cell culture in the presence of a test agent; (c) assaying the level of the AhR-phospho-RORt protein complex in the presence of the test agent; (d) comparing the level of the AhR-phospho-RORt protein complex in the presence of the test agent with a control; and (e) identifying the test agent as the inhibitor of the AhR-phospho-RORt protein complex when the comparing step indicates that there is a reduction in the level of the AhR-phospho-RORt protein complex in the presence of the test agent as compared with the control. A method for identifying a GLKIQGAP1 protein complex inhibitor is also disclosed. Use of identified inhibitors in the manufacture of a medicament for treating a disease is also disclosed.

The present invention provides a rat embryonic stem cell characterized by having the following properties of (a) expressing Oct3/4 gene and Nanog gene, (b) positive for alkaline phosphatase activity, (c) having an embryoid body forming ability, (d) expressing SSEA (Stage-Specific Embryonic Antigen)-1 and SSEA-4, (e) having the same number of chromosomes as does a normal rat cell, (f) capable of being subcultured and holding the undifferentiated state, (g) having in vitro pluripotency, (h) having a potential to differentiate for cells of three embryonic germ lineages, (i) having teratoma formation ability, and (j) having an ability to produce a chimeric rat, a method of establishing the aforementioned rat embryonic stem cell and the like.

The present invention relates to genetically edited swine which produce CD163 protein in which the scavenger receptor cysteine-rich 5 (SRCR5) domain (also known as CD163 domain 5) has been deleted. Such swine have been found to be healthy and do not exhibit negative properties, and are resistant to PRRSV infection. CD163 expressed in the edited swine also demonstrates retention of the ability to function as a haemoglobin-haptoglobin scavenger. Methods of producing such swine are also provided.

The application concerns methods of treatment using anti-ErbB receptor antibody-maytansinoid conjugates, and articles of manufacture suitable for use in such methods. In particular, the invention concerns ErbB receptor-directed cancer therapies, using anti-ErbB receptor antibody-maytansinoid conjugates.