Nuclease-mediated methods for expanding repeats already present at a genomic locus are provided. Non-human animal genomes, non-human animal cells, and non-human animals comprising a heterologous hexanucleotide repeat expansion sequence inserted at an endogenous C9orf72 locus and methods of making such non-human animal cells and non-human animals through nuclease-mediated repeat expansion are also provided. Methods of using the non-human animal cells or non-human animals to identify therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative disorders associated with repeat expansion at the C9orf72 locus are also provided.

The present application provides peripheral blood mononuclear cells comprising an antigen, methods of manufacturing such PBMCs, and methods of using such PBMCs, such as for modulating an immune response in an individual. In some embodiments, the PBMCs are conditioned by incubating the PBMC in the presence of an adjuvant.

The present disclosure provides a genetically modified mouse comprising a genomic nucleic acid encoding human APOE4, a genomic nucleic acid encoding mouse TREM2 modified to include a R47H substitution, and at least one genomic modification selected from the group consisting of: (a) a genomic nucleic acid encoding mouse ABCA7 modified to include an A 1541 G substitution; (b) a genomic nucleic acid encoding mouse APP modified to include G60IR, F606Y, and R609H substitutions; (c) a genomic nucleic acid encoding mouse PLCG2 modified to include a M28L substitution; (d) a genomic nucleic acid encoding mouse MTHFR modified to include a A262V substitution; (e) an inactivated Ceacaml allele; and (f) an inactivated II1rap allele. Methods of producing the genetically modified mouse and methods of using the genetically modified mouse are also provided.

Methods and compositions are provided for activating transcription in a mammalian cell.

The present invention relates to vectors and compositions for the treatment of glycogen storage disease III.

The present disclosure relates to methods and compounds for promoting anabolic pathways in neuronal cells leading to improved neuronal survival. In particular, the present disclosure relates to inhibiting PHD to promote glycolysis and neuronal survival in a variety of neurodegenerative conditions such as retinitis pigmentosa.

The invention relates, in part, to methods to introduce gene alleles of interest into members of a population of a species. The invention also relates to methods to prepare large numbers of organisms comprising one or more introduced alleles of interest in an otherwise wild-type genome.

The present disclosure relates to genetically modified non-human animals expressing human or chimeric (e.g., humanized) Thrombopoietin (THPO), and methods of use thereof.

Compositions and methods for detecting nucleic acid-protein interactions, or more generally interactions between a nucleic acid and another molecule. A Cas protein (e.g., a catalytically dead Cas13) is fused to a proximity tagging enzyme (e.g., a Pup ligase) and thus brings the proximity tagging enzyme to the proximity of a protein that binds to a nucleic acid, when the Cas protein recognizes the nucleic acid, e.g., through a guide RNA. The proximity tagging enzyme then tags the protein enabling it to be identified as a protein that interacts with the nucleic acid.

The present application discloses methods of correcting a gene defect in a cell, methods of treating a patient having a disease or disorder characterized by a gene defect, methods of preparing a chimeric antigen receptor T cell, as well as systems for correcting a gene defect in a cell, ex vivo modified cells, and related compositions.