Chimeric antigen receptors containing CD33 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.

Disclosed are methods of treating a subject, such as those having or at risk of cardiomyopathies, with an effective amount of a recombinant adeno-associated virus (rAAV) virion, the rAAV virion comprising an AAV capsid and an expression cassette comprising a polynucleotide encoding a DWORF polypeptide operatively linked to a promoter. Compositions and kits relating to the same are also disclosed.

A vibration monitoring system includes a plurality of encoders and an analyzer. The encoders are configured to generate multiple pulse train signals for multiple wheels. Each encoder is coupled to a respective one of the multiple wheels and generates a single one of the pulse train signals. The analyzer is coupled to the encoders and is configured to generate multiple pulse per revolution signals and multiple angular velocity signals for the wheels in response to the pulse train signals. Each pulse per revolution signal conveys a single pulse per rotation of the respective wheel. The analyzer is further configured to generate an input phasor array representative of the pulse per revolution signals, generate a response phasor array in response to the angular velocity signals for the wheels, and generate a report that identifies at least one vibrating wheel in response to the input phasor array and the response phasor array.

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 cells of the retina for the treatment of retinal disorders and diseases.

Provided are methods and compositions for treating cancer in a subject in need thereof. One of the top gene products in glioblastoma multiforme (GBM) is KLRB1 (also known as CD161), a C-type lectin protein that binds to CLEC2D. Binding of CLEC2D to the KLRB1 receptor inhibits the cytotoxic function of NK cells as well as cytokine secretion. KLRB1 is only expressed by small subpopulations of human blood T cells, and consequently little is known about the function of this receptor in T cells. However, preliminary data demonstrate that KLRB1 expression is induced in T cells within the GBM microenvironment. In an exemplary embodiment, a method is provided comprising administering an agent capable of blocking the interaction of KLRB1 with its ligand. The agent may comprise an antibody or fragment thereof, which may bind KLRB1 or CLEC2D.

The present invention relates to a pharmaceutical composition for preventing or treating peripheral vascular disease, the composition comprising, as an active ingredient: (a) hepatocyte growth factor (HGF) or an isoform thereof, and stromal cell derived factor 1α (SDF-1α); or (b) a polynucleotide encoding the HGF and a polynucleotide encoding the SDF-1α. The peripheral vascular disease (for example, ischemic limb disease) can be more effectively prevented or treated through the significant promotion of vascular endothelial cell migration and angiogenesis in the case of singly using the composition of the present invention than in the case of using HGF, an isoform thereof, SDF-1α or a polynucleotide codes a protein thereof.

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

Disclosed are compositions for delivering gene editing molecules to a cell. Exemplary compositions comprise a micelle assembled from a plurality of triblock copolymers, wherein each triblock copolymer having at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block, wherein: the at least one poly(L-histidine) block complexes with the at least one gene editing molecule; and the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule.

Methods and compositions are provided for activating transcription in a mammalian cell.

A method for treating a patient suffering from a neuronal hypo-kinetic disease or a neuronal hyper-kinetic disease by modulating neuronal activity in the: internal globus pallidus (GPi), in the anterior motor thalamus and/or in the external globus pallidum (GPe) and/or in the subthalamic nucleus (STN) by utilizing suppressor and/or enhancer DREADDs is provided.