Abstract: The present invention provides compositions and methods for the treatment or prevention of a neurological disease or disorder of the central nervous system (e.g., a storage disorder, lysosomal storage disorder, neurodegenerative disease, etc.) by reconstitution of brain myeloid cell and microglia upon transplantation of hematopoietic cells enriched in microglia reconstitution potential. The invention also provides compositions and methods for ablating and reconstituting microglia.

Abstract: The present disclosure provides compositions and methods for enhanced expression of exogenous genes in eukaryotic cells. The method involves introducing into a mammalian cell an exogenous nucleic acid. wherein the exogenous nucleic acid intearates into a locus of the genome that comprises an extended methylation-free CpG island. Also provided are chromosomal loci, sequences for enhanced and stable expression of exogenous genes.

Abstract: The invention relates to retrieving or modifying target nucleic acids, such as host cell chromosomal DNA, by homologous recombination with vectors that have been cut to provide recombinogenic nucleic acid strands in situ. In some aspects, a marker sequence is created by the method of the invention, wherein the marker sequence is in the product of the method but not present in the starting nucleic acid strands of the method.

Abstract: The present disclosure relates to the composition of one or more agents, therapies, treatments, and methods of use of the agents and/or therapies and/or treatments for upregulating production of lactoferrin or a sub-peptide of lactoferrin. Embodiments of the present disclosure can be used as a therapy or a treatment of adhesions or scarring.

Abstract: Disclosed are adeno-associated viral vectors and plasmids encoding the same. Also disclosed are methods of using adeno-associated viral vectors to deliver a protein of interest to the subject. The disclosed vectors have phenotypes including but not limited to increased retention in the blood of a subject, avoidance of the liver, and transduction of the brain and other tissues.

Abstract: Provided herein are compositions, methods, and devices for the treatment and prevention of atrial fibrillation (AF) using gene therapy techniques. In particular, oxidative stress (OS) and parasympathetic nervous system signaling are inhibited to prevent and/or reverse the electrical remodeling that underlies AF.

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: Nucleic acid-guided nuclease editing in mammalian cells may include passaging mammalian cells, in an automated closed cell editing instrument, into smaller aggregates when the aggregates exceed 50-300 microns in size. A library of viral particles may be delivered to the mammalian cells at a multiplicity of infection such that each mammalian cell receives one or no viral particle. The library may include viral vectors with an editing cassette including a pair of gRNA coding sequence and donor DNA. Conditions may be provided to allow a viral vector of the viral vectors to integrate into the mammalian cells. Enriching for mammalian cells may be done with an integrated viral vector. A nucleic acid-guided nuclease or nuclease fusion or a coding sequence for a nucleic acid-guided nuclease or nuclease fusion may be delivered to the enriched mammalian cells and conditions may be provided to allow editing in the mammalian cells.

Abstract: Provided herein are methods and compositions for treating an eye disorder, for example cone-rod dystrophy type 6 (CORD6). In certain aspects, a therapeutically effective amount of a composition comprising nucleic acids is administered to a subject to treat an autosomal dominant disorder or condition, such as a condition associated with a dominant mutation in a guanylate cyclase 2D (GUCY2D) gene, such as knocking out a dominant mutant form of the gene in the subject. Further provided herein are recombinant AAV particles that comprise one or more recombinant AAV genomes comprising nucleic acids that encode a guide RNA that targets a GUCY2D gene and/or an RNA-guided endonuclease.

Abstract: The present disclosure provides an isolated recombinant oncolytic adenovirus, a pharmaceutical composition, and uses thereof for drugs for treatment of tumors and/or cancers. The recombinant oncolytic adenovirus is a selectively replicating oncolytic adenovirus, and the genome of the recombinant oncolytic adenovirus is integrated with a coding sequence of exogenous shRNA capable of inhibiting PDL1 expression in tumor cells. The replication capability of the virus in normal primary cells is much lower than the replication capability of the virus in tumor cells. Moreover, the expressed shPDL1 can significantly reduce the level of PDL1 protein highly expressed in tumor cells. Thus, the oncolytic killing effect of the oncolytic virus and the anti-tumor immunostimulatory effect of immune cells produce a synergistic effect.

Abstract: The present invention relates to Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in severe, early-onset axonal neuropathy for p.Arg364Trp Mfn2 mutation in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized with multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type at 7, 40, and 48 weeks showed reduced density of myelinated axons and active axonal degeneration in distal but not proximal nerves, as well as axonal degeneration in the fasciculus gracilis of the cervical spinal cord at 40 and 48 weeks not present in 7-week-old cohort Mfn2 mutants, or wild type at 7 or 40 weeks. The p.His361Tyr Mfn2 mutation using CRISPR/Cas9 showed abnormalities in gait dynamics at 8 weeks and lengthening of gait cycle at 16 weeks. The invention provides progressive axonal neuropathy for examining pathogenesis and treatment of CMT2A.

Abstract: The present disclosure provides variant light-responsive polypeptides, and nucleic acids comprising nucleotide sequences encoding the light-responsive polypeptides. The present disclosure provides methods, devices, and systems for controlling the activity of a cell expressing a variant light-responsive polypeptide of the present disclosure.

Abstract: Methods and compositions are provided for treatment of peroxisomal biogenesis disorders (PBDs). More particularly, recombinant adeno-associated viruses (rAAV) provided in the form of compositions are used to deliver a nucleic acid encoding human PEX1 to host cells. The rAAVs comprise a AAV capsid, and packaged therein a vector genome comprising an AAV 5? inverted terminal repeat (ITR) sequence; a promoter; a coding sequence encoding a human PEX1; and an AAV 3? ITR.

Abstract: The present disclosure relates to one or more agents, therapies, treatments, and methods of use of the agents and/or therapies and/or treatments for increasing production of a belatacept-similar protein and interfering RNA of tumor necrosis factor alpha. Embodiments of the present disclosure can be used as a therapy or a treatment for a subject that has a condition whereby the subject's immune system is, or is likely to become, dysregulated and where the production of the belatacept-similar protein and decreased production of tumor necrosis factor alpha may be of therapeutic benefit.

Abstract: Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

Abstract: The invention provides methods and compositions for inducing brown fat cell differentiation through modulation of both Prdm16 and C/EBP? activity and/or expression. Also provided are methods for preventing or treating obesity or an obesity related disorder in a subject through stimulation of both Prdm16 and C/EBP? expression and/or activity. Further provided are methods for identifying compounds that are capable of modulating both Prdm16 and C/EBP? expression and/or activity.

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 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 present disclosure provides an iPSC cell derived from a somatic cell comprising a Cbx family gene and the applications thereof. Also provided are methods for generating the somatic cells that have potential to become induced pluripotent stem (iPS) cells (iPS cells) without oncogenic properties, and methods for generating iPS cells from the population of cells, which may then be used for transplantation and for cellular differentiation and interaction.

Abstract: A method of treating neurodegenerative diseases or disorders, especially Parkinson's disease and a method of inducing neural stem cells from peripheral blood mononuclear cells. The induced neural stem cells can express neural stem cell-related genes and differentiate into neurons, astrocytes and oligodendrocytes. The dopaminergic precursors derived from the induced neural stem cells are transplanted into the striatum of the PD mouse models without any sign of tumorigenesis, thereby improving the behaviors of the PD mouse models and slowing down the progression of Parkinson's disease.

Abstract: A method for acquiring and producing high-purity renal progenitor cells from a renal progenitor cell population into which pluripotent stem cells are induced to differentiate, by identifying a cell surface antigen marker specific to renal progenitor cells. The high-purity renal progenitor cells can be used in regenerative medicine for renal diseases, such as renal failure.