Provided a method of treating ocular surface damage caused by an eye disease or eye injury like dry eye disease, chemical or physical injury, infection, neurosensory abnormalities and unspecified etiologies in a subject, comprising administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of microRNA-328 antagonist.

Provided is a genetically modified non-human mammal that comprises an anchor DNA sequence inserted at an endogenous locus of a secretory milk protein gene, wherein the anchor DNA sequence comprises a site-specific recombinase recognition site. Also provided is a genetically modified non-human mammal that comprises a transgene inserted at an endogenous locus of a secretory milk protein gene, wherein the transgene encodes a secretory protein and is operably linked to the endogenous promoter of said secretory milk protein gene, and wherein the transgene is flanked by a pair of site-specific recombinase resulting sites. The genetically modified non-human mammals provided can be used for producing the secreted recombinant protein encoded by the transgene from the milk produced by the genetically modified non-human mammals.

Methods, uses, and compositions for manipulating genomic DNA. Some of the embodiments of the invention provide for making a founder animal that is completely free of all unplanned genetic modifications. Some embodiments are directed to removing genetic faults in established breeds without making other alterations to the genome. Other embodiments are directed to particular tools or processes such as TALENs or CRISPR with a preferred truncation. One embodiment involves introducing a targeted targeting endonuclease system and a HDR template into a cell (optionally with a mismatch in the binding of the targeting endonuclease and the targeted site). Another embodiment includes processes of making a genetically modified livestock animal comprising a genome that comprises inactivation of a neuroendocrine gene selective for sexual maturation, with the inactivation of the gene preventing the animal from becoming sexually mature. One embodiment includes compositions and methods for making livestock with a polled allele, including migrating a polled allele into a bovine species without changing other genes or chromosomal portions.

The present application provides genetically modified non-human animals and methods for producing heavy chain-only antibodies (HcAbs), wherein the genetically modified non-human animal comprises a germline genome comprising an engineered immunoglobulin heavy chain (IgH) allele at an endogenous IgH locus, wherein the engineered IgH allele lacks functional gene segments encoding CH1 domains of all endogenous IgG subclasses. In some embodiments, a genetically modified mouse is provided, comprising an engineered IgH allele that lacks a functional endogenous gene segment encoding C3, C1, C2b and CH1 exon of C2c. Further provided are HcAbs or derivatives thereof produced by the genetically modified non-human animals.

The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Ig and/or Ig sequences. Of particular interest are animals with transgenic heavy and light chain immunoglobulin loci capable of producing a diversified human(ized) antibody repertoire that have their endogenous production of Ig and/or endogenous Ig and/or Ig sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Ig and/or Ig results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

The object of the present invention is to provide a test method using a novel administration method of an extract from inflamed tissues inoculated with vaccinia virus or a preparation containing the extract. It has been demonstrated that by sustainedly administering an extract from inflamed tissues inoculated with vaccinia virus or a preparation containing the extract by using a continuous administration device according to the present invention, a comparable effect is exerted at a very low dose compared with conventional administration methods such as oral administration. Therefore, the present invention can provide a test method using animals requiring less burden on a researcher, a treatment of patient at a low dose, and the like.

The present invention relates to a method of assessing pharmacokinetic properties of a variant of human serum albumin using a non-primate animal species where the native albumin of the animal provides minimal competition for HSA binding to the FcRn receptor in said animal. In the non-primate animal species, the binding affinity of wild type HSA to the native FcRn of said animal is the same as or higher than the binding affinity of the native albumin of said animal to the native FcRn. The present invention also relate to animal models which are particularly suitable for assessing pharmacokinetics of human serum albumin variants.

Herein is reported a transgenic vector comprising a humanized light chain locus, wherein said humanized light chain locus comprises (a) a V gene segment derived from human light chain V segment IGKV1-39-01, (b) 3 proximal to said light chain gene segment a promoter, and (c) 5 proximal to said light chain gene segment at least a fragment of the human IGKJ4 J-element.

The present invention provides a genetically modified non-human organism in which an expression level of Cas9 is high and a plurality of different genes or different locations in the same gene can be edited at the same time with high efficiency. The genetically modified non-human organism includes a nuclear genome having at least 3 copies of genes that code for Cas9 (CRISPR-associated 9). Egg cells of the present invention are derived from the genetically modified non-human organism having the nuclear genome into which at least 3 copies of genes that code for the Cas9 are introduced. Fertilized eggs of the present invention are obtained by fertilizing the egg cells and sperm derived from the same species of the organism. A method for modifying target genes includes a step of introducing a guide RNA into cells derived from the genetically modified non-human organism, the egg cells, or the fertilized eggs.

The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Ig and/or Ig sequences. Of particular interest are animals with transgenic heavy and light chain immunoglobulin loci capable of producing a diversified human(ized) antibody repertoire that have their endogenous production of Ig and/or endogenous Ig and/or Ig sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Ig and/or Ig results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.