Abstract: Chimeric antigen receptors containing CD19/CD20 or CD20/CD19 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Abstract: A method of controlling the number of cells in a population of cells having silenced transcription of a target nucleic acid as a function of time includes recruiting a chromatin regulator (CR) to a site proximal to a transcription initiation site of the target nucleic acid to form a fraction of silenced cells in the population of cells. The chromatin regulator may be EED, KRAB, DNMT3, HDAC4, EZH2, REST, or a combination thereof.

Abstract: Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.

Abstract: The present invention provides a combination therapy of genetically modified vaccinia virus (particularly oncolytic vaccinia virus) and another cancer therapy for use in treating cancer, and a pharmaceutical composition and a combination kit for use in the therapy. More specifically, the invention provides a therapy with vaccinia virus containing a polynucleotide encoding interleukin-7 (IL-7) and a polynucleotide encoding interleukin-12 (IL-12) in combination with an immune checkpoint inhibitor, and a pharmaceutical composition and a combination kit for use in the therapy.

Abstract: Provided are embodiments of replicative oncolytic adenovirus AD5 ApoA1 for inhibiting tumor growth and metastasis and use thereof in preparation of anti-tumor drugs. The virus can rapidly replicate in tumor cells and exert an oncolytic effect. Tumor cells infected with the virus can highly express apolipoprotein ApoA1 which can be secreted extracellularly in large quantities, significantly inhibit the invasion and metastasis of tumor cells, inhibit tumor-promoting inflammation pathways, and significantly reduce a IDO-1 which is a key molecule that leads to tumor immune escape. The virus can significantly inhibit tumor growth, inhibit tumor invasion, delay progression of cachexia and prolong the survival time of tumor-bearing mice in mice with liver cancer, breast cancer, colon cancer, or lung cancer.

Abstract: A person's iris color can lighten, such as from brown to lighter brown, green, hazel, or blue, by introducing a melanocyte-killing agent through the cornea of the person's eye and contacting the anterior surface of the iris with the agent at a dose sufficient to kill melanocytes in the iris stroma.

Abstract: The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

Abstract: Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more ceils of the retina for the treatment of retinal disorders and diseases.

Abstract: Provided are cells containing exogenous antigen and uses thereof.

Abstract: The present invention provides nucleic acids encoding a fusion protein comprising a nucleotide sequence encoding GRIM-19 or a biologically active fragment or derivative thereof and a nucleotide sequence encoding a protein transduction domain. Proteins encoded by the nucleic acids, pharmaceutical compositions and methods of treatment are also provided. The invention also provides viral vectors comprising GRIM-19 or a biologically active fragment or derivative thereof, pharmaceutical compositions and methods of treatment using the same.

Abstract: Provided are cells containing exogenous antigen and uses thereof.

Abstract: Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

Abstract: Disclosed herein are nucleic acid molecules, polypeptides, cells, vectors, and pharmaceutical compositions relating to miniaturized dystrophin. Methods of production and methods of therapeutic use of the miniaturized dystrophin are also disclosed.

Abstract: Disclosed herein are methods and compositions for inactivating TCR and/or HLA genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.

Abstract: Chimeric antigen receptors containing TSLPR-CD19 and TSLPR-CD22 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Abstract: Provided are methods for screening a desired variant of a target gene in a eukaryotic system. Compositions for screening a desired variant of a target gene are also provided.

Abstract: Recombinant cells and methods therefor are contemplated that allow for rapid and high titer production of recombinant viruses, and especially replication deficient Ad5 virus. In some preferred aspects, the host cell is modified to produce an inhibitor that reduces or eliminates the expression of a therapeutic protein encoded in the virus, while in other aspects, the virus includes a gene that directly or indirectly reduces or eliminates the expression of a therapeutic protein encoded in the virus. Most preferably, shRNA encoded by the host cell will reduce or suppress expression of a payload gene encoded in the recombinant virus.

Abstract: The invention provides a bidirectional hCMV-CAG4 promoter and recombinant vectors and recombinant virus comprising the bidirectional hCMV-CAG4 promoter operably linked to a first transgene in one direction and to a second transgene in the opposite direction. The invention also provides methods of making and using such recombinant vectors and recombinant virus.

Abstract: Provided herein are compositions and methods for decreasing tau mRNA and protein expression. These compositions and methods are useful in treating tau-related diseases and disorders.

Abstract: Concentrated, low-viscosity, low-volume liquid pharmaceutical formulations of polysaccharides and nucleic acids have been developed. Such formulations can be rapidly and conveniently administered by subcutaneous or intramuscular injection, rather than by lengthy intravenous infusion. These formulations include low-molecular-weight and/or high-molecular-weight polysaccharides and nucleic acids, and viscosity-lowering agents.