Abstract: Use of an agent which upregulates an activity or amount of miRNA-9 or miRNA-9* is disclosed for the preparation of a medicament for the treatment of a motor neuron disease (MND).

Abstract: A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses human immunoglobulin light chain variable domains derived from a limited repertoire of human immunoglobulin light chain variable gene segments that comprise histidine modifications in their germline sequence. Methods of making non-human animals that express antibodies comprising histidine residues encoded by histidine codons introduced into immunoglobulin light chain nucleotide sequences are provided.

Abstract: A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses a single light chain variable domain derived from a single rearranged light chain variable region gene in the germline of the non-human animal, wherein the single rearranged light chain variable region gene comprises a substitution of at least one non-histidine encoding codon with a histidine encoding codon. Methods of making non-human animals that express antibodies comprising a histidine-containing universal light chain are provided.

Abstract: A method for intracellular delivery of isolated naked nucleic acids into a biological tissue or organ, that includes (a) contacting the tissue or organ with an efficient amount of at least one active corticosteroid, and (b) contacting the tissue or organ treated in step b with an efficient amount of isolated naked nucleic acids, wherein step (a) is carried out for a period of time ranging from at least five minutes to at most two hours and being immediately followed by step (b).

Abstract: An excellent nucleic acid delivery composition is provided which has reduced cytotoxicity and improved nucleic acid introduction efficiency and gene expression efficiency. The composition comprises: a block copolymer having an uncharged hydrophilic polymer segment and a cationic polymer segment; a cationic polymer; and a nucleic acid, wherein the mol percentage (B/H ratio) of the cationic groups of the block copolymer to the total cationic groups of the block copolymer and the cationic polymer is between 25% and 90%.

Abstract: The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.

Abstract: The present invention concerns the endonucleases capable of cleaving a target sequence located in a “safe harbor loci”, i.e. a loci allowing safe expression of a transgene. The present invention further concerns the use of such endonucleases for inserting transgenes into a cell, tissue or individual.

Abstract: Described herein are novel biological circuit chemotactic converter that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for detecting and converting external inputs, such as chemoattractants, into outputs that allow for autonomous chemotaxis in cellular systems. Flexibility in these biological circuit chemotactic converter is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create network systems that regulate chemotactic responses based on the combination and nature of input signals received.

Abstract: The present invention provides new sequences, gene constructions, vectors and pharmaceutical compositions for the treatment of diseases and specially, for the treatment of mucopolysaccharidoses.

Abstract: The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.

Abstract: Methods are provided for using field-derived colonies of insects that comprise field-evolved resistance to insecticidal toxins that are produced in transgenic plants. The methods find use in resistance management strategies for transgenic crop plants expressing insecticidal toxins.

Abstract: The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.

Abstract: Devices, compositions, and methods are described which provide a tubular nanostructure targeted to a lipid bilayer membrane. The targeted tubular nanostructure can have a surface region configured to pass through a lipid bilayer membrane of a cell, a hydrophobic surface region flanked by two hydrophilic surface regions configured to form a pore in a lipid bilayer membrane of a cellular organelle, and at least one ligand configured to bind one or more cognates on the lipid bilayer membrane of the cellular organelle. The target cell can be, for example, a tumor cell, an infected cell, or a diseased cell in a subject. The tubular nanostructure can form a pore in the lipid bilayer membrane of the cellular organelle, e.g., mitochondria, which can permit transit or translocation of at least one compound across the membrane and cause cell death of the target cell.

Abstract: Described are methods and compositions for increasing islet-1 (Isl1) activity (e.g., biological activity) and or expression (e.g., transcription and/or translation) in a biological cell and or in a subject.

Abstract: The present disclosure provides a method of generating an induced pluripotent stem cell; as well as nucleic acids and genetically modified host cells useful in generating iPSCs. The present disclosure provides iPSCs, and methods of use of same.

Abstract: This disclosure relates to the discovery and isolation of the entire cluster of genes encoding R-type high molecular weight bacteriocins that specifically kill Clostridium difficile bacteria, dangerous pathogens. Also disclosed are methods of producing the R-type bacteriocins in innocuous aerobic producer cells. Disclosed also are small, non-ORF1374 receptor binding domains (RBDs), which are incorporated into diffocins to form engineered or variant diffocins having altered killing spectra. Variant diffocins provided herein may include a heterologous RBD and its cognate base plate attachment region (BPAR), or a fused BPAR. This invention offers a potent bactericidal agent with increased thermal and pH stability, and methods for producing it, in order to kill selectively C. difficile bacteria in the environment of the gastrointestinal tract where they can cause great harm and even death of the infected patient or farm animal.

Abstract: A linker for a unimolecular FRET biosensor based on a principle of fluorescence resonance energy transfer, the linker including: a polypeptide containing 52 to 400 amino acids residues, wherein at least 45% of a total number of the amino acid residues are glycine, alanine, or both thereof, and at least 10% of the total number of the amino acid residues are alanine.

Abstract: The invention in some aspects relates to recombinant adeno-associated viruses useful for targeting transgenes to CNS tissue, and compositions comprising the same, and methods of use thereof. In some aspects, the invention provides methods and compositions for treating CNS-related disorders.

Abstract: The invention relates to a modular transport platform (MTP) configured to penetrate a target cell, deliver the MTP into the target cell, provide a pH dependent membrane disruption activity, direct intracellular transport into a target subcellular compartment of the target cell, and couple the active agent within the modular platform. The modular transport platform includes: (1) a ligand module to target a specific receptor on the surface of the target cell; (2) an endosomolytic module that provides pH-dependent membrane disruption activity within the target cell; (3) an intracellular transport module to cause delivery of the MTP to a particular subcellular compartment; (4) a module for intracellular retention; (5) a module for subcellular recognition; (6) a substance to be transported by the MTP; and (7) a carrier module for unifying the modules and coupling the modules with the transported substance.

Abstract: Provided herein are methods for cell therapy by modifying transfused cells to express an inducible caspase 9 protein, so that the cells may be selectively killed if the patient experiences dangerous side effects. Provided also within relates in part to methods for preventing or treating Graft versus Host Disease by modifying T cells before administration to a patient, so that they may be selectively killed if GvHD develops in the patient.