Abstract: The present invention relates generally to polypeptides or nucleic acids for use in the treatment, management, retardation of progression or normalisation of development of an iduronate-2-sulfatase (IDS) deficiency and/or Mucopolysaccharidosis type II (MPS II) in an individual, wherein the polypeptides comprise iduronate-2-sulfatase (IDS) tethered to a tandem repeat of Apolipoprotein E (ApoEII) or the nucleic acids comprise an iduronate-2-sulfatase (IDS) gene sequence tethered to a tandem repeat of the Apolipoprotein E (ApoEII) gene sequence. The invention also relates to haematopoietic stem and progenitor cells (HSPCs) transduced by such nucleic acids for use in therapies.

Abstract: A method of preparing a chimeric virus comprising bocavirus capsid protein (VP) and a recombinant adeno-associated (AAV) viral genome, and isolated mutant bocavirus genomes, are provided.

Abstract: Provided are improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. Also provided are improved gene therapy methods for treating hematopoietic-related disorders. Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

Abstract: The present invention relates to a stable method for introducing at least one inducible cassette into a cell, and permitting controllable transcription from within that inducible cassette. The method may be used for any cell type, from any eukaryotic organism, but has a particular application in the introduction of inducible cassettes into pluripotent stem cells, such as animal or human pluripotent stem cells (hPSCs). The inducible cassette is controllably inserted in such a way to ensure that the genetic material it contains is not silenced or subject to negative influences from the insertion site, and transcription of the genetic material is controlled.

Abstract: The invention relates to an artificial nucleic acid molecule comprising at least one open reading frame and at least one 3?-untranslated region element (3?-UTR element) comprising a nucleic acid sequence which is derived from the 3?-UTR of a FIG4 gene or from a variant of the 3?-UTR of a FIG4 gene. The invention further relates to the use of such an artificial nucleic acid molecule in gene therapy and/or genetic vaccination. Furthermore, the invention relates to the use of a 3?-UTR element comprising a nucleic acid sequence which is derived from the 3?-UTR of a FIG4 gene or from a variant of the 3?-UTR of a FIG4 gene for the stabilization and/or prolongation of protein expression from a nucleic acid sequence comprising such 3?-UTR element.

Abstract: This invention is directed to, inter alia, stable cartilage-derived progenitor cell lines as well as methods for producing stable cartilage-derived progenitor cell lines from diseased human cartilaginous tissues and lesions. Also provided herein are methods for using cartilage-derived progenitor cell lines for treatment of cartilage and bone degenerative diseases.

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 Programmed cell death 1 (Pdcd1) gene. The non-human animals, in some embodiments, comprise a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).

Abstract: The present invention relates to a cryopreserved in vitro cell culture comprising human pancreatic progenitor cells that co-express pancreatic-duodenal homeobox factor-1 (PDX1) and NK6 homeobox 1 (NKX6.1) and are chromogranin negative. The present invention also relates to a method for cryopreserving an in vitro population of human pancreatic progenitor cells that co-express PDX1 and NKX6.1 and are chromogranin negative.

Abstract: The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

Abstract: The present disclosure provides infectious recombinant adeno-associated virus (rAAV) virions that comprise a variant capsid protein and a heterologous nucleic acid. The present disclosure further provides the variant adeno-associated virus (AAV) capsid proteins (and/or a nucleic acid encoding the variant AAV capsid proteins), which confer to an infectious rAAV virion an increased resistance to human AAV neutralizing antibodies. The present disclosure further provides host cells comprising an infectious rAAV virion and/or a nucleic acid encoding a subject variant AAV capsid protein. The present disclosure further provides methods of delivering a heterologous nucleic acid to a target cell where the target cell is contacted with a subject infectious rAAV virion. The present disclosure further provides methods of delivering a gene product to an individual, the methods generally involving administering an effective amount of a subject rAAV virion to an individual in need thereof.

Abstract: The invention relates to methods, kits and compositions for reducing the level of or eliminating Bacteroides in situ. The invention encompasses methods of preventing myocarditis, treating myocarditis or dilated cardiomyopathy, or limiting progression of myocarditis toward dilated cardiomyopathy in a subject in need thereof, comprising reducing the amount of Bacteroides sp. in the subject. The invention further encompasses methods of diagnosis of a subject as having myocarditis or dilated cardiomyopathy. The invention also encompasses compositions preventing myocarditis, treating myocarditis or dilated cardiomyopathy, or limiting progression of myocarditis toward dilated cardiomyopathy in a subject in need thereof.

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: 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 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: 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.