Abstract: The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding an immunomodulatory polypeptide (e.g., a pro-inflammatory cytokine such as a human IL-2 or IL-12 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of cancer, such as lung cancer); and articles of manufacture or kits thereof.

Abstract: A synthetic lentiviral vector construct comprises a genomic RNA packaging enhancer (GRPE) element and lentiviral nucleic acid sequences sufficient for reverse transcription and packaging in a host cell.

Abstract: The present disclosure relates to a method of in vitro engineering of nucleic acids. This disclosure further relates to in vitro engineering of viral genomes and to the improvement of viral properties by in vitro genomic engineering of viral genomes. Specifically, the disclosure relates to in vitro viral genomic digestion using RNA-guided Cas9, the assembly of a recombinant genome by the insertion of a DNA or RNA fragment into the digested viral genome and transformation of a host cell with the recombinant genome. This method also related to in vitro engineering for error correction of nucleic acids.

Abstract: Disclosed herein are engineered light-sensitive proteins, for example channelrhodopsins and variants thereof. Also disclosed are compositions for expressing the light-sensitive proteins in cells, tissues, organs and subjects, and methods for using the light-sensitive proteins to, for example, enable minimally-invasive neuronal circuit interrogation in living organism, and treat neuronal and ocular disorders.

Abstract: Provided herein are conformation-specific antibodies which bind to protein aggregates, such as amyloid fibrils, including aggregates of glucagon and liraglutide. Also provided are methods of using the antibodies to detect protein aggregates in samples, and methods for identifying aggregate-binding antibodies.

Abstract: 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 muscle cells as compared to the infectivity of the muscle 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 muscle cells for the treatment of muscle disorders and diseases.

Abstract: Compositions and methods are provided for treating ocular disorders in a subject are provided. In one aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding CNGA3. In another aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding CNGB3. In another aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding REP-1. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.

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: The present embodiments are directed to methods of using glycine transporter inhibitors, such as GlyT1 inhibitors, or pharmaceutically acceptable salts, solvates or prodrugs thereof, or pharmaceutical compositions thereof, for preventing or treating erythropoietic protoporphyria (EPP), X-linked protoporphyria (XLPP), and/or congenital erythropoietic porphyria (CEP), and related syndromes thereof.

Abstract: 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.

Abstract: The present invention relates to compositions and methods, in particular to methods based on systemic injection of rAAV, for delivering genes to cells of the central nervous system in mammals, such as brain neurons or glial cells, and in particular to motor neurons or glial cells of the spinal cord The invention also relates to methods of treating motor neuron disorders in mammals by expression of therapeutic genes. The invention stems from the unexpected discovery that peripheral injection of AAV vectors leads to a bypass of the blood brain barrier and a massive infection of motor neurons. The invention may be used in any mammal, including human subjects.

Abstract: The present invention relates to adeno-associated viral (AAV) particles encoding siRNA molecules and methods for treating Huntington's Disease (HD).

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: The invention provides methods for treating and diagnosing prostate cancer, as well as related positions and kits.

Abstract: Disclosed are mammalian cells and mammalian cell lines that have a reduced load of remnants of past viral/retroviral infections and methods of producing and using the same.

Abstract: A method for drying moist jellyfish matter is provided. Jellyfish matter undergoes a controlled drying process until the jellyfish matter comprises a dried flake or mass.

Abstract: The present invention provides EpCAM antibodies with different affinities. The present invention also provides chimeric antigen receptors (CARs) specific to EpCAM. CAR T cells comprising human EpCAM scFv having a low and sufficient affinity to EpCAM can avoid targeting healthy tissues with low EpCAM expression while exhibiting long-term efficacy against tumor tissues with high EpCAM expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human EpCAM scFv to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing EpCAM and kill the cancer cells.

Abstract: Provided are a novel fructose-C4-epimerase and a method of producing tagatose using the same.

Abstract: The disclosure herein relates to systems, methods, and devices for medical image analysis, diagnosis, risk stratification, decision making and/or disease tracking. In some embodiments, the systems, devices, and methods described herein are configured to analyze non-invasive medical images of a subject to automatically and/or dynamically identify one or more features, such as plaque and vessels, and/or derive one or more quantified plaque parameters, such as radiodensity, radiodensity composition, volume, radiodensity heterogeneity, geometry, location, and/or the like. In some embodiments, the systems, devices, and methods described herein are further configured to generate one or more assessments of plaque-based diseases from raw medical images using one or more of the identified features and/or quantified parameters.

Abstract: The treatment of bacterial respiratory infections using bacterially-originating antibiotics known as pyocins. In particular, S type pyocins are administered by pulmonary administration for the treatment of such infections.

Abstract: The present invention relates to a method of generating ?? T cells having at least one down-regulated co-inhibitory receptor, the method comprising the steps of: (a) culturing a population of cells comprising ?? T cells with a phosphoantigen to expand the ?? T cells; and (b) culturing the expanded ?? T cells with artificial antigen-presenting cells expressing a Fc receptor, and an anti-CD3 antibody. The present invention also relates to ?? T cells generated according to a method of the present invention, as well as methods of treatment and medical uses thereof.

Abstract: In one aspect, described herein is a recognition element for splicing modifier (REMS) that can be recognized by a compound provided herein. In another aspect, described herein are methods for modulating the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene contains a REMS, and the methods utilizing a compound described herein. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene comprises a REMS, and the methods utilizing a compound described herein. In another aspect, provided herein are artificial gene constructs comprising a REMS, and uses of those artificial gene constructs to modulate functional protein production.

Abstract: The invention provides nucleic acids and nucleic acid expression vectors containing optimized mGluR6 promoters for expression of transgenes in the retina. The compositions and methods of the invention are useful for expression of gene products to preserve, improve, or restore phototransduction or vision.

Abstract: Compositions and methods are provided for treating Leber congenital amaurosis (LCA) in a subject. In one aspect, a recombinant adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding Lebercilin. In another aspect, Lebercilin has an amino acid sequence of SEQ ID NO: 1. In yet another aspect, the nucleic acid molecule has a sequence of SEQ ID NO: 3 or a variant thereof. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.

Abstract: The invention is directed to antibacterial compositions comprising bacteria modified to comprise phasmids engineered to deliver of CRISPR RNAs and methods for their use.

Abstract: Disclosed herein are nucleic acid molecules, polypeptides, cells, vectors, and pharmaceutical compositions relating to miniaturized dystrophin. Methods of production and methods of therapeutic use of the miniaturized dystrophin are also disclosed.

Abstract: Disclosed herein are antibodies or antigen binding fragments thereof that specifically bind human CD8. Also disclosed are fusion proteins comprising a Henipavirus glycoprotein G and CD8 antibodies for targeting and transducing cells expressing CD8. Viral vectors and other compositions containing the fusion proteins, as well as methods of using the fusion proteins, are also disclosed.

Abstract: The present disclosure provides a replication-competent, recombinant oncolytic vaccinia virus; and compositions comprising the replication-competent, recombinant oncolytic vaccinia virus. The present disclosure also provides use of the vaccinia virus or composition for inducing oncolysis in an individual having a tumor.

Abstract: The disclosure provides amino acid sequence variants of Bacillus thuringiensis (Bt) toxins and methods of producing the same. Some aspects of this disclosure provide methods for generating Bt toxin variants by continuous directed evolution. Some aspects of this disclosure provide compositions and methods for pest control using the disclosed variant Bt toxins.

Abstract: Disclosed are methods of administering one or more Bacillus strains to poultry. The Bacillus strains improve bacterial homeostasis in the gastrointestinal tract by inhibiting bacterial pathogens such as E. coli and Clostridium. Administering the Bacillus strains also improves performance such as weight gain and feed conversion. Useful combinations of Bacillus strains and methods of using one or more Bacillus strains are also provided.

Abstract: Microbes can be genetically modified to express biomolecules that are beneficial to mammals and/or to reduce, or eliminate, expression of harmful virulence factors. The growth and viability of such genetically modified microbes can optionally be controlled by inducible promoters that regulate the expression of proteins that are essential to their growth and survival. Compositions comprising such genetically modified microbes as well as methods of making and using the same are disclosed herein.

Abstract: Disclosed herein are peptide sequences capable of directing adeno-associated viruses (AAV) to target specific environments, for example the nervous system and the heart, in a subject. Also disclosed are AAVs having non-naturally occurring capsid proteins comprising the disclosed peptide sequences, and methods of using the AAVs to treat diseases.

Abstract: The present invention provides methods for treating an individual having solid or lymphatic tumor comprising locally administering to the site of the tumor an oncolytic virus, and systemically administering an immunomodulator (including a combination of immunomodulators). The methods may further comprise local administration to the site of the tumor a second immunomodulator (including a combination of immunomodulators). Also provided are compositions and kits for the cancer therapy methods.

Abstract: Provided herein are genetically engineered Vibrio cholerae bacterial strains, compositions including the bacterial strains, and methods of using the same for the prevention of Vibrio cholerae infection in a subject.

Abstract: Described are Neo-Islets comprising: a) dedifferentiated islet cells and mesenchymal and/or adipose stem cells; or b) redifferentiated islet cells and mesenchymal and/or adipose stem cells where the cells have been treated so as to facilitate redifferentiation. Further described herein are methods of generating Neo-Islets, the methods comprising: culturing a) dedifferentiated islet cells and mesenchymal and/or adipose stem cells; or b) redifferentiated islet cells and mesenchymal and/or adipose stem cells; on a surface that promotes the formation of cell clusters. Also described are methods of treating a subject, the methods comprising: providing to the subject Neo-Islets described herein. Additionally described are methods of treating a subject suffering from Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, and other types of insulin-dependent diabetes mellitus, or impaired glucose tolerance by providing to the subject Neo-Islet as described herein.

Abstract: The present invention relates to an animal feed or an animal feed additive comprising Bacillus strains which improve the health and performance of production animals, and the use of such.

Abstract: Provided herein, in some embodiments, are engineered phagemids that comprise at least one synthetic genetic circuit, wherein the at least one synthetic genetic circuit comprises gene sequences encoding at least one non-lytic antimicrobial peptides (AMPs) and/or antibacterial toxin proteins, a stable origin of replication, and a bacteriophage-packaging signal, wherein the engineered phagemid does not comprise some or all gene sequences encoding bacteriophage proteins required for assembly of a bacteriophage particle.

Abstract: The invention relates to methods of modulating immune cells in a patient by altering microbiota of the patient. The invention also relates to methods of modulating treatments or therapies in a subject organism by altering microbiota of the subject. The invention also relates to cell populations, systems, arrays, cells, RNA, kits and other means for effecting this. In an example, advantageously selective targeting of a particular species in a human gut microbiota using guided nucleic acid modification is carried out to effect the alteration.

Abstract: Provided are a fructose-4-epimerase variant having tagatose conversion activity, and a method of producing tagatose using the same.

Abstract: Described herein are constructs used for liver-specific expression of a transgene.

Abstract: The disclosure provides an apparatus and methods for performing a piotomy on a mammal comprising: performing a craniotomy to remove the skull and expose dura mater; removing the dura mater and arachnoid mater to expose subarachnoid space; and performing a piotomy using a laser to create a hole and expose the cerebral cortex.

Abstract: The present invention generally relates to methods of eliciting an immune response in a porcine species subject. In particular, an immunomodulator composition is used to induce an immune response to enhance the subject's ability to fight infectious pathogens.

Abstract: An obligate oHSV vector comprising modified viral DNA genome is provided. A recombinant oHSV-1 construct comprising the obligate oHSV vector and a heterologous nucleic acid sequence encoding an immunostimulatory and/or immunotherapeutic agent is also provided. Compositions comprising the recombinant oHSV-1 construct can be used for treating cancers.

Abstract: The present invention relates to AAVs encoding a SOD1 targeting polynucleotide which may be used to treat amyotrophic lateral sclerosis (ALS) and/or canine degenerative myelopathy (DM).

Abstract: The present invention relates to vectors containing liver-specific regulatory sequences and codon-optimized factor IX or factor VIII genes, methods employing these vectors and uses of these vectors. Expression cassettes and vectors containing these liver-specific regulatory elements and codon-optimized factor IX or factor VIII genes are also disclosed. The present invention is particularly useful for applications using gene therapy, in particular for the treatment of hemophilia A and B.

Abstract: Provided are an siRNA for inhibiting expression of a Hepatitis B virus gene, and a pharmaceutical composition and conjugate containing the siRNA. Each nucleotide in the siRNA is an independently modified or unmodified nucleotide; the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A; the length of the nucleotide sequence A is the same as that of a nucleotide sequence as shown in SEQ ID NO: 1, and the number of the nucleotide differences is not more than three; the antisense strand comprises a nucleotide sequence B; and the length of the nucleotide sequence B is the same as that of a nucleotide sequence as shown in SEQ ID NO: 2, and number of nucleotide differences is not more than three.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.

Abstract: Disclosed are recombinant host cells comprising a promoter-effective nucleic acid molecule operably coupled to a nucleic acid molecule that encodes a plant effector protein or polypeptide that induces an active plant response including, among others, growth enhancement, disease resistance, pest or insect resistance, and stress resistance. Use of these recombinant host cells for modulating plant biochemical signaling, imparting disease resistance to plants, enhancing plant growth, imparting tolerance to biotic stress, imparting tolerance and resistance to abiotic stress, imparting desiccation resistance to cuttings removed from ornamental plants, imparting post-harvest disease or post-harvest desiccation resistance to a fruit or vegetable, or enhancing the longevity of fruit or vegetable ripeness are also disclosed.

Abstract: This disclosure provides methods and compositions for treating lysosomal storage diseases in a subject. In one aspect of the invention, a transgene product is delivered to a subject by administering a recombinant neurotrophic viral vector containing the transgene to the brain. The viral vector delivers the transgene to a region of the brain which is susceptible to infection by the virus and which expresses the encoded recombinant viral gene product. Also provided are compositions for delivery of a transgene product to a subject by administering a recombinant neurotrophic viral vector containing the transgene to the subject's brain. The transgene product may be any that is deficient in a lysosomal storage disease.