Abstract: The application relates to a chimeric antigen receptor that directly and/or indirectly targets cells and their uses in tumor immunotherapy. The application also relates to polynucleotides that encode the chimeric antigen receptor and optionally accessory genes, vectors, and host cells comprising the chimeric antigen receptor and optionally a second antigen targeting moiety (e.g., a second chimeric antigen receptor or a bispecific molecule). The application also relates to methods for preparing host cells comprising the chimeric antigen receptor and optionally the second antigen targeting moiety.

Abstract: There is provided a nucleic acid molecule comprising a nucleotide sequence encoding a Factor VIII protein, wherein a B domain portion of the Factor VIII protein is encoded by a nucleotide sequence between 90 and 111 nucleotides in length and has an amino acid sequence that is at least 85% identical to SEQ ID NO: 4 which comprises six asparagine residues. Also provided is a Factor VIII protein, a vector comprising the above nucleic acid molecule, a host cell, a transgenic animal, a method of treating Haemophilia for example, Haemophilia A, and a method for the preparation of a parvoviral gene delivery vector.

Abstract: Methods and compositions using a nucleic acid molecule encoding an atonal-associated factor in combination with a co-transcription factor and/or inhibitor of a gene silencing complex to change the sensory perception of an animal are described.

Abstract: The present disclosure provides methods of generating multiplexed genetically modified animals, for example, porcine endogenous retrovirus (PERV)-inactivated pigs. The disclosure also provides methods of improving the birth rate of multiplexed genetically modified animals. In some embodiments, the present closure is concerned with the generation and utilization of porcine cells in which porcine endogenous retroviral (PERV) elements have been inactivated. In sonic embodiments, the PERV-free or PERV-reduced porcine cells are cloned to produce porcine embryos. In some embodiments, the PERV-free or PERV-reduced embryos may be grown into adult swine from which organs and/or tissues may be extracted and used for such purposes as xenotransplantation into non-porcine animals such as humans.

Abstract: The present application provides methods of enhancing T cell function (e.g., expansion, persistence and/or effector functions), particularly by genetic modification of the Regnase-1, Batf, and additional genes (alone or in combination). The application also provides modified T cells manufactured using the methods provided by this invention and related pharmaceutical compositions. The application further provides methods of using the modified T cells for treating a disease (e.g., a cancer or an infectious disease).

Abstract: The application provides modified immune effector cells wherein the DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mediated de novo DNA methylation of the cell genome is inhibited, and STAT5 signaling pathway is activated. The application also provides related pharmaceutical compositions and the methods for generating such modified immune effector cells. The application further provides uses of such modified immune effector cells for treating diseases such as cancers, infectious diseases and autoimmune diseases.

Abstract: A nucleic acid construct and mammalian cell harboring nucleic acids encoding an anti-CD7 chimeric antigen receptor are provided. Methods for treating cancer, in particular a hematologic cancer, using the nucleic acid construct or mammalian cell are also described.

Abstract: The invention relates to a high-throughput method for characterizing the genome-wide activity of editing nucleases in vitro.

Abstract: The present disclosure provides chimeric antigen receptors (CARs), particularly CARs that have enhanced antitumor properties and/or can be regulated by safety switches. Also provided are polypeptides of the CARs and other related molecules, polynucleotides, vectors, and cell compositions comprising the same. Pharmaceutical compositions comprising the polypeptides, polynucleotides, vectors, or cells of the present disclosure, and their uses in treating a cancer in a subject are also provided.

Abstract: Methods and compositions using a nucleic acid molecule encoding an atonal-associated factor in combination with a co-transcription factor and/or inhibitor of a gene silencing complex to change the sensory perception of an animal are described.

Abstract: Provided herein are methods and compositions for determining T-cell differentiation by comparing the methylation status of T cells relative to a T cell methylation index and using this determination to identify or isolate populations of T cells having desired T cell multipotency. Further, the present methods and compositions can be used to monitor or treat symptoms of chronic infections, autoimmune diseases, and cancer.

Abstract: Methods for removing excess free ?-globin in erythroid cells and treating a thalassemia using an agent that activates Unc-51 Like autophagy activating Kinase (ULK) are described.

Abstract: Compositions and methods are provided for modifying and treating neuroinflammatory and neurodegenerative diseases. The methods and compositions can be used to ameliorate the effects of a deficiency in the LC3-associated endocytosis (LANDO) pathway for clearing ?-amyloid. Thus, methods are further provided for modulating ?-amyloid clearance using an effective amount of a pharmaceutical composition that targets the LANDO pathway. Accordingly, pharmaceutical compositions that target the LANDO pathway are provided herein. The methods and compositions described herein can be used to treat neuroinflammatory and neurodegenerative diseases, such as Alzheimer's disease.

Abstract: The invention is directed to methods of assessing the safety of therapeutic compounds and therapeutic genetic manipulations, including integrating gene therapy vectors and genome editing. In particular, the invention provides a method, wherein the oncogenic potential of therapeutic compounds and therapeutic genetic manipulations, including integrating gene therapy vectors and genome editing, is determined by determining the percentage of differentiation blocked hematopoietic progenitor cells.

Abstract: A method of identifying a lead or candidate compound that modulates the activity of GTPase-Activating Protein SH3 Domain-Binding Proteins (G3BP) is provided, which includes determining whether a compound modulates the interaction between the N-terminal Nuclear Transport Factor 2-like (NTF2L) domain of G3BP and FGDF peptide of ubiquitin specific protease 10 (USP10) or non-structural protein 3 (nsP3).

Abstract: In some aspects, provided herein are methods and compositions for treating or preventing adverse cardiac events in a patient who has suffered an invasive pneumococcal infection or is at risk of such an infection. The compositions include fusion proteins comprising a CbpA polypeptide or active fragment or variant thereof and optionally a T cell epitope (TCE) and a third immunogenic polypeptide from a bacteria.

Abstract: The present invention relates to nucleic acid molecules containing spacers and methods of using the same.

Abstract: Compositions and methods are provided for modifying the expression or activity of CXorf67 in order to reduce the activity of PRC2. Increased expression of CXorf67 was identified in certain cancers, including PFA ependymomas. Thus, provided herein are methods for reducing PRC2 activity in order to treat cancer. The methods and compositions can be used to treat symptoms cancer or to screen for compounds useful in decreasing PRC2 activity and treating cancer. Further provided are methods of identifying subjects at an increased risk of developing cancer by measuring the expression or activity of CXorf67 or the mutation of specific sites within CXorf67.

Abstract: Compositions and methods are provided for suppressing tumors by modulating the LAP pathway. Targeting components of the LAP pathway for specific drug design can be used as n immunotherapy strategy that modulates the tumor microenvironment. It is well established that infiltrating monocytes and macrophages play a pivotal role in shaping an immunosuppressive tumor microenvironment. By modulating LAP in the innate immune cells, the function of effector T cells can be manipulated toward an effective, cytotoxic immune response that can eliminate tumor cells. Thus, methods are provided for reducing the size or number of tumor cells and for treating cancer or other cell proliferative disorders. Further provided are methods for increasing the Th1 response or increasing IFN? and/or TNF? expression in the tumor microenvironment by administering a LAP inhibitor.

Abstract: In one aspect, the invention relates to substituted 1-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1-mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.