The present invention relates to nucleic acid constructs, viral vectors and viral particles comprising a transgene encoding GAT-1; and use of such viral particles for treating diseases mediated by SLC6A1-impairment.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

Provided herein is a next-generation highly-efficient technology that can be used for biocontrol of D. suzukii and/or Aedes aegypti. The composition and technique termed precision guided SIT (pgSIT) functions by exploiting the precision and accuracy of CRISPR to simultaneously disrupt genes essential for either female viability or male fertility. It utilizes a simple breeding scheme requiring two homozygous strains—one expressing Cas9 and the other expressing double guide RNAs (dgRNAs). A single mating between these strains mechanistically results in synchronous RNA-guided dominant biallelic knockouts of both target genes throughout development, resulting in the complete penetrance of desired phenotypes in all progeny. This document provides methods and compositions relating to producing such insect eggs, insects, insect populations and uses thereof in reducing a wild-type insect population, along with methods and materials for producing genetically modified progeny of D. suzukii and/or Aedes aegypti.

Compositions and methods for in utero gene editing in mammalian lung cells are disclosed.

Aspects of the disclosure relate to methods and compositions for diagnosing and/or treating idiopathic Normal Pressure Hydrocephalus (iNPH). In some embodiments, the methods comprise detecting a level of Cwh43 gene expression or Cwh43 protein in a subject and administering to the subject one or more therapies to treat iNPH based upon the level of the Cwh43 gene expression or Cwh43 protein compared to a control sample.

Application of a fragment of an isolated nucleotide sequence in the construction of zebrafish without intermuscular bones. The nucleotide sequence is shown in SEQ ID NO:1. Gene mutation is performed by taking SEQ ID NO:1 as a target gene; the mutant F0 embryos are selected and cultured to adult fish; F0 mutant is hybridized with wild type zebrafish to generate an F1 embryos; sense mutant heterozygotes F1 is screened out and cultured to adult fish; and then F1 heterozygote self-crosses to generate F2 generation of three gene types, including homozygote, heterozygote, and wild type. Zebrafish without intermuscular bones is obtained by using a gene mutation method, which provided a basis for subsequent research on a molecular formation mechanism of fish intermuscular bones and the cultivation of economic fishes without intermuscular bone and possessed a basic research value and an application value in other economic aquaculture fish species.

Provided are genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL33, and methods of use thereof.

The present disclosure provides rodent models of increased bone mineral density and/or bone mineral content, genetically modified rodents and isolated rodent cells or tissues having a disruption of one or both alleles of the Zinc and Ring Finger 3 (Znrf3) gene, knockout rodent Znrf3 DNA constructs, methods of producing genetically modified rodents, methods of producing Znrf3 knockout rodents, and methods of determining the effect of an agent for treating low bone mineral density and/or bone mineral content.

Provided is the use of an ECM1 gene-knockout mouse in the screening of an anti-hepatic fibrosis drug. Specifically, provided is a method for preparing an animal model of hepatic fibrosis or related diseases thereof in non-human mammals, which method comprises the following steps: (a) providing a non-human mammalian cell and inactivating an ECM1 gene in the cell, thereby obtaining a non-human mammalian cell in which the ECM1 gene is inactivated; and (b) using the cell in which the ECM1 gene is inactivated obtained in step (a) to prepare an animal model of hepatic fibrosis or related diseases thereof in which the ECM1 gene is inactivated. The animal model is an effective animal model of hepatic fibrosis or related diseases thereof, may be used for studying hepatic fibrosis or related diseases thereof, and may be used in the screening and testing of a particular drug.

The present invention relates to a small activating nucleic acid molecule for treating spinal muscular atrophy and use thereof. The small activating nucleic acid molecule comprises a sense nucleic acid strand and an antisense nucleic acid strand, wherein the sense nucleic acid strand and the antisense nucleic acid strand are independently an oligonucleotide strand of 16 to 35 nucleotides in length, in which one nucleotide strand has at least 75% base homology or complementarity to a target selected from a promoter region of a target gene SMN2. The present invention also relates to a pharmaceutical composition comprising the small activating nucleic acid molecule disclosed herein and optionally, a pharmaceutically acceptable carrier, and a method for up-regulating the expression of a target gene in cells and methods for treating a disease induced by insufficient expression of a target gene with the small activating nucleic acid molecule or the pharmaceutical composition comprising the small activating nucleic acid molecule disclosed herein.