The present disclosure relates to a method of obtaining a cell where fucosylation pathways are modified, leading to production of partially fucosylated and non-fucosylated protein products, specifically antibodies from the cell. The present disclosure employs the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. The method of the present disclosure targets the Fut8 gene and GMD gene in a cell. Such products are used in developing therapeutics and biomarkers, and in diagnosis and prognosis of diseases.

The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

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.

The present invention provides compositions, systems, kits, and methods for generating expression of one or more proteins and/or biologically active nucleic acid molecules in a subject (e.g., at therapeutic levels for extended periods required to produce therapeutic effects). In certain embodiments, systems and kits are provided that comprise a first composition comprising a first amount of polycationic structures, and a second composition comprising a therapeutically effective amount of expression vectors (e.g., non-viral expression vectors not associated with liposomes) that are CpG-free or CpG-reduced, where the expression vectors comprise a first nucleic acid sequence encoding: i) a first therapeutic protein or proteins, and/or ii) a first biologically active nucleic acid molecule or molecules.

Presented herein are techniques to deliver therapeutic substances to a fluidically-sealed chamber within the body of a recipient without compromising the tissue barrier. More specifically, a genetic treatment material is introduced proximate to a tissue barrier, such as the blood-labyrinth barrier, in a recipient. The cells of the tissue barrier are electroporated via implanted electrodes to transfer a least a portion of the genetic treatment material into the cells of the tissue barrier.

The application describes methods and compositions comprising ceDNA vectors useful for the expression of antibodies and antigen-binding fragments thereof in a cell, tissue or subject, and methods of treatment and/or prevention of various diseases, disorders and cancers.

A method for reducing or substantially preventing soft tissue calcification is provided. The method includes administering at least one of a downregulator of at least one plasmin inhibitors and plasmin(ogen) to a subject in need thereof, wherein the at least one plasmin inhibitor includes alpha2-antiplasmin. Further disclosed is a method comprises administering the compound subsequent to muscle injury, and the method further comprising administering an antifibrinolytic.

The present invention provides an mRNA cancer vaccine encoding human GM-CSF fused to multiple tandem epitopes. pVec-GM-CSF-hTes encoding human GM-CSF fused to three tandem hTERT epitopes, pVec-GMKE encoding human GM-CSF fused to three tandem epitopes respectively from MUC1, Kras and EGFR, pVec-hIL-12 encoding human interleukin-12 are respectively constructed, and used as templates for generating the corresponding in vitro transcribed mRNAs, which are mixed together as an mRNA cancer vaccine. This mRNA cancer vaccine contains human GM-CSF used as an immune adjuvant, multiple tandem epitopes constituting as multi-epitope cancer antigens and hIL-12 used to enhance the immunotherapeutic effects.

The present invention provides compositions, systems, kits, and methods for generating expression of one or more proteins and/or biologically active nucleic acid molecules in a subject (e.g., at therapeutic levels for extended periods required to produce therapeutic effects). In certain embodiments, systems and kits are provided that comprise a first composition comprising a first amount of polycationic structures, and a second composition comprising a therapeutically effective amount of expression vectors (e.g., non-viral expression vectors not associated with liposomes) that are CpG-free or CpG-reduced, where the expression vectors comprise a first nucleic acid sequence encoding: i) a first therapeutic protein or proteins, and/or ii) a first biologically active nucleic acid molecule or molecules.

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.