Abstract: Embodiments are directed to methods and compositions for modulating an immune response. In certain aspects the immune response is a type I hypersensitivity response. In particular aspects the subject has allergic asthma or allergic rhinitis. Using a conventional experimental asthma mouse model (BALB/c), the inventors demonstrate that aerosol administration of TLR agonists, in particular a combination of TLR2/6 and TLR9 agonist (e.g., TLR9 oligonucleotide agonist/PAM2CSK4) along with an antigen (e.g., ovalbumin (OVA)) suppresses the immune response as exemplified by the production of antigen-specific IgE and decreases the number of airway eosinophils in bronchoalveolar lavage fluid (BAL) in response to intraperitoneal (IP) immunization with an antigen mixed with alum.

Abstract: The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and/or class II major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and/or CIITA or by using nucleic acid molecules which inhibit the expression of B2M and/or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component. In addition, expression of immunosuppressive polypeptide can be performed on those modified T-cells in order to prolong the survival of these modified T cells in host organism.

Abstract: A therapeutic agent comprising a nucleic acid and a TCR modified immune cell and use thereof. The therapeutic agent comprises a first composition comprising a first active ingredient and a second composition comprising a second active ingredient. The first active ingredient includes or contains a nucleic acid having a labeling polypeptide coding sequence for being introduced into a tumor cell and/or a cancer cell. The labeling polypeptide has one or more epitope polypeptides which can be presented on a surface of the tumor cell and/or cancer cell by MHC class I molecules. The second composition comprises a second active ingredient in a second pharmaceutically acceptable carrier and the second active ingredient comprises a T cell receptor modified immune cell which can specifically recognize and bind to the epitope polypeptide presented by MHC class I molecules. The therapeutic agent achieves synergistic treatment effect and provides a new route for tumor treatment.

Abstract: Embodiments of the invention concern the regeneration of chondrocytes and cartilage-type cells. In certain embodiments, one or more genes are employed for the regeneration of chondrocytes and cartilage-type cells. In particular embodiments, one or more gene therapy regimens are employed for the regeneration of chondrocytes and cartilage-type cells. In particular aspects, embodiments concern cartilage repair, such as articular cartilage repair. More particularly, embodiments for the disclosure concern using gene therapy for the attraction, generation and/or regeneration of chondrocytes or other cartilage-type cells and/or the generation and/or repair of cartilage tissue. In specific embodiments of the disclosure, gene therapy is provided that is capable of attracting and/or generating desired cells in vivo.

Abstract: Compositions and methods of modulating an innate immune response with circular RNAs are disclosed. In particular, the disclosure relates to methods for modifying an RNA by circularization and the use of circular RNAs generated with exogenous introns to stimulate an innate immune response or circular RNAs generated with endogenous introns to prevent immune recognition of foreign RNA.

Abstract: Livestock animals and progeny thereof comprising at least one edited chromosomal sequence that alters expression or activity of a somatostatin receptor (SSTR) protein are provided. Livestock animal cells that contain such edited chromosomal sequences are also provided. The livestock animals have improved growth performance and weight gain. Methods for producing livestock animals with increased growth performance are also provided.

Abstract: A therapeutic agent and method of administering the therapeutic agent for the treatment of tumors and/or cancers of a subject, the therapeutic agent comprising a first pharmaceutical composition comprising a first active ingredient in a first druggable vehicle, wherein the first active ingredient comprises a nucleic acid encoding a labelling polypeptide comprising one or more antigenic epitope peptides and/or encoding a MHC protein; a second pharmaceutical composition comprising a second active ingredient in a second druggable vehicle, wherein the second active ingredient comprises immune cells purified from peripheral blood or from tumor tissue and are cultured in vitro; wherein the nucleic acid when administered to the subject as part of the pharmaceutical composition causes the tumor cells and/or cancer cells of the subject to express the one or more antigenic epitope peptides to elicit an immune response of the immune cells.

Abstract: RNA encoding an immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially neutral surface charge at physiological pH and are effective for immunisation.

Abstract: The invention provides expression vectors, nucleic acids, vector particles and methods of treatment involving these vector particles, comprising an engineered KCNA1 gene encoding an edited Kv1.1 potassium channel, as well as methods of confirming the presence of engineered KCNA1 mRNA in a cell. The features of the engineered KCNA1 gene combine to advantageously enhance the translation and activity of the Kv1.1 protein and improve detection of KCNA1 gene expression in a cell and can be used for example in the treatment of epilepsy and similar neurological disorders.

Abstract: A perfusion plate that can be combined with pillar plates containing cell layers is disclosed. The perfusion plate can have an inflow reservoir and an outflow reservoir connected by at least one channel, which fluidly connects the perfusion wells to the reservoirs for the flow of a fluid such as growth media. A perfusion plate can be part of an assembly containing a pillar plate, a lid, and a transparent bottom for visualizing cell growth in the perfusion wells. The perfusion-pillar plate assembly can facilitate perfusion-based tissue culture and tissue communication for high throughput, high-content, drug screening.

Abstract: Described herein are compositions (e.g. cells and transgenic animals) and methods relating to engineered Ig loci that permit expression of particular antibodies or antibody segments while still permitting recombination and/or maturation process for antibody optimization.

Abstract: RNA encoding an immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially neutral surface charge at physiological pH and are effective for immunisation.

Abstract: Provided herein are, inter alia, methods useful for delivering nucleic acids and kinase inhibitors to a cell. The methods provided herein include the delivery of therapeutic nucleic acids to cancer cells by contacting a cancer cell with a kinase inhibitor and a therapeutic nucleic acid. The methods provided herein are therefore, inter alia, useful for the treatment of cancer.

Abstract: Disclosed herein are an mRNA targeting molecule comprising an N-acetylgalactosamine binding polypeptide and a preparation method therefor. A plasmid vector containing a DNA fragment formed by sequentially connecting a promoter, a target gene, a specific protease cleavage sequence, and a polynucleotide sequence encoding a GBD capable of binding to N-acetylgalactosamine, is transcribed to obtain an mRNA, which is connected to a DNA-puromycin linker under the action of a T4 ligase. The resulting connection product is subjected to protein translation, followed by cleavage using a specific protease to obtain an mRNA-puromycin-GBD complex, which then binds to a GBD protein sequence under the action of an N-acetylgalactosamine transferase to form an mRNA-puromycin-GBD-GalNAc complex, thereby modifying the mRNA with GalNAc, thus achieving the purpose of precise administration in a process of mRNA drug delivery and increasing the efficacy of the mRNA drug molecule.

Abstract: The present invention is directed to methods and compositions comprising novel CRISPR polypeptides and polynucleotides for site-specific cleavage and nicking of nucleic acids, transcriptional control and genome editing.

Abstract: The present invention relates to Adeno-associated virus type 9 methods and materials useful for intrathecal delivery of polynucleotides. Use of the methods and materials is indicated, for example, for treatment of lower motor neuron diseases such as SMA and ALS as well as Pompe disease and lysosomal storage disorders. It is disclosed that administration of a non-ionic, low-osmolar contrast agent, together with a rAAV9 vector for the expression of Survival Motor Neuron protein, improves the survival of SMN mutant mice as compared to the administration of the expression vector alone.

Abstract: RNA encoding an immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially neutral surface charge at physiological pH and are effective for immunisation.

Abstract: There is described a chimeric antigen receptor (CAR) which comprises an antigen binding domain which selectively binds to Receptor Tyrosine Kinase Like Orphan Receptor 1 (ROR1), and its use. Also described is a T cell comprising the CAR and its use in the treatment of cancer.

Abstract: Provided are plasmid vector constructs encoding multiple immunomodulatory proteins where each protein or component thereof can be expressed utilizing appropriate promotors and/or translation modifiers. Additional immunomodulatory proteins and genetic adjuvants containing shared tumor antigens can be added to further therapeutic potential as well as allow tracking of therapeutic treatment. Also provides are methods of expressing the plasmid constructs.

Abstract: RNA encoding an immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially neutral surface charge at physiological pH and are effective for immunisation.