This invention provides a method for knock-in of a donor DNA into the genome of a cell, comprising introducing at least one artificial nuclease system capable of cleaving target sequence(s) of the cell genome, the donor DNA, and two single-stranded oligonucleotides (ssODNs) into the cell, the artificial nuclease system cleaving the target sequence(s) on the cell genome, the two ssODNs each complementary to one of the ends generated by the target sequence cleavage in the cell genome and to one of the introduction ends of the donor DNA, the donor DNA being knocked-in at the cleavage site via the two ssODNs.

The present invention relates to cPLA2e inducing agents and cPLA2e inducing agents for use as a medicament, particularly for use in the treatment of a cognitive disorder and/or disease associated with a cognitive disorder, for example dementia, and more specifically age-related dementia and/or Alzheimer's disease.

The present invention provides an agent that enables Sirt7 gene expression, especially a recombinant adeno-associated virus (rAAV) that enables vascular endothelium (VE)-specific Sirt7 gene expression, and the use thereof. The present invention also provides a method for improving neovascularization, ameliorating aging features, extending lifespan and treating age-related diseases by using the agent, especially the rAAV.

The present disclosure relates to genetically modified animals that express a canine or chimeric (e.g., caninized) programmed cell death protein 1 (PD-1), and methods of use thereof.

Provided herein are compositions and methods for studying cancer therapeutics and etiology, for example, mouse cancer models, cancer cell lines, and uses thereof. Human p53 knock-in (Hupki) mice with a Y220 (e.g., Y220C, Y220H, or Y220S) mutation in p53 are provided. These Hupki-Y220 mice can be used, for example, to examine tumorigenesis in different tissues, investigate mechanisms of gain of function, develop mouse models of cancer, generate cancer cell lines that can be implanted into recipient mice, and test potential therapeutics.

A transgenic animal having a genome including a humanized immunoglobulin locus for securing the diversity of an antibody repertoire and a method of producing the same are disclosed. The transgenic non-human animal has two alleles of a humanized immunoglobulin gene, wherein the two alleles are hetero-alleles.

Methods and compositions are provided herein 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 and ex vivo. The methods and compositions employ cells and non-human animals comprising a Cas expression cassette such as a genomically integrated Cas expression cassette so that the Cas protein can be constitutively available or available in a tissue-specific or temporal-specific manner. Methods and compositions are also provided for making and using these non-human animals, including use of these non-human animals to assess CRISPR/Cas activity in vivo via adeno-associated virus (AAV)-mediated delivery of guide RNAs to the non-human animals.

Antibodies comprising unpaired variable domains, e.g., heavy chain variable (VH) domains, for binding antigen. Antibody comprising two immunoglobulin (Ig) chains, wherein a first Ig chain comprises a variable domain and a constant domain, and a second Ig chain comprises a constant domain, wherein the second Ig chain lacks a variable domain, leaving the variable domain of the first Ig chain unpaired. The antibody may comprise two Ig heavy chains and two Ig light chains, each heavy chain comprising a VH domain and a constant region comprising a CH1 domain, and each light chain comprising a CL domain, wherein one or both light chains lack a VL domain, thereby leaving one or both VH domains unpaired. Non-human animals (e.g., mice) engineered to produce antibodies having unpaired VH domains, involving deletion of sequence coding for light chain variable (VL) domains. Use of unpaired VH domains to generate antigen-binding molecules.

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with mutations in otoferlin (OTOF), by way of OTOF gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOF protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOF protein. These vectors can be used to increase the expression of OTOF in a subject, such as a human subject suffering from sensorineural hearing loss.

Disclosed herein are methods of treating HIBM in a subject comprising identifying subject in need thereof; and administering to the subject a compound, or a pharmaceutically acceptable salt, ester, amide, glycol, peptidyl, or prodrug thereof, wherein the compound is a compound that is biosynthesized in a wild type individual along a biochemical pathway between glucose and sialic acid, inclusive. Also disclosed herein are vectors comprising a nucleic acid sequence that encodes a polypeptide having at least 80% sequence identity to the sequence set forth in SEQ ID NO:2, recombinant cells comprising these vectors, and recombinant animals comprising the cells. In addition, methods of identifying a compound having therapeutic effect for HIBM are disclosed.