Provided for the first time in the present invention is a method for preparing a non-human primate somatic cell cloned animal, which method specifically comprises the steps of: (i) providing a reconstructed egg, wherein the egg comes from the non-human primate (ii) activating the reconstructed egg to form an activated reconstructed egg or activated reconstructed embryo formed by the reconstructed egg; (iii) reprogramming (a) the activated reconstructed egg or (b) embryonic cells of the activated reconstructed embryo to obtain a reprogrammed reconstructed egg or reprogrammed reconstructed embryo; and (iv) regenerating the reprogrammed reconstructed egg or reprogrammed reconstructed embryo to obtain the non-human primate somatic cell cloned animal. The method of the present invention can significantly improve the developmental capacity of nucleus-transplanted embryos in non-human primates (such as monkeys).

Fusion constructs are described. A fusion construct contains a peptide of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 28, fused to a peptide or protein (e.g., an antibody). As compared to the peptide or protein, fusion constructs exhibits improved penetration through the BBB, and are released on the abluminal surface of the BBB, after the post-luminal surface uptake. Fusion constructs could be used in drug discovery, diagnosis, prevention and treatment of diseases.

Methods, agents, and compositions for promoting milk production in a mammal are provided. Agents useful for promoting milk production may include an agent that inhibits NOTCH4 activity. The agent may inhibit NOTCH4 activity by binding to ROBO2 and/or by binding to NOTCH4. The agent may inhibit NOTCH4 by competing with ROBO1 for binding to ROBO2, thereby making ROBO1 available to inhibit NOTCH4 activity. The agent may be a soluble ROBO1 extracellular domain or an anti-NOTCH4 antibody that inhibits NOTCH4 activity. The agent may be an RNAi construct that inhibits expression of NOTCH4 or an RNAi construct that inhibits expression of ROBO2. Also provided herein are transgenic mammals genetically modified for expression of a soluble ROBO1 extracellular domain; inhibition of expression of ROBO2; and/or inhibition of expression of NOTCH4. Methods for promoting milk production in such transgenic mammals by administering one or more of the agents disclosed herein are also provided.

The present invention provides a disease model animal for tauopathies which reproduces the expression pattern of tau protein isoforms of adult human brain, that is, approximately equal amounts of 3R type tau and 4R type tau being expressed in the adult brain. The method for producing the disease model animal for tauopathies of the present invention comprises the steps of: preparing a tau seeds; and injecting the tau seeds in the brain of an animal carrying a mutation in the tau gene which fails to express the tenth exon. The animal carrying a mutation in the tau gene which fails to express the tenth exon may be produced by using any of the genome editing, gene targeting or base editing technologies.

The present invention relates to a pharmaceutical composition for preventing or treating cardiac arrhythmia. Particularly, the present invention relates to a pharmaceutical composition containing, as an active ingredient, a CCN5 protein or a nucleotide encoding the same. The pharmaceutical composition for preventing or treating cardiac arrhythmia, of the present invention, inhibits the pathological activity of CaMKII, which induces cardiac electrical abnormalities which is the main cause of atrial arrhythmia and ventricular arrhythmia, so as to restore the electrical functions, and inhibits the activity of myofibroblasts causing structural abnormalities. Therefore, the pharmaceutical composition of the present invention can be effectively used in the prevention or treatment of cardiac arrhythmia.

The application relates to methods for determining a parameter such as toxicity and pharmacokinetic behavior for a pharmaceutical compound against a disease or disorder. The test animals being used are non-human animals not suffering from or is not showing symptoms or signs of the disorder and which do not provoke an immune response against said pharmaceutical compound. These animals are obtainable by administration of a peptide comprising an oxidoreductase motif further comprising an NKT peptide epitope or an MHC class II T cell epitope of said pharmaceutical compound, wherein said motif and said epitope are separated by a linker of between 0 and 4 amino acids.

Described are methods and products related to the identification of multiple sclerosis (MS) as a transmissible protein misfolding disorder. Data is presented to support the position that the transmissible protein is an abnormal prion protein conformer (PrP.sup.MS). Methods are described for identifying a subject having, or at risk of developing, multiple sclerosis (MS) based on determining the presence or absence of PrP.sup.MS in a sample from the subject. The presence of the abnormal prion protein conformer in the sample is indicative of the subject having MS or an increased risk of developing MS. Also described are therapeutics methods for the treatment of MS as well as cell cultures, non-human animal models and biological samples thereof useful for the study of MS.

A method of modulating some or all copies of a gene in a cell is provided including introducing into a cell one or more ribonucleic acid (RNA) sequences that comprise a portion that is complementary to all or a portion of each of the one or more target nucleic acid sequences, and a nucleic acid sequence that encodes a Cas protein and maintaining the cells under conditions in which the Cas protein is expressed and the Cas protein binds and modulates the one or more target nucleic acid sequences in the cell.

Provided is a method for developing a secondary organ by using a non-human animal in which organ formation is inhibited, for the purpose of establishing a process for producing a functional cell such as a cell within the body of an animal such as a pig, the method including the step of raising a newborn or a fetus of the non-human animal in which organ formation is inhibited by complementing at least a part of the function of the organ whose formation is inhibited.

This disclosure describes exemplary embodiments of a method of creating a YY animal broodstock, preferably in a single generation, wherein the broodstock includes only sperm-producing YY males and egg-producing YY males, the method comprising the steps of: (a) creating YY males via androgenesis; (b) exposing selected ones of the YY males created in step (a) to a feminizing hormone; and (c) identifying sperm-producing YY males and egg-producing YY males from among the YY males created in steps (a) and (b). In other embodiments, the method further comprises: (d) repeating steps (a) through (c) N times in order to produce N unrelated families of sperm-producing YY males and egg-producing YY males; and (e) cross-breeding various ones of the unrelated families produced in step (d) in order to produce a genetically-diverse YY progeny. In some embodiments, N may be about 60.