The present disclosure is directed, in some embodiments, to compositions and methods for inducible modification of a cell genome.

The present disclosure relates to an efficient genome editing technique. In one aspect, the technique can greatly improve the efficiency of homologous recombination during intracellular targeting, including gene targeting. Using this technique, genetically modified cell lines, rat, mouse, zebrafish, and fertilized eggs of other species can be quickly and efficiently generated.

Disclosed is CD31.sup.shed for use as a molecular imaging target in the molecular imaging of an inflammatory condition. Administering the radiolabeled peptide P8RI as CD31.sup.shed ligand in different rat models of inflammation indeed showed that CD31.sup.shed is present on activated cells in a quantity allowing a detectable signal, whereas the noise signal corresponding to CD31.sup.shed present on activated circulating cells and on other organs or cells not involved in inflammation was little. Also disclosed is a labeled CD31.sup.shed ligand and the use thereof as a molecular imaging agent in the molecular imaging of an inflammatory condition. The molecular imaging of inflammatory sites particularly allows determining whether a subject suffers from or is at risk of having an inflammatory condition or is at risk of recurrence of an inflammatory condition after an anti-inflammatory treatment.

Disclosed herein are methods and compositions for inactivating mutant genes associated with LCA, using engineered nucleases comprising a DNA binding domain and a cleavage domain or cleavage half-domain in conditions promoting the cleavage of the mutant genes. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases, and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.

An isolated rat liver cancer stem cell line which is named as TW-1 is provided. A method for drug screening by using the isolated rat liver cancer stem cell line is also provided.

Provided herein are methods and compositions for dynamically controlling and targeting multiple immunosuppressive mechanisms in cancer. Some aspects provide cells engineered to produce multiple effector molecules, each of which modulates a different immunosuppressive mechanisms of a tumor, as well as methods of using the cells to treat cancer, such as ovarian, breast, or colon cancer.

This invention relates to a transgenic non-human mammal whose genome comprises a polynucleotide sequence encoding a T cell receptor that is specific to a fluorescent protein, where the T cell of the non-human mammal comprises the T cell receptor. The present invention also relates to an isolated T cell from the transgenic non-human mammal of the present invention, an isolated T cell comprising an expression construct comprising a polynucleotide sequence that encodes a T cell receptor that is specific to a fluorescent protein, methods of making transgenic non-human mammals comprising T cell receptors that are specific to a fluorescent protein, a method of depleting cells in a non-human mammal using isolated T cells that encode a T cell receptor that is specific to a target protein, and a method of characterizing a T cell response to an agent.

Cells, including stem cells, comprising an autobioluminescent phenotype, wherein the cells emit a luminescent signal in the absence of an exogenous luminescent stimulator, are provided. The luminescent signal may be constitutive, inducible, repressible, or tissue-specific. The cells express a synthetically engineered bacterial luciferase (lux) cassette, i.e., the luxCDABEfrp gene cassette. The cells may comprise luxA, luxB, luxC, luxD, luxE, and flavin reductase. The cells may each express a combined expression level of luxC, luxD, luxE, and flavin reductase that is from ten to forty times greater than a combined expression level of luxA and luxB. Further, methods of making and using the cells comprising an autobioluminescent phenotype are disclosed herein.

Described herein are methods and uses thereof for in vivo evaluating functions of multiple genes in parallel by combining in utero genetic perturbation of progenitor cells and single-cell transcriptomic profiling of progeny cells in animals. These methods can be used, among other things, to reveal in vivo gene functions in a cell type-specific manner.

Methods and compositions are provided for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo or ex vivo. The methods and compositions employ non-human animals comprising a CRISPR reporter such as a genomically integrated CRISPR reporter for detecting and measuring targeted excision of a sequence between two CRISPR/Cas nuclease cleavage sites or disruption of a sequence near a CRISPR/Cas nuclease cleavage site and/or measuring CRISPR/Cas-induced recombination of the CRISPR reporter with an exogenous donor nucleic acid to convert the coding sequence for a first reporter protein to the coding sequence for a different second reporter protein. Methods and compositions are also provided for making and using these non-human animals.