Abstract: 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.

Abstract: Provided herein are recombinant cardiomyocytes and cardiomyocyte cell lines expressing human Ether-a-go-go Related Gene (hERG) potassium ion channel, including, for example, stable cell lines, that comprise a transfected or transduced nucleic acid sequence encoding hERG. Also provided herein are methods of using the recombinant cardiomyocytes and cardiomyocyte cell lines expressing hERG for screening compounds for cardiotoxicity, including methods for determining the activity of compounds to inhibit hERG.

Abstract: The present invention discloses a method for assessing the capacity of a substance to treat or prevent hepadnavirus infection. A reporter virus carrying genetic information for a first fragment of a recombinase and a reporter cell expressing a second fragment of the recombinase are used. When the reporter virus infects the reporter cell, the two fragments of the recombinase associate and excise a stop cassette that is flanked by two recombination sites and blocks the expression of a reporter gene. Accordingly, the present invention relates to a method of assessing the capacity of a substance to treat or prevent hepadnavirus infection, a hepadnavirus comprising a nucleic acid encoding a first fragment of a recombinase and a mammalian hepatocyte or hepatoma cell comprising a nucleic acid encoding a second fragment of a recombinase and a nucleic acid comprising a stop cassette flanked by two recombination sites fused to a reporter gene.

Abstract: Disclosed herein are compositions and methods that involve using compositions containing one or more of ETV2, FOXC2, FLI1 and a miR-200b inhibitor for directly reprogramming somatic cells into induced vasculogenic cells both in vitro and in vivo. These compositions and methods are useful for a variety of purposes, including the development of pro-angiogenic therapies.

Abstract: This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention a transgene product is delivered to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the brain. The viral vector delivers the transgene to a region of the brain which is susceptible to infection by the virus and which expresses the encoded recombinant viral gene product. Also provided are compositions for delivery of a transgene product to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the subject's brain.

Abstract: A chimeric antigen receptor, comprising an amino acid sequence shown in SEQ ID NO. 1. A nucleic acid encoding the chimeric antigen receptor, a vector comprising the nucleic acid, an immune effector cell comprising the chimeric antigen receptor, the nucleic acid molecule and/or the vector, a method for preparing the immune effector cell, a composition comprising the immune effector cell, and use of the chimeric antigen receptor.

Abstract: The present invention relates to a method for producing an animal model of preterm birth and an animal model of preterm birth produced by the method. The animal model of the present invention can be effectively applied to investigate the causes and symptoms of preterm birth induced by cervical injury. The mortality rate of the animal model according to the present invention is low until preterm birth despite its induced preterm birth. In addition, the animal model of the present invention is produced in a higher yield than any other existing model. Furthermore, the preterm birth of the animal model according to the present invention is induced at a desired time point. Due to these advantages, the animal model of the present invention can be effectively applied to investigate the causes and mechanisms of preterm birth. The mortality rate of premature neonates born from the animal model of the present invention is considerably low and the premature neonates are immature.

Abstract: The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease. As a preferred example, the present disclosure relates to fusion polypeptides comprising (a) a first polypeptide comprising a first secretion signal, a first multimerization domain, a first transmembrane domain, and an actuator domain, (b) a viral self-cleaving polypeptide, and (c) a second polypeptide comprising a second secretion signal, a binding domain that comprises a single chain antibody, a receptor ectodomain, or a ligand, a second multimerization domain, and a second transmembrane domain.

Abstract: Disclosed herein are compositions and methods that involve using compositions containing one or more of ETV2, FOXC2, FLI1 and a miR-200b inhibitor for directly reprogramming somatic cells into induced vasculogenic cells both in vitro and in vivo. These compositions and methods are useful for a variety of purposes, including the development of pro-angiogenic therapies.

Abstract: The present disclosure relates to materials, formulations, production methods, and methods for delivery of CFTR mRNA, including but not limited to chemically modified mRNA for induction of CFTR expression, including in the mammalian lung. The present invention is particularly useful for treating cystic fibrosis, but is also useful in the treatment of diseases related to CFTR gene.

Abstract: An expression construct is disclosed which comprises: (i) a DNA sequence which encodes at least one guide RNA (gRNA) operatively linked to a transcriptional regulatory sequence so as to allow expression of the gRNA in a target cell; (ii) a barcode sequence for identification of the at least one gRNA operatively linked to a transcriptional regulatory sequence so as to allow expression of the barcode sequence in the target cell.

Abstract: Provided herein are transgenic non-human animals whose genomes comprise two or more human genes selected from TREM1, TREML1, TREM2, TREML2, and TREML4, 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 TREM immune system in a non-human animal, and methods of generating a non-human animal disease model comprising a human TREM repertoire.

Abstract: The present invention relates to compositions and adeno associated viral vectors comprising an optimised HGSNAT nucleic acid sequence of SEQ ID No. 1 or a derivative sequence having at least 77% homology thereof. Uses of such compositions and vectors are also contemplated along with kits of parts for their administration.

Abstract: The present disclosure provides methods and compositions useful for the treatment or prevention of heart disease. In particular, the present disclosure provides a vector comprising a modified troponin T promoter operatively linked to a therapeutic gene product for the treatment or prevention of heart disease, e.g., cardiomyopathy. The gene product may be MYBPC3. The disclosure also provides recombinant adeno-associated virus (rAAV) virions, rAAV viral genomes, and expression cassettes and pharmaceutical compositions thereof. The disclosure further provides methods for treating a disease or disorder, such as heart disease.

Abstract: The subject invention pertains to a Molecular Cell Diary System (MCDS), which allows identification of the history of somatic alterations in the cell. MCDS comprises one or more combinations of a DNA cutter and a DNA writer expressed under the control of a promoter controlled a cellular event of interest. The DNA cutter and the DNA writer are in a combination are co-expressed when an even of interest occurs. The DNA cutter creates double strand breaks (DSB) in a target DNA in a sequence specific manner and the DNA writer incorporates DNA sequences in the DSB. The endogenous DNA repair machinery synthesizes repairs the DSB. As such, the combination of the DNA cutter and the DNA writer modifies the target DNA and leaves “marks” of the occurrence of the cellular event of interest. These marks are sequenced and the cellular event history of the cell is deciphered.

Abstract: Methods and constructs for engineering circular RNA are disclosed. In some embodiments, the methods and constructs comprise a vector for making circular RNA, the vector comprising the following elements operably connected to each other and arranged in the following sequence: a.) a 5? homology arm, b.) a 3? group I intron fragment containing a 3? splice site dinucleotide, c.) optionally, a 5? spacer sequence, d.) a protein coding or noncoding region, e.) optionally, a 3? spacer sequence, f) a 5? Group I intron fragment containing a 5? splice site dinucleotide, and g.) a 3? homology arm, the vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. Methods for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector are also disclosed.

Abstract: Compounds that either produced a higher proportion or greater absolute number of phenotypically identified nave, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies with improved efficacy are provided.

Abstract: This invention relates to compositions of matter, methods, modules and instruments for automated mammalian cell growth and mammalian cell transduction followed by nucleic acid-guided nuclease editing in live mammalian cells. The present compositions and methods entail viral delivery of an editing cassette to live mammalian cells such that the editing cassettes edit the cells and the edited cells continue to grow, preferably using a fully-automated end-to-end instrument to process the cells without human intervention to enhance cell processing uniformity and to maintain the integrity of the cell culture.

Abstract: Improved methods for large scale production of proteins and/or polypeptides in cell culture is provided. In accordance with the present invention, the method provides for culturing cells that have metabolically shifted. The use of such a method or system allows high levels of protein or polypeptide production and reduces accumulation of unwanted metabolic waste such as lactate. Proteins and polypeptides expressed in accordance with the present invention may be advantageously used in the preparation of pharmaceutical, immunogenic, or other commercial biologic compositions, such as antibodies.

Abstract: Provided are a method for establishing a lentiviral vector system capable of directly reflecting type I interferon response, and applications thereof. The method for establishing the lentiviral vector system comprises: cutting a Gaussia luciferase at the position of amino acid 109, removing 16 amino acids from N-terminus, and cloning the two polypeptides into a lentiviral vector to form a lentiviral BiLC expression vector; and cloning a shuttle plasmid of pEntry-IRF3 or pEntry-IRF5 or pEntry-IRF7 by homologous recombination into the lentiviral BiLC expression vector, so as to construct a lentiviral vector IRF3-BiLC or IRF5-BiLC or IRF7-BiLC capable of directly reflecting type I interferon response.