Abstract: 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.

Abstract: The present disclosure relates to a preparation of CD140a/PDGFR? positive cells that comprises oligodendrocyte progenitor cells co-expressing OLIG2 and CD140a/PDGFR?. The preparation of cells is derived from pluripotent cells that were derived from skin cells, fibroblasts, umbilical cord blood, peripheral blood, bone marrow, or other somatic cells. The cell preparation has an in vivo myelination efficiency that is equal to or greater than the in vivo myelination efficiency of a preparation of A2B5+/PSA-NCAM? sorted fetal human tissue derived oligodendrocyte progenitor cells. Methods of making, isolating and using the disclosed cell preparation are also described.

Abstract: The present disclosure relates to recombinant adeno-associated virus (rAAV) delivery of a GALGT2 polynucleotide. The disclosure provides rAAV and methods of using the rAAV for GALGT2 gene therapy of neuromuscular disorders. Exemplary neuromuscular disorders include, but are not limited to, muscular dystrophies such as Duchenne muscular dystrophy, Congenital Muscular Dystrophy 1A and Limb Girdle Muscular Dystrophy 2D.

Abstract: The invention relates to synthetic liver-specific promoters and expression constructs for producing polypeptides and functional nucleic acids in the liver of a subject. The invention further relates to Factor VIII proteins containing modifications in the amino acid sequence of the Factor VIII protein, as well as nucleic acid constructs encoding the Factor VIII proteins and methods of using these compositions to treat a bleeding disorder.

Abstract: A method for producing eyefield progenitor cells, including: (a) obtaining a starting population comprising human pluripotent stem cells (hPSCs) that are dissociated to essentially single cells; (b) culturing said hPSCs to a contact-inhibited monolayer; (c) contacting said hPSC monolayer in a primary differentiation medium to generate a homogeneous, contact-inhibited monolayer of anterior neuroectodermal cells (ANECs); (d) dissociating said homogeneous ANECs from (c) into essentially single cells; (e) forming dissociated ANECs into size-controlled and homogeneous 3D aggregates (ANEBs), wherein the ANEBs are 3D aggregates of anterior neuroectodermal cells that are distinct from embryoid bodies; and (f) culturing said ANEBs in a primary differentiation medium in suspension to further differentiate them to Eyefield Progenitor Cells (EFPCs).

Abstract: The disclosure provides a non-human transgenic animal having at least one CREBBP gene locus into which a mutation has been introduced, wherein the mutated CREBBP gene encodes a mutant CREBBP consisting of an amino acid sequence having at least 90% identity with the amino acid sequence of SEQ ID NO: 5. The disclosure also provides a method of producing the transgenic animal comprising introducing a mutation into at least one CREBBP gene locus of a non-human animal. The disclosure further provides use of the transgenic animal as a model of Rubinstein-Taybi syndrome or advanced sleep phase syndrome.

Abstract: A novel method of inducing neural progenitor cells, oligodendrocyte progenitor cells, oligodendrocytes from human iPSCs at an unprecedented efficiency and functionality. The core of the invention is the use of experimentally discovered transcription factors at multiple critical differentiation decision points along a pluripotent to ectoderm, neural ectoderm to NPCs to OPCs to oligodendrocytes pathway in a previously unknown manner.

Abstract: Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Lymphocyte activation gene 3 (Lag3). The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Lag3 locus so that the non-human animals express a Lag3 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).

Abstract: The invention relates to chimeric AAV capsids targeted to oligodendrocytes and virus vectors comprising the same. The invention further relates to methods of delivering a nucleic acid of interest to an oligodendrocyte in vitro and in vivo, methods of delivering a nucleic acid of interest to an area of the CNS bordering a compromised blood-brain barrier, and methods of treating disorders associated with oligodendrocyte dysfunction using the AAV capsids and virus vectors of the invention.

Abstract: The present disclosure relates to methods for making genetic edits in vitro in a non-human vertebrate cell or embryo at a plurality of target chromosomal DNA sites. Methods for making a non-human animal having multiplex genetic edits at a plurality of target chromosomal DNA sites and making a non-human vertebrate animal chimeric for host cells and donor cells are also considered.

Abstract: Provided herein are polypeptides comprising one or more non-native cysteine residues that form a disulfide bridge between non-native cysteines within the protein or between non-native cysteines of two monomers of the protein. Such modified human polypeptides are useful in treatment of genetic diseases via enzyme replacement therapy and/or gene therapy.

Abstract: The present invention relates to a contact lens-type dressing manufactured by using a partially cured amniotic membrane dressing and a method of manufacturing same. The method of manufacturing a partially cured contact lens-type amniotic membrane dressing, and the partially cured contact lens-type amniotic membrane dressing of the present invention have a simple manufacturing method, can produce a contact lens-type amniotic membrane without foreign matter, have excellent biocompatibility, have excellent lens compatibility such as transparency and tensile strength compared to a fully cured contact lens-type amniotic membrane dressing, and also have excellent wound healing effects, and therefore, can be effectively used for the treatment of eye diseases such as corneal damage.

Abstract: This application provides: a non-human animal that comprises a mouse artificial chromosome comprising a human antibody heavy chain gene or gene locus, a human antibody light chain ? gene or gene locus, and/or a human antibody light chain ? gene or gene locus, and in which endogenous antibody genes or gene loci corresponding to at least 2 human antibody genes or gene loci have been knocked out, wherein the animal can be stably retained through generations and can produce human antibodies; a method for producing the non-human animal; and a method for producing human antibodies using the non-human animal.

Abstract: A method is provided for simultaneously producing both nephron progenitor cells and ureteric epithelial progenitor cells including the step of contacting intermediate mesoderm cells with: fibroblast growth factor 9 and/or fibroblast growth factor 20 and optionally, one or more selected from the group consisting of: bone morphogenic protein 7; heparin; a Wnt agonist; retinoic acid; and an RA antagonist. The concentrations of Wnt agonist, retinoic acid and/or RA antagonist may be manipulated to favour the relative production of nephron progenitor cells and ureteric epithelial progenitor cells. The intermediate mesoderm cells are ultimately derived from human pluripotent stem cells via a posterior primitive streak stage. The nephron progenitor cells and ureteric epithelial progenitor cells may have end uses such as for kidney repair and regeneration, bioprinting of kidneys and screening compounds for nephrotoxicity.

Abstract: The present invention relates to compositions and methods for treating cancer. More specifically, the present invention relates to compositions of engineered oncolytic viruses for administration to a subject with cancer that specifically lyse tumor cells and actively target tumor cells and cell debris to antigen presenting cells, in order to generate anti-tumor immunity.

Abstract: The present invention provides, among other things, methods and compositions for effective delivery of messenger RNA (mRNA) to the central system (CNS). In particular, the present invention provides methods and compositions for administering intrathecally to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome, such that the administering of the composition results in the intracellular delivery of mRNA in neurons in the brain and/or spinal cord. The present invention is particularly useful for the treatment of CNS diseases, disorders or conditions, such as spinal muscular atrophy.

Abstract: Disclosed are cell membrane-derived nanovesicles, a method of preparing the nanovesicles, and a pharmaceutical composition and a diagnostic kit using the nanovesicles. The cell membrane-derived nanovesicles may prevent potential adverse effects because intracellular materials (e.g., genetic materials and cytosolic proteins) unnecessary for delivering therapeutic or diagnostic substances are removed from the nanovesicles. In addition, as the nanovesicles may be targeted to specific cells or tissues, therapeutic or diagnostic substances may be predominantly delivered to the targeted cells or tissues, while delivery of the substances may be inhibited. Therefore, the nanovesicles may alleviate suffering and inconvenience of patients by reducing adverse effects of therapeutic substances and by improving efficacy of the substances.

Abstract: The present disclosure provides distinct therapeutic populations of cells that form a pharmaceutical composition useful in hematopoietic stem/progenitor cell transplant. For example, the present disclosure provides a therapeutic population of cells, comprising an enriched population of hematopoietic stem/progenitor cells, memory T cells, regulatory T cells, and wherein the population of cells is depleted of naïve conventional ??-T cells. The present disclosure further provides methods of treatment using the therapeutic population of cells. In other embodiments, the present disclosure provides methods of producing a therapeutic population of cells.

Abstract: The present disclosure provides soluble truncated mutant programmed death-ligand 1 (PD-L1) peptides. Polynucleotides and vectors encoding the soluble truncated mutant PD-L1 peptides are also provided. Further, methods of using the soluble truncated mutant peptides to promote differentiation of CD4+ effector T (Th1) cells into Foxp3+ regulatory T (Treg) cells are provided.

Abstract: The present invention relates to a method for obtaining stable pseudotyped lentiviral particles including a heterologous gene of interest, comprising the following steps: a) transfecting at least one plasmid in appropriate cell lines, wherein said at least one plasmid comprises the gene of interest, the rev. gag and pol genes, and a sequence coding for an ERV syncytin, wherein the rev, gag and pol genes are retroviral genes; b) incubating the transfected cells obtained in a), so that they produce the stable pseudotyped lentiviral particles in the supernatant; and c) harvesting and concentrating the stable lentiviral particles obtained in b). The present invention also relates to a method to transduce immune cells using lentiviral vectors pseudotyped with an ERV syncytin glycoprotein. The method can be performed on non-stimulated blood cells or on cells stimulated briefly with IL7, and the cells can be expanded. The stable pseudotyped lentiviral particles obtained are particularly useful in gene therapy.