Provided herein is technology relating to molecular biological manipulation of genes and genomes and particularly, but not exclusively, to CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) methods, compositions, systems, and kits for improved genetic editing.

The present invention features compositions and methods for recapitulating physiological X-chromosome inactivation (XCI) in a cell, including a cell of any embryo generated by Somatic Cell Nuclear Transfer (SCNT). In one aspect, the invention features a method for generating physiological X chromosome inactivation in an embryo generated by SCNT, the method comprising injecting the embryo generated via SCNT with an H3K27me3-specific demethylase polypeptide or a polynucleotide encoding said demethylase. Disclosed herein are methods, compositions, and kits comprising an agent which increases the expression of genes encoding an H3K27me3-specific demethylase, or increases the activity of human H3K27me3-specific demethylase.

Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Ago2 because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

The invention in some aspects relates to isolated nucleic acids, compositions, and kits useful for identifying adeno-associated viruses in cells. In some aspects, the invention provides kits and methods for producing somatic transgenic animal models using recombinant AAV (rAAV) to an animal having at least one transgene that expresses a small interfering nucleic acid or at least one binding site for a miRNA.

The present invention relates to a composition for treating neuroinflammatory disease comprising a complement component 8 gamma protein or a fragment thereof, and more particularly, to use for treating neuroinflammatory disease of a complement component 8 gamma protein or a fragment thereof which exhibits an effect of reducing the expression of inflammatory cytokines in microglia.

The composition of the present invention has effects of reducing Alzheimer's abnormal behavior patterns and reducing the secretion of neuroinflammatory cytokines in brain microglia and thus can be very usefully used for development of an agent for preventing or treating neuroinflammatory disease.

Provided are compositions and methods for inhibiting transmission of viruses that use mosquitoes as vectors, such as dengue (DENV), Zika (ZIKV) and Chikungunya (CHIKV) viruses. Inhibiting transmission includes reducing viral load of the virus in mosquitoes. The viral load is reduced in mosquitoes that are exposed to the virus by introducing into the mosquitoes or mosquito larvae one or more agents that can participate in RNA interference (RNAi) of expression of one or more mosquito genes, such as alpha-mannosidase 2, or Cadherin87A, or a combination thereof. Also provided are modified mosquitoes or mosquito larvae that comprise the RNAi agents. The modified mosquitoes can be released into a population of unmodified mosquitoes to inhibit transmission of the virus between mammalian hosts. Also provided are compositions comprising an RNAi agent or an expression vector that encodes the RNAi agent for use in the described methods.

This disclosure relates to genetically modified animals. More specifically, this disclosure relates to rodent animals in which an endogenous B4galt1 gene has been modified, e.g., to introduce a mutation that encodes an Asn to Ser substitution in the encoded B4galt1 protein at a position corresponding to position 352 in a human B4GALT1 protein, or to introduce a loss of function mutation (e.g., in a select tissue such as the liver). This disclosure also relates to use of such rodent animals in elucidating the role of B4galt1 in lipid metabolism.

The present application provides a novel drug screening platform designed to identify drugs that favorably modulate cellular bioenergetics in the human brain of a zebrafish which has been modified by altering a teleost gene that corresponds to a human gene associated with a brain dysfunction disorder (such as epilepsy). The drug screening platform are also useful for determining a mutation in a human gene associated with a brain dysfunction disorder that is associated with a human individual responsive to the treatment of a compound. Also provided are modified teleosts useful for the methods described herein.

A method of modulating some or all copies of a gene in a cell is provided including introducing into a cell one or more ribonucleic acid (RNA) sequences that comprise a portion that is complementary to all or a portion of each of the one or more target nucleic acid sequences, and a nucleic acid sequence that encodes a Cas protein and maintaining the cells under conditions in which the Cas protein is expressed and the Cas protein binds and modulates the one or more target nucleic acid sequences in the cell.

The present disclosure relates to compositions and methods of using the same for the treatment of various metabolic diseases and related disorders (e.g. diabetes mellitus, NAFLD, obesity, metabolic syndrome). The compositions and methods of the disclosure relate to the administration of an arginine-degrading enzyme.