The present invention includes compositions and methods for T cell genome editing and screening in vivo. In certain aspects, the invention includes an sgRNA library for genome-scale mutagenesis.

The present invention relates to an inhibitor of sphingolipids for use in the treatment or prevention of an aging related-disease and/or aging.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TRKB locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TRKB locus express a human TRKB protein or a chimeric transthyretin protein, fragments of which are from human TRKB. Methods are provided for using such non-human animals comprising a humanized TRKB locus to assess in vivo efficacy of human-TRKB-targeting reagents such as nuclease agents designed to target human TRKB.

A genetically modified rodent is provided that comprises a modified Acvr1 gene that comprises a conditional altered exon 7 encoding R258G in anti sense orientation, flanked by site-specific recombinase recognition sites, wherein the altered exon is inverted to sense orientation upon action of a recombinase, resulting in ectopic bone formation.

Disclosed is a method for stimulating neural tissue, where the neural tissue includes one or more neurons genetically modified to express a light-sensitive protein. The method comprises applying a light stimulus and an electrical stimulus to the neural tissue, thereby triggering membrane depolarisation in at least one of the neurons. Also disclosed is an apparatus for applying the disclosed method. The apparatus includes a light-stimulation device for selectively applying a light stimulus and an electrical-stimulation device for selectively applying an electrical stimulus to the neural tissue.

Genetically-modified zebrafish lacking one or more immune-related genes, and the use thereof, e.g., in cell or tissue transplantation methods or in stem cell biology. Tumors, tissues, and cells originating from zebrafish, other fish species, frogs, mouse, human, or other mammals can be readily engrafted into zebrafish that lack specific immune system regulatory genes. Here, described are zebrafish in which the entire genomic regions comprising the coding sequences of genes required for the development of T, B, and NK cells (including NK-lysin expressing cells) are deleted.

The present invention provides a non-human animal having human interleukin-34 (IL-34) in the body thereof; a method for producing a non-human animal having human microglia, which includes transplanting human CD34-positive hematopoietic stem cells into the non-human animal having human IL-34 in the body; and a method for producing human microglia, which includes obtaining human microglia from the non-human animal having human microglia.

An expression vector capable of disrupting the silencing of cell cycle genes in adult cells, such as adult cardiac myocytes and other quiescent cells in terminally differentiated tissues, comprising: (a) a nucleic acid sequence encoding lysine-specific demethylase 4D (KDM4D); (b) a promoter that induces or effects overexpression of KDM4D, wherein the promoter is operably linked to the nucleic acid sequence; and (c) a regulatory element that inducibly represses the overexpression of KDM4D. The vector can be administered to a subject in a method for inducing tissue-specific hyperplasia in a mammal, including cardiomyocyte proliferation. The method provides for regenerative therapy, including improving cardiac function after myocardial infarct and other forms of cardiac damage.

The invention is concerned with a fusion protein comprising interleukin 13 and a regulatory cytokine, for example, an interleukin chosen from interleukin 4, interleukin 10, interleukin 27, interleukin 33, transforming growth factor beta 1, transforming growth factor beta 2, and interleukin 13, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of a condition characterized by pathological pain, chronic pain, neuro-inflammation and/or or neurodegeneration.

A method of preparing a ddx27-deletion zebrafish mutant, including: determining a target of ddx27 knockout on a sixth exon of the ddx27 in a zebrafish and designing a gRNA sequence; using primers T7-ddx27-sfd and tracr rev for PCR amplification with a pUC19-gRNA scaffold plasmid as a template; purifying and transcribing the PCR product obtained in vitro to produce gRNA; introducing the gRNA and a Cas9 protein into the zebrafish; and culturing the zebrafish to obtain a zebrafish ddx27 mutant of stable inheritance. In addition, the application also discloses a phenotype of the ddx27-deletion zebrafish mutant, which plays an important role in investigating the biological function.