Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

Complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide are provided. Compositions and methods for delivery of complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide to mammals for both research and therapeutic use are provided. Methods of treating or reducing one or more symptoms of type 2 diabetes, prediabetes and/or gestational diabetes are provided.

The present disclosure generally relates to compositions and methods for improving the efficiency of homologous recombination. In particular, the disclosure relates to reagents and the use of such reagents.

The present invention relates to methods for treating patients having cancer or a premalignant or neoplastic condition. It is based, at least in part, on the discovery that a genome editing technique that specifically targets a fusion gene can induce cell death in a cancer cell other than a prostate cancer cell, e.g., a hepatocellular cancer cell, having the fusion gene. The present invention provides methods for treating cancer patients that include performing a genome editing technique targeting a fusion gene present within one or more cells of a subject to produce an anti-cancer effect.

Non-human animal cells and non-human animals comprising CRISPR/Cas synergistic activation mediator system components and methods of making and using such non-human animal cells and non-human animals are provided. Methods are provided for using such non-human animals to increase expression of target genes in vivo and to assess CRISPR/Cas synergistic activation mediator systems for the ability to increase expression of target genes in vivo.

A construction method for an immunodeficient rat model includes the following steps. The gRNAs targeted for knocking out a Prkdc gene and an IL2R gene are mixed with CAS9 mRNA respectively, and frozen in RNase-free ultrapure water to obtain injections A and B correspondingly. A human SIRP genomic DNA is amplified, purified, and frozen in RNase-free ultrapure water to obtain an injection C. The injections A and B are injected into cytoplasm of fertilized eggs of different rats, and the injection C is injected into a pronucleus of a fertilized egg of another rat. The three fertilized eggs are then transplanted into different pseudo-pregnant female rats to breed second-generation rats A, B and C, respectively. The second-generation rats A, B and C are intercrossed to breed an F1 generation; and the F1 generation is further intercrossed to obtain IL2R and Prkdc gene knockout immunodeficient rat models with human SIRP gene.

The present invention relates to a genetically edited animal, especially to a genetically edited pig in which expression or activity of the RELA protein has been modified. Such pigs have at least partial protection against the African Swine Fever Virus. The invention also provides, a cell nucleus, germ cell, stem cell, gamete, blastocyst, embryo, foetus and/or donor cell of a non-human animal comprising a genetic modification which alters the expression or function of RELA protein, methods for editing the genome of animals and methods for screening the efficacy of a pharmaceutical agent in such an animal.

Genetically modified non-human animals comprising a human or humanized interleukin-7 (IL-7) gene. Cells, embryos, and non-human animals comprising a human or humanized IL-7 gene. Rodents that express human or humanized IL-7 protein. Genetically modified mice that comprise a human or humanized IL-7-encoding gene in their germline, wherein the human or humanized IL-7-encoding gene is under control of endogenous mouse IL-7 regulatory sequences.

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

Provided herein are methods for generating modifiable, stable cell lines.