A method of constructing a zebrafish notch1a mutant using CRISPR/Cas9 technique. The method includes: determining a target for knocking out notch1a; using primers T7-notch1a-sfd and tracr rev for PCR amplification with a pUC19-gRNA scaffold plasmid as a template; transcribing PCR product in vitro followed by purification to obtain gRNA; and microinjecting the gRNA and a Cas9 mRNA into a zebrafish embryo followed by culture to obtain an notch1a mutant of stable inheritance. The invention selects a specific target and utilizes CRISPR/Cas9 technique to knock out the notch1a in the zebrafish without destroying other genes, generating the zebrafish notch1a mutant. Moreover, the invention also discloses the phenotype of the zebrafish notch1a mutant, which plays a significant role in studying the effect of the Notch1a receptor in the Notch signaling pathway.

Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

Provided herein are compositions and methods of use thereof for screening a plurality of uniquely identifiable therapeutic moiety in vivo by identifying one or more reporters indicative of a cell state.

A system for controlling population of a biological species includes a population of genetically-modified individuals of the biological species, where both males and females in the genetically-modified population carry two mutations. The first mutation is a repressible genetic mutation that results in death of a juvenile individual of the first sex when the juvenile individual of the first sex comprises the repressible lethal mutation and is reared in the absence of a repressor or causes an individual to be sterile when reared in the absence of a repressor. The second mutation is an underdominant genetic mutation.

The present disclosure provides compositions and methods for increasing resistance to PCV2 infection in pigs. The increased resistance may be the result of siRNA or genetic modification through CRISPR or a vectored virus targeting SNPs that are resistant to PCV2 infection.

Method for controlling for the appearance of seizures in the mammalian brain comprising modifying the abundance of a specific miRNA—miR-211, for uses in preventing seizures and providing a model system to examine the effect of a drug or a treatment to seizures.

Provided herein are methods for treating a disease or disorder associated with mitochondrial dysfunction through ex vivo introduction of a nucleic acid molecule into hematopoietic stem and progenitor cells (HSPCs) followed by transplantation of the HSPCs into a subject in need of treatment. The nucleic acid molecule may include a functional human frataxin (hFXN) or may include a gene editing system that when transfected into the cells removes a trinucleotide extension mutation of endogenous hFXN.

Provided herein are transgenic non-human animals whose genomes comprise two or more human genes selected from CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16, to methods of screening candidate agents that bind to and/or modulate the function and/or activity of at least one of the human genes in the transgenic non-human animals, and to methods of screening candidate agents to determine their effect on one or more activities and/or functions associated with expression of at least one of the human genes in the transgenic non-human animals. Further provided herein are methods of recapitulating a human Siglec immune system in a non-human animal, and methods of generating a non-human animal disease model comprising a human Siglec repertoire.

The present inventors have conducted intensive studies on an antibody which controls HIV in an administration group with a high probability over a long period of time with one or several times of single-agent administration. As a result, the present inventors have surprisingly found that, when an SW-1C10 antibody, which is obtained by producing an antibody gene reported as 1C10 in silkworms, is singly administered only a few times, the viral load in the blood is suppressed to the detection limit or lower at an early stage in all of individuals to which the antibody has been administered, and moreover, the viral RNA load in the blood is maintained at the detection limit or lower for a long time of 12 weeks. Also, the yield of the antibody in silkworms is approximately several hundreds μg per cocoon, or several μg per 1 mg of cocoon, and studies to increase the productivity more than this level have not been conducted heretofore. The present inventors have conducted studies to find an antibody having a higher yield in silk-spinning insects among a large number of anti-HIV antibodies. As a result, the present inventors have found that a 1C10 antibody and a 1D9 antibody, each of which is an anti-HIV antibody, are produced in silk threads of silk-spinning insects at a higher yield than the conventional yield.

The present specification relates to a transgenic animal and a transgenic embryo producing components of an engineered nuclease.

According to the disclosure of the present specification, the transgenic animal (or embryo) producing components of an engineered nuclease is a transgenic animal (or embryo) which includes a first cell having a genome including a first toolbox; and a second cell having a genome including a second toolbox, wherein the first toolbox and the second toolbox include at least one of a polynucleotide encoding an RNA-guided endonuclease and a polynucleotide encoding a guide nucleic acid that is able to specifically bind to a target site, respectively, wherein the first toolbox is present in a first locus of the genome of the first cell; the second toolbox is present in a second locus of the genome of the second cell; and the first locus is different from the second locus.