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: The invention is directed to a chimeric antigen receptor (CAR) directed against CD19, which comprises an amino acid sequence of any one of SEQ ID NO: 1-SEQ ID NO: 13. The invention also provides T-cells expressing the CAR and methods for destroying malignant B-cells.

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

Abstract: The present disclosure provides a synthetic nanoparticle comprising a peptide nucleic acid (PNA) oligomer conjugated to a lipid, wherein the PNA oligomer noncovalently complexes with an immunomodulatory compound, thereby forming a nanoparticle. The nanoparticles are useful to elicit immune responses and can be used to treat a broad range of cancers and infectious diseases.

Abstract: Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain targeted to HER2, a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

Abstract: The invention provides methods of inducing or improving responsiveness to a VEGF antagonist to a subject or a subject population comprising administering an adenovirus comprising a nucleic acid construct comprising a F AS-chimera gene operably linked to an endothelial cell-specific promoter and administering the VEGF antagonist.

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: A transposon (TnC_T7) was developed to partially supply the transcriptional machinery during functional analysis of genomic/metagenomic libraries. This transposon was conceived and constructed to have the ability to integrate randomly into any episomal DNA, allowing the inducible expression of the adjacent DNA regions in both directions. In general, this genetic tool included a kanamycin resistance gene, two bidirectional T7 promoters and the T7RNA polymerase-coding gene, the latter under the regulation of the inducible arabinose promoter (PBAD). The experimental validation confirmed the TnC_T7 potential to be used in functional genomic/metagenomic studies, in order to partially overcome the limitations of the bacterial hosts, which prevent them to recognize most of foreign genes from DNA libraries.

Abstract: The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor under the control of an inducible promoter. In some alternatives the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain under the control of a drug inducible promoter. Controlling the expression of the chimeric receptor provides for the ability to turn expression on and off depending on the status of the patient.

Abstract: A composition comprising at least one AAV vector formulated for intrathecal delivery to the central nervous system is described. The composition comprises at least one expression cassette which contains sequences encoding an immunoglobulin construct linked to expression control sequences therefor and a pharmaceutically acceptable carrier. The immunoglobulin construct may be an immunoglobulin modified to have decreased or no measurable affinity for neonatal Fc receptor (FcRn).

Abstract: Disclosed herein are methods and compositions for treating or preventing Huntington's Disease.

Abstract: They are provided gene constructs comprising a nucleotide sequence encoding the Insulin-like growth factor 1 (IGF-1) of a mammal; and target sequences of a microRNA of a tissue where the expression of IGF-1 is wanted to be prevented, wherein the sequences (a) and (b) are operationally linked to a promoter of ubiquitous expression. Also provided are expression vectors comprising the gene construct and pharmaceutical compositions comprising them. They are useful in the treatment and/or prevention of diabetes mellitus in mammals, wherein a dysfunction and/or a loss of the beta-cells of the islets of Langerhans is present.

Abstract: The present invention relates to a recombinant adeno-associated viral (r AAV) vector comprising neuropeptide Y (NPY) coding sequence and neuropeptide Y2 receptor (NPY2R) coding sequence. The invention further relates to a AAV particle comprising said vector, wherein the vector is encapsulated by adeno-associated virus (AAV) capsid proteins. Also, a pharmaceutical composition comprising said AAV particle, for use in the prevention or treatment of a neurological disorder in mammals, such as epilepsy.

Abstract: The present disclosure relates to an efficient genome editing technique. In one aspect, the technique can greatly improve the efficiency of homologous recombination during intracellular targeting, including gene targeting. Using this technique, genetically modified cell lines, rat, mouse, zebrafish, and fertilized eggs of other species can be quickly and efficiently generated.

Abstract: Compositions and implants for articular cartilage repair or regeneration are described. The compositions are hydrogel-based compositions that can incorporate signaling molecules for cartilage repair. The compositions include microcapsules having predetermined erosion profiles that are loaded with nanogels having predetermined sustained release profiles for signaling molecules conjugated to the nanogels. A plurality of compositions, each carrying different signaling molecules, can be layered to form a multi-layered implant, with each layer sequentially releasing the encapsulated signaling molecules over a predetermined period of time. The compositions can carry additional components to encourage tissue generation such as stem cells and extracellular matrix (ECM) components.

Abstract: The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.

Abstract: The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 300 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in rod photoreceptors of a gene when operatively linked to a nucleic acid sequence coding for said gene.

Abstract: Disclosed are novel gene therapy constructs containing both HEXA and HEXB genes to treat GM2 gangliosidoses, including Sandhoff disease and Tay-Sach's disease. Also described are co-treatments using chaperone and anti-inflammatory agents to enhance the effects of gene therapy.