Abstract: The present invention relates to recombinant adeno-associated virus (rAAV) delivery of polynucleotides for treating Duchenne Muscular Dystrophy resulting from the duplication of DMD exon 2. The invention provides rAAV products and methods of using the rAAV in the treatment of Duchenne Muscular Dystrophy.

Abstract: This disclosure provides methods for determining whether a subject is suffering from a liver cancer, such as hepatic carcinoma, comprising determining the expression level of miRNA-33b and/or miRNA46-a, in a sample of exosomes enriched from a body fluid of the subject, wherein low expression of the miRNA-33b and/or miRNA-46a as compared to a control is indicative of the subject suffering from a liver cancer, e.g., hepatic carcinoma. The subject may also be suffering from a fibrotic disease, liver fibrosis, and/or is or was infected with hepatitis B.

Abstract: The present disclosure provides a novel method for monitoring the conversion of oral precancerous lesions to oral cancers, including monitoring changes in oral exosome concentrations in a subject, thereby determining the state of the disease and the risk of carcinogenesis. The disclosure also relates to a detection kit for use in the above method.

Abstract: Disclosed are approaches to determining a sensitivity of a bacterium to a given antibiotic and generating targeted treatments based on the sensitivity. One or more antibiotics may be selected for a chronic/recurrent infection resulting from a biofilm so as to reduce dose and or length of course of antibiotic treatment. For example, if a bacterial pathogen is determined to be sensitive to an antibiotic in its planktonic form but resistant to that antibiotic in its biofilm form, then the biofilm may be dispersed or disrupted from the biofilm residence in order to clear the infection. In various embodiments, a dispersal or disruption method and/or agent may be determined based at least in part on a rate of bacterial release from a biofilm that sensitizes the pathogen to a chosen antibiotic.

Abstract: The present invention relates to methods for shifting the splicing profile of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding U7-based small nuclear RNAs to induce DUX4 exon-skipping and the expression of shortened forms of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

Abstract: This disclosure provides kits and methods for determining whether a subject is suffering from a liver disease, and/or whether the subject will be a responsive to a therapy for a liver disease. The disclosed methods comprise determining the miR profile of exosomes isolated from a body fluid of the subject.

Abstract: Provided herein are derivatives of HMGB1 that have been engineered to possess the same efficacious anti-bio film activity but are smaller and do not induce inflammation.

Abstract: Provided herein are methods to inhibit or disrupt a bio film comprising contacting the bio film with an agent that cleaves the Holliday junction (HJ) structure in the bio film.

Abstract: Provided herein are recombinant AAV vectors encoding a GALT protein. Also provided in this disclosure are compositions and methods for the treatment of galactosemia.

Abstract: Provided herein are prenatal methods comprising administering an effective amount of a biocompatible microsphere comprising a biofilm-generating probiotic bacterium, a prebiotic, and/or a prebiofilmic.

Abstract: Provided herein are methods and compositions for disrupting biofilms in vitro and in vivo. Also disclosed are antibodies comprising a specified heavy chain (HC) immunoglobulin variable domain sequence and/or a specified light chain (LC) immunoglobulin variable domain sequence.

Abstract: This disclosure provides isolated or recombinant polypeptides that are useful to vaccinate individuals suffering from chronic/recurrent biofilm disease or as a therapeutic for those with an existing infection. The individual's immune system will then naturally generate antibodies which prevent or clear these bacteria from the host by interfering with the construction and or maintenance of a functional protective biofilm. Alternatively, antibodies to the polypeptides can be administered to treat or prevent infection. Bacteria that are released from the biofilm by our technology are more readily cleared by the remainder of the host's immune system.

Abstract: Provided herein are methods and compositions for disrupting biofilms in vitro and in vivo. Also disclosed are antibodies comprising a specified heavy chain (HC) immunoglobulin variable domain sequence and/or a specified light chain (LC) immunoglobulin variable domain sequence.

Abstract: The present invention relates to the delivery of oligomers for treating patients with a 5? mutation in their DMD gene other than a DMD exon 2 duplication. The invention provides methods and materials for activating an internal ribosome entry site in exon 5 of the DMD gene resulting in translation of a functional truncated isoform of dystrophin. The methods and materials can be used for the treatment of muscular dystrophies arising from 5? mutations in the DMD gene such as Duchenne Muscular Dystrophy or Becker Muscular Dystrophy.

Abstract: The disclosure relates to methods for inhibiting the stability of a biofilm comprising contacting the biofilm with an effective amount of an agent that interferes with the binding of a polyamine to DNA in the biofilm. Also provided herein are methods for treating a biofilm in a subject comprising administering to the subject infected with a biofilm an effective amount of an agent that interferes with the binding of a polyamine to the DNA in the biofilm. Further described herein are methods for treating a biofilm in a patient suffering from systemic lupus erythematosus (SLE) and/or cystic fibrosis (CF) comprising administering an effective amount of an agent that interferes with the conversion of B-DNA to Z-DNA in the biofilm or its local environment.

Abstract: Methods of breaking down a biofilm or inhibiting, preventing or treating a microbial infection that produces a biofilm are disclosed, which involves administration of a polypeptide that has one or more modified HMG-box 1 domains to a subject suffering from the infection or having the biofilm. By competing with microbial proteins that bind to DNA scaffold in the biofilm, these polypeptides destabilize the biofilm leading to destruction and removal of the biofilm by the immune system.

Abstract: The present disclosure relates to recombinant adeno-associated virus (rAAV) delivery of a GALGT2 polynucleotide. The disclosure provides rAAV and methods of using the rAAV for GALGT2 gene therapy of neuromuscular disorders. Exemplary neuromuscular disorders include, but are not limited to, muscular dystrophies such as Duchenne muscular dystrophy, Congenital Muscular Dystrophy 1A and Limb Girdle Muscular Dystrophy 2D.

Abstract: Embodiments disclosed herein provide compositions, methods, and uses for respiratory syncytial viruses (RSV) and immunogenic compositions thereof. Certain embodiments provide RSV having a mutated NS1 protein, where the mutation causes the uncoupling of the NS1 protein's replication and type I interferon (IFN) antagonist functions. In some embodiments, this uncoupling can produce virions capable of inducing a strong, long-lasting innate immune response while maintaining its ability to replicate in vitro. Also provided are methods for amplifying RSV in host cells, wherein amplified RSV has mutated NS1 protein in which the protein's replication and IFN antagonistic functions are uncoupled. In certain embodiments, the amplified RSV having mutated NS1 protein is formulated into immunogenic compositions, including vaccines. Other embodiments provide methods for inducing an effective immune response against RSV infection in a subject.

Abstract: This disclosure provides isolated or recombinant polypeptides that are useful to vaccinate individuals suffering from chronic/recurrent biofilm disease or as a therapeutic for those with an existing infection. The individual's immune system will then naturally generate antibodies which prevent or clear these bacteria from the host by interfering with the construction and or maintenance of a functional protective biofilm. Alternatively, antibodies to the polypeptides can be administered to treat or prevent infection. Bacteria that are released from the biofilm by our technology are more readily cleared by the remainder of the host's immune system.

Abstract: The present invention is directed to methods and materials for producing recombinant viruses. In particular, methods and materials are provided for producing recombinant viruses in eukaryotic microalgae such as Chlamydomonas reinhardtii. Recombinant adeno-associated viruses are examples of recombinant viruses produced according to the invention.