Abstract: This disclosure provides methods and compositions for treating lysosomal storage diseases in a subject. In one aspect of the invention, a transgene product is delivered to a subject 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 by administering a recombinant neurotrophic viral vector containing the transgene to the subject's brain. The transgene product may be any that is deficient in a lysosomal storage disease.

Abstract: Without limitation, a method for preventing and/or treating neuropathic pain in a subject/patient comprising administering a therapeutically effective amount of exosomes derived and isolated from mammalian cells to the subject/patient and a method of treating cancer in a subject/patient in need thereof, comprises administering a combination comprising a therapeutically effective amount of exosomes derived and isolated from mammalian cells and a chemotherapeutic agent.

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: Described herein are compositions and methods related to use of exosomes, including cardiosphere derived cell (CDC)-derived exosomes for treatment and prevention of heart related disease and conditions, such as ventral arrhythmias, such as tachycardias. CDC-derived exosomes delivered by endocardial injection can diminish the total amount of isolated late potentials associated with an isthmus of slow conduction, while reducing the isoelectric interval between late abnormal ventricular activity and decreasing the incidence of inducible ventricular arrhythmias, thereby providing a biological treatment for arrhythmias which otherwise requires therapeutic interventions with adverse effects.

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: Truncated junctophilin-2 related proteins, transcriptional repressor domains, vectors encoding the proteins or domains, and methods of using the proteins and domains, are provided.

Abstract: The invention relates to a new, more potent, coagulation Factor IX (FIX) expression cassette for gene therapy of Haemophilia B (HB). Disclosed is a vector for expressing factor IX protein, the vector comprising a promoter, a nucleotide sequence encoding for a functional factor IX protein, and an intron sequence, wherein the intron sequence is positioned between exon 1 and exon 2 of the nucleotide sequence encoding for a functional factor IX protein, and wherein the intron sequence has at least 80% identity to the sequence of SEQ ID NO. 1 as disclosed herein.

Abstract: RNA virus vectors comprising a gene encoding the DNA-dependent activator of interferon-regulatory factors (DAI) protein, and optionally further comprising a gene encoding the receptor-interacting serine/threonine-protein kinase 3 (RIPK3) may be used therapeutically to induce cell death, as well as an inflammatory immune response, against tumors and virally-infected cells.

Abstract: The present invention provides an expression system for a eukaryotic host, which comprises 1) an expression cassette comprising a core promoter, the core promoter controlling the expression of a DNA sequence encoding a synthetic transcription factor (sTF), and 2) one or more expression cassettes each comprising a DNA sequence encoding a desired product operably linked to a synthetic promoter, the synthetic promoter comprising a core promoter, and sTF-specific binding sites upstream of the core promoter. The present invention also provides a method for identifying universal core promoters for eukaryotic hosts, expression systems using universal core promoters, hosts comprising the systems, and methods for producing protein products in eukaryotic hosts.

Abstract: Non-human animals, methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanized programmed death-ligand 1 (PD-L1, PDL1, or B7-H1). Such non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous PD-L1 gene so that the non-human animals express a humanized PD-L1 protein that includes a human portion and an endogenous portion (e.g., a non-human portion).

Abstract: The present invention relates to Adeno-associated virus type 9 methods and materials useful for intrathecal delivery of polynucleotides. Use of the methods and materials is indicated, for example, for treatment of lower motor neuron diseases such as SMA and ALS as well as Pompe disease and lysosomal storage disorders. It is disclosed that administration of a non-ionic, low-osmolar contrast agent, together with a rAA9 vector for the expression of Survival Motor Neuron protein, improves the survival of SMN mutant mice as compared to the administration of the expression vector alone.

Abstract: The invention provides methods of reducing or decreasing a size of a tumor or eliminating a tumor by inhibiting, decreasing, or reducing neo-vascularization or angiogenesis in a tumor in a patient by administering an adenovirus comprising a nucleic acid construct comprising a FAS-chimera gene operably linked to an endothelial cell-specific promoter. Also provided is a homogeneous population of an adenovirus comprising a FAS-chimera gene operably linked to an endothelial cell-specific promoter and its uses thereof.

Abstract: Methods are provided for altering target DNA in a cell genetically modified to express a Cas 9 enzyme that forms a co-localization complex with a guide RNA complementary to the target DNA and that cleaves the target DNA in a site specific manner. Methods include introducing into the cell a first foreign nucleic acid encoding a donor nucleic acid sequence, introducing into the cell from media surrounding the cell the guide RNA complementary to the target DNA and which guides the Cas 9 enzyme to the target DNA, wherein the RNA and the enzyme are members of a co-localization complex for the target DNA, wherein the donor nucleic acid sequence is expressed, wherein the guide RNA and the Cas 9 enzyme co-localize to the target DNA, the Cas 9 enzyme cleaves the target DNA and the donor nucleic acid is inserted into the target DNA to produce altered DNA in the cell.

Abstract: The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising the antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in the methods.

Abstract: The present invention relates to humanisation of antibodies in vivo. The invention provides non-human vertebrates, cells, populations and methods useful for humanising chimaeric antibodies in vivo. Using the present invention it is possible straightforwardly and rapidly to obtain antigen-specific antibodies that are fully human (ie, comprising human variable and constant regions) and have undergone recombination, junctional diversification, affinity maturation and isotype switching in vivo in a non-human vertebrate system. Furthermore, such antibodies are humanised (eg, totally human)—and selected—totally in vivo, and as such the present invention harnesses in vivo filtering for expressibility, affinity and biophysical characteristics in the context of the desired human variable and constant region pairings. This is avoids problems of down-grading antibody characteristics when humanising the constant region of chimaeric antibodies in vitro.

Abstract: Methods for improving the functionality and/or fertility of sperm, for example, by enhancing motility and/or extending the lifespan of sperm by subjecting the isolated sperm to a starvation protocol and/or ionophore are provided. Such methods may be used in, for example, artificial insemination to reduce the number of sperm needed for insemination and to improve conception rates.

Abstract: The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) programmed cell death protein 1 (PD-1), and methods of use thereof. In one aspect, the animals have an insertion of a sequence encoding a human or humanized programmed cell death protein 1 (PD-1) at an endogenous PD-1 gene locus. This animal model can express a PD-1 protein containing a functional domain of the human PD-1 protein, and can be used as an animal model for developing therapeutics for human diseases and disorders, and assessing the toxicity and/or the efficacy of these human therapeutics.

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: Methods are disclosed for reprogramming a somatic cell, including an adherent cell and a cell in suspension, into an induced pluripotent stem comprising expressing exogenous Sox-2, exogenous Klf-4, exogenous Oct3/4 from DNA that has not integrated into the genome of the somatic cell, suppressing p53 activity within the somatic cell, and exposing the somatic cell to reprogramming-assistance factors comprising an exogenous Alk-5 inhibitor, an exogenous histone deacetylase inhibitor, and an exogenous activator of glycolysis. Compositions and kits for use in such methods are also disclosed as are cells made by such a method.

Abstract: The present invention provides a method of treating a disorder using a fibromodulin (FMOD) reprogrammed (FReP) cell. The method comprises administering locally to a human being the FReP cell to a site in need thereof of the human being.