The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems, wherein the guide sequence is modified by secondary structure to increase the specificity of the CRISPR-Cas system and whereby the secondary structure can protect against exonuclease activity and allow for 5 additions to the guide sequence.

The present invention provides cells, transgenic animals, including transgenic mammals and particularly rodents, comprising engineered immunoglobulin alleles. Mutations in the alleles are designed to compromise allelic exclusion and have potential to be exploited for the isolation of bispecific antibodies.

Genetically modified non-human animals comprising a humanized interleukin-15 (IL-15) gene. Cells, embryos, and non-human animals comprising a human IL-15 gene. Rodents that express humanized or human IL-15 protein.

The purpose of the present invention is to provide a set of two polypeptides for use in light-dependent genetic recombination in which the N-terminal side fragment and the C-terminal side fragment of a Cre protein having an amino acid sequence of SEQ ID NO: 1 respectively bind to two proteins light-dependently forming a dimer.

The present invention relates to a use of cellular repressor of E1A-stimulated genes (CREG) protein, and in particular to a use of a CREG protein or an active fragment thereof in manufacture of a medicament for the prevention and/or treatment of a fatty liver disease and type 2 diabetes. The present invention also relates to a use of a recombinant vector or recombinant cell expressing a CREG protein or an active fragment thereof in manufacture of a medicament for the prevention and/or treatment of a fatty liver disease and type 2 diabetes. The invention also relates to a corresponding kit, such as a kit used for the predication and/or evaluation of therapeutic effect and prognosis of a fatty liver disease and type 2 diabetes.

The present invention, in some embodiments thereof, is directed to a method for selecting a gender of an avian fertilized unhatched egg obtained from the crossing of a transgenic male avian subject and a transgenic female avian subject. Further provided is a kit for preparing a transgenic avian subject.

Provided are a protein complex in which estrogen receptor 2 (ERT2) is fused to CRISPR associated protein 9 (Cas9), and a recombinant vector carrying a gene coding the protein complex, wherein ERT2 is bonded to the N-terminus and C-terminus of nuclear localization sequence (NLS)-removed Cas9 and the complex has the advantage of translocating from the cytosol into the nucleus at a certain time point upon treatment with tamoxifen and modifying a specific DNA with the aid of guide RNA (gRNA), ultimately enabling a more elaborate DNA modification operation in a desired part at a desired time point.

Provided is a dielectric calibration technique using C2c1 endonuclease. The dielectric calibration technique is characterized by being especially applicable to eukaryotic cells, for example, to mammalian cells.

The present disclosure provides compositions and methods for controlling pain. The present disclosure provides methods for identifying agents that control pain.

A transgenic non-human animal model is disclosed. The system comprises an inducible transgene allowing the expression of a mutant POLG1 polypeptide that results in modulation of mitochondrial DNA copy number and/or concentration in the whole transgenic non-human animal or selected cells or tissues of the transgenic non-human animal. Methods of producing and using the model system are also provided.