Provided is a novel vector for immunostimulation and methods of using same in immunotherapy, in particular cancer immunotherapy. The novel vector comprises nucleic acid sequences encoding 4-1BB ligand (4-1BBL, CD137 ligand), single chain IL-12 (sc IL-12) and IL-2, wherein the vector provides for an increased expression of 4-1BBL as compared to the expression levels of sc IL-12 and IL-2. Specifically, the nucleic acid sequences encoding 4-1BBL, sc IL-12 and IL-2 are organized in the vector in 5′ to 3′ orientation in a sequential order 1, 2, 3, with the proviso that the gene encoding sc IL-12 is not at position 1. Embodiments of the present disclosure include virus particles comprising the novel vector as well as cancer or immune cells transduced or transfected with the novel vector.

The described invention provides a method for reducing progression of lung fibrosis after a lung injury comprising administering a therapeutic amount of a therapeutic agent, wherein the therapeutic amount is effective: (a) to modulate expression of a T-box transcription factor in a population of cells in lung; and (b) to reduce proliferation of the population of cells in lung expressing the T-box transcription factor. According to some embodiments the T-box transcription factor is Tbx4.

Provided are methods and compositions for delivering a nucleic acid, protein, and/or ribonucleoprotein payload to a cell. Also provided are delivery molecules that include a peptide targeting ligand conjugated to a protein or nucleic acid payload (e.g., an siRNA molecule), or conjugated to a charged polymer polypeptide domain (e.g., poly-arginine such as 9R or a poly-histidine such as 6H, and the like). The targeting ligand provides for (i) targeted binding to a cell surface protein, and (ii) engagement of a long endosomal recycling pathway. As such, when the targeting ligand engages the intended cell surface protein, the delivery molecule enters the cell (e.g., via endocytosis) but is preferentially directed away from the lysosomal degradation pathway.

Compositions for use in treating subjects with USH2A-associated retinal and/or cochlear degeneration that result from mutations in exon 13 of the USH2A gene by deletion of exon 13 from the USH2A gene or transcripts, and methods of use thereof, as well as genetically modified animals and cells.

Disclosed are methods and pharmaceutical compositions for treating and inhibiting conical vascularization including conical vascularization associated with viral infection, chemical injury, autoimmune conditions, and post-corneal transplantation or in subjects having a PAX6 mutation associated with conical vascularization. The methods and pharmaceutical compositions are utilized in administering treatment that results in increased concentration of FOXC1 in a subject's cornea in order to treat or inhibit corneal vascularization.

Disclosed herein are methods of treating, preventing, or reducing the incidence of an inflammatory disease or disorder and methods of inhibiting, preventing, or reducing the incidence of one or more activities in a cell with an inhibitor of a Motile Sperm Domain containing Protein 2 (MOSPD2). Also disclosed are inhibitors of MOSPD2 and pharmaceutical compositions containing MOSPD2 inhibitors.

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.

A method of treating hyperglycemia, diabetes, metabolic syndrome, insulin resistance (insulin insensitivity), impaired glucose tolerance, high glucose levels, pulmonary hypertension, and/or a condition arising from any of the foregoing in a patient is provided. The method comprises knocking down mARC2 or mARC1 expression in the patient, or otherwise decreasing mARC2 and mARC1 activity in the patient.

The present disclosure relates to: an adipocyte-targeting non-viral gene delivery complex comprising a sh(FABP4+FABP5) dual plasmid vector; and treatment for obesity and obesity-induced metabolic syndromes by using the same and, more particularly, to a gene delivery complex comprising: an adipocyte-targeting sequence; a nine-arginine (R9) peptide; and a dual plasmid vector comprising a gene for treatment of obesity and obesity-induced metabolic syndromes, wherein the gene for treatment of obesity and obesity-induced metabolic syndromes is a base sequence inhibiting the expression of a FABP4 gene and a FABP5 gene. According to the present disclosure, in order to treat obesity-related diseases, a dual plasmid vector capable of simultaneously inhibiting the FABP4 and FABP5 genes is produced, and this vector is bound to a predetermined delivery system that specifically delivers the vector into adipocytes so as to provide a gene delivery complex. In this way, it is possible to achieve an excellent therapeutic effect on obesity which targets only adipocytes without cytotoxicity.

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.