Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TTR locus comprising a V30M mutation 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 TTR locus express a human TTR protein or a chimeric TTR protein, fragments of which are from human TTR. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR.

In some aspects, the present invention provides chimeric transferrin receptor (TfR) polynucleotides and polypeptides. In other aspects, this invention provides chimeric TfR transgenic animal models and methods of using the animal models to identify therapeutics that can cross the blood-brain barrier.

The present invention provides PiggyBac transposase proteins, nucleic acids encoding the same, compositions comprising the same, kits comprising the same, non-human transgenic animals comprising the same, and methods of using the same.

The present discloses relates to a composition, a kit or a method using an eIF4E inhibitor for diagnosis or treatment of a condition associated with increased activity of eIF4E.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) TNFR2, and methods of use thereof.

Provided herein are compositions and methods for regenerating retinal ganglion cells (RGCs) from retinal neuron cells by activating transcription factors such as one or more of Atoh7, Brn3B, Sox4, Sox11, or Ils1. The retinal neuron cells may be interneuron cells such as amacrine cells, horizontal cells, and bipolar cell. The regenerated RGCs can project axons into discrete subcortical brain regions and establish retina-brain connections. They can respond to visual stimulation and transmit electrical signals into the brain. Therefore, the regenerated RGCs can replace damaged or degenerated RGCs, thereby treating vision impairment or blindness. The methods are likewise applicable to degenerated, damaged, or aged RGCs to stimulate them to regrow functional axons, thereby rejuvenating these RGCs.

Methods and compositions are provided for expanding coronary artery networks in an adult mammal in vivo, by increasing activity or expression of the transcription factor DACH1 in capillary endothelial cells. Compositions and kits for practicing the methods and/or for use with the systems of the disclosure are also provided.

The present invention relates to a method of treating a tauopathy in a subject, a method of improving cognitive ability in a subject suffering from cognitive impairment associated with a tauopathy, a method of reducing tau aggregates and neurofibrillary tangles. The method comprises administering an agent which promotes phosphorylation of tau at threonine in the sequence SSPGSPGTPGSRSR of the tau; and/or introduces a phosphomimetic of a phosphorylated tau, wherein the phosphorylated tau is tau that has been phosphorylated at threonine in the sequence SSPGSPGTPGSRSR of the tau.

The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

The present invention relates to methods for producing a non-human animal, such as an avian, comprising a targeted germline genetic modification, the method comprising: (i) delivering a programmable nuclease to sperm; (ii) fertilizing an ovum with the sperm, and (iii) generating the animal from the ovum, wherein the nuclease introduces the genetic modification into DNA of the sperm and/or the ovum.