Methods are disclosed for enhancing growth of a human acute myeloid leukemia (AML) sample, a human myelodysplastic syndrome (MDS) sample, a human IL-8 dependent tumor sample, human preleukemia cells, and a human preleukemia clone or subclone ex vivo or in a xenograft animal model comprising adding human interleukin-8 (hIL-8) or a hIL-8 agonist to the sample or administering hIL-8 or a hIL-8 agonist to the animal model or expressing a gene encoding hIL-8 or a hIL-8 agonist in the animal model. The invention also provides a transgenic animal that expresses a gene encoding human interleukin-8 (hIL-8) or a hIL-8 agonist, which can be used to test the effectiveness of treatments for AML, MDS and IL-8 dependent tumors.

The invention provides inducible promoter systems and their components incorporating components of a tetracycline operon. By coordinating expression of different transcriptional units in these systems as a result of selection of promoters and/or linking the units into the same DNA molecule, these systems can achieve higher levels of expression of coding segments of interest, increased differential levels of expression between on- and off-states, and/or greater responsiveness to inducing agents than conventional systems.

Disclosed are compositions, methods, and kits for modifying DNA within cells as well as compositions and methods for modifying gene expression in a cell. In particular, the invention generally relates to compositions, methods, and kits for DNA editing using single-stranded DNA. Compositions and methods for modifying gene expression using artificial microRNAs (amiRNA) are also contemplated.

Livestock animals and progeny thereof comprising at least one edited chromosomal sequence that alters expression or activity of a somatostatin receptor (SSTR) protein are provided. Livestock animal cells that contain such edited chromosomal sequences are also provided. The livestock animals have improved growth performance and weight gain. Methods for producing livestock animals with increased growth performance are also provided.

Provided herein are methods and compositions for treating an eye disorder, for example cone-rod dystrophy type 6 (CORD6). In certain aspects, a therapeutically effective amount of a composition comprising nucleic acids is administered to a subject to treat an autosomal dominant disorder or condition, such as a condition associated with a dominant mutation in a guanylate cyclase 2D (GUCY2D) gene, such as knocking out a dominant mutant form of the gene in the subject. Further provided herein are recombinant AAV particles that comprise one or more recombinant AAV genomes comprising nucleic acids that encode a guide RNA that targets a GUCY2D gene and/or an RNA-guided endonuclease.

The present subject matter relates to the use of one or more inhibitors to treat a disease, e.g., cancer, in a subject. It is based, at least in part, on the discovery that protein kinase B (AKT) and ring finger protein 167 (RNF167)-mediated CASTOR1 degradation activates the mammalian target of rapamycin complex 1 (mTORC1) independent of arginine and promotes cancer progression. Accordingly, the presently disclosed subject matter provides for compositions, methods, and kits for treating a subject using an RNF167 inhibitor, an inhibitor that reduces phosphorylation of CASTOR1 at S14, ubiquitination and/or degradation of CASTOR1, or a combination thereof.

Disclosed are compositions, methods, and kits for modifying DNA within cells as well as compositions and methods for modifying gene expression in a cell. In particular, the invention generally relates to compositions, methods, and kits for DNA editing using single-stranded DNA. Compositions and methods for modifying gene expression using artificial microRNAs (amiRNA) are also contemplated.

A knock-in non-human mammal comprising a recombinant androgen receptor (AR) cassette containing an exogenous human polyglutamine (polyQ) tract encoding sequence in exon 1, wherein the human polyQ tract encoding sequence is stably integrated into the genome of the animal. Also provided are recombinant cells, fertilized eggs and tissues. The resulting animal displays a wide range of phenotypes, best characterized as Metabolic Syndrome and can be used in screening and other assays.

The invention provides inducible promoter systems and their components incorporating components of a tetracycline operon. By coordinating expression of different transcriptional units in these systems as a result of selection of promoters and/or linking the units into the same DNA molecule, these systems can achieve higher levels of expression of coding segments of interest, increased differential levels of expression between on- and off-states, and/or greater responsiveness to inducing agents than conventional systems.

A genetically modified non-human animal in which an auxin-inducible degron system controls degradation of a target protein in a living body includes: a chromosome containing a first nucleic acid that encodes a mutant TIR1 family protein having a mutation at an auxin-binding site and having affinity to an auxin analog.