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 muscle cells as compared to the infectivity of the muscle 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 in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more muscle cells for the treatment of muscle disorders and diseases.

Abstract: Provided is a T cell receptor capable of binding to a peptide having the amino acid sequence shown in SEQ ID NO: 27 or a complex of the peptide and HLA-A24. A T cell receptor capable of binding to a peptide having the amino acid sequence shown in SEQ ID NO: 28 or a complex of the peptide and HLA-A02. Disclosed T cell receptors are useful in treating or avoiding cancers which are associated with expression of glypican-3.

Abstract: The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

Abstract: The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

Abstract: The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

Abstract: Provided herein are binding molecules, such as those that recognize or bind a peptide epitope of a cancer antigen, such as expressed on a cancer cell, including cells infected with human papilloma virus (HPV) or that contain HPV DNA sequences and/or those that recognize or bind a peptide epitope of HPV 16 E6 or E7, in the context of a major histocompatibility complex (MHC) molecule. Among the provided binding molecules are T cell receptors (TCRs) or antibodies, including antigen-binding fragments thereof, that bind or recognize such peptide epitopes. The present disclosure further relates to engineered cells comprising such binding molecules, e.g., TCRs or antibodies (and chimeric antigen receptors containing the antibodies), and uses thereof in adoptive cell therapy.

Abstract: The present invention relates to nucleic acid regulatory elements that are able to enhance endothelial cell-specific expression of genes, methods employing these regulatory elements and uses of these elements. Expression cassettes and vectors containing these nucleic acid regulatory elements are also disclosed. The present invention is particularly useful for applications using gene therapy, more particularly endothelial cell-directed gene therapy, and for vaccination purposes.

Abstract: Disclosed herein is a recombinant nucleic acid, comprising: a mitochondrial targeting sequence; a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein; and a 3?UTR nucleic acid sequence. Also disclosed is a pharmaceutical composition comprising the recombinant nucleic acid and a method of treating Leber's hereditary optic neuropathy (LHON) using the pharmaceutical composition.

Abstract: The invention provides novel compositions, methods, and therapeutic uses related to fusogenic protein MINION (microprotein inducer of fusion).

Abstract: The invention provides compositions and methods for the preparation, manufacture and therapeutic use of viral vectors, such as adeno-associated virus (AAV) particles having viral genomes encoding one or more antibodies or antibody fragments or antibody-like polypeptides, for the prevention and/or treatment of diseases and/or disorders.

Abstract: The present invention relates to a combined preparation comprising (i) a modulator of pyruvate kinase M2 (PKM2) activity, and (ii) an agent providing high mobility group box 1 (HMGB1) polypeptide or a derivative thereof. The present invention also relates to the aforesaid combined preparation for use as a medicament and for use in the treatment of inappropriate cellular proliferation, preferably in the treatment of cancer. Moreover, the present invention relates to a method for determining whether a subject suffering from inappropriate cellular proliferation is amenable to a treatment comprising administration of a modulator of PKM2 activity as the only PKM2 inhibitor and to treatment methods related thereto.

Abstract: The invention found that first, the feasibility of transfer of tumor resistance and other healthy longevity characters through transplantation of bone marrow mononuclear cells (BMMNC) or hematopoietic stem cells (HSC)/hematopoietic stem and progenitor cells (HSPC) consisting of genetically engineered EKLF gene encoding the hematopoietic transcription factor EKLF. Secondly, the present invention demonstrates expression of EKLF in the long-term hematopoietic stem cells (LT-HSC), and thus EKLF as a target of regulation of hematopoiesis.

Abstract: Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer. The methods and compositions involve genetically engineered immune cells (e.g., T cells), in which the endogenous CD70 gene is disrupted by genetic editing, for example, the CRISPR/Cas9 gene editing technology.

Abstract: A chimeric antigen receptor (CAR) and a gene encoding the CAR. The CAR comprises an extracellular domain capable of binding to an antigen, a transmembrane domain, and intracellular immune co-stimulatory molecule, wherein the extracellular domain comprises a D2 domain of a Slit2 protein. A chimeric antibody-expressing cell, which introduces a gene encoding the CAR into a cell so as to express the CAR on the surface of the cell. The CAR or CAR-expressing cell can be used as a cell drug for the treatment of tumor diseases. By using the CAR for engineering cells, especially T cells, the engineered T cells can specifically recognize and kill tumors, and have higher tumoricidal activity.

Abstract: Provided are a human PD-1 knockdown siRNA, a recombinant expression CAR-T vector, a preparation method thereof, and an application of the same. A PD-1 knockdown siRNA expression cassette and an siRNA expression product thereof can be applied to a CAR-T therapy of multiple myeloma (MM) for eliminating or alleviating a tumor immune escape mechanism, and in the suppression of an immune escape mechanism in a CAR-T therapy of a tumor, such as pancreatic cancer, brain glioma, and myeloma.

Abstract: Provided is a method of genetically incorporating an L-dihydroxyphenylalanine in a target protein.

Abstract: The invention provides a plasmid comprising two or more anti-obesity genes. Also provided by the invention are compositions and host cells comprising the plasmid and methods of increasing the metabolic activity in a mammal. The invention provides a plasmid comprising two or more of (a) a nucleic acid sequence encoding islet amyloid polypeptide (IAPP), (b) a nucleic acid sequence encoding leptin (LEP), and (c) a nucleic acid sequence encoding fibronectin type III domain containing 5 (FNDC5).

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 muscle cells as compared to the infectivity of the muscle 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 in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more muscle cells for the treatment of muscle disorders and diseases.

Abstract: There is described a new gene therapy approach for treating Wilson's disease in which a nucleic acid molecule is used which comprises a nucleotide sequence encoding for a functional ATP7B protein wherein the nucleotide sequence has at least 85% identity to the sequence of SEQ ID NO: 1. Also described are vectors comprising the nucleotide sequence and methods and uses thereof.

Abstract: The present disclosure provides TCRs with high or enhanced affinity against various tumor associated antigens (including human Wilms tumor protein 1 (WT 1) epitopes and mesothelin epitopes), T cells expressing such high affinity antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress one or more of these antigens, such as in cancer.