The invention relates to nucleic acid constructs for expression in mice for the production of heavy chain only antibodies and V.sub.H domains, transgenic mice, related methods and uses.

Genetically modified non-human animals are provided that exhibit a functional lack of one or more lncRNAs. Methods and compositions for disrupting, deleting, and/or replacing lncRNA-encoding sequences are provided. Genetically modified mice that age prematurely are provided. Also provided are cells, tissues and embryos that are genetically modified to comprise a loss-of-function of one or more lncRNAs.

A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.

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.

This document relates to non-human animal models (e.g., non-human mammalian models such as mouse models) for aging (e.g., neural aging). For example, non-human animal models having reduced or eliminated levels of aralkylamine N-acetyltransferase (AANAT) polypeptide expression are provided.

A method for screening an active ingredient of a saltiness enhancer, the screening method including the following steps: (i) a step for determining whether a test substance is a compound capable of promoting functional expression of the TMC4 gene or TMC4 protein; and (ii) a step for selecting, as an active ingredient of a saltiness enhancer, a test substance that has been determined in step (i) to be a compound capable of promoting functional expression of the TMC4 gene or TMC4 protein.

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.

A transgenic chicken comprising an inactivated heavy immunoglobulin gene and/or inactivated light chain immunoglobulin gene is provided, as well as cells and targeting vectors for making the same.

The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

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.