Abstract: The present invention relates to RNA interference-based methods for inhibiting the expression of the myotilin gene. Recombinant adeno-associated viruses of the invention deliver DNAs encoding microRNAs that knock down the expression of myotilin. The methods have application in the treatment of muscular dystrophies such as Limb Girdle Muscular Dystrophy Type 1A.
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.
Type:
Application
Filed:
January 15, 2021
Publication date:
July 29, 2021
Applicant:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
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.
Type:
Application
Filed:
January 28, 2021
Publication date:
July 8, 2021
Applicant:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
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.
Type:
Grant
Filed:
August 7, 2015
Date of Patent:
July 6, 2021
Assignees:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL, THE UNIVERSITY OF WESTERN AUSTRALIA
Inventors:
Kevin Flanigan, Nicolas Wein, Stephen Wilton
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.
Type:
Grant
Filed:
July 3, 2019
Date of Patent:
June 22, 2021
Assignees:
NATIONWIDE CHILDREN'S HOSPITAL, OHIO STATE INNOVATION FOUNDATION
Inventors:
Brian K. Kaspar, Arthur Burghes, Paul Porensky
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.
Type:
Application
Filed:
June 28, 2019
Publication date:
May 13, 2021
Applicant:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Inventors:
Steven David Goodman, Lauren Opremcak Bakaletz
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.
Type:
Application
Filed:
March 14, 2018
Publication date:
May 13, 2021
Applicant:
Research Institute at Nationwide Children's Hospital
Inventors:
Steven David GOODMAN, Lauren O. BAKALETZ
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.
Type:
Grant
Filed:
September 16, 2016
Date of Patent:
April 20, 2021
Assignee:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Abstract: Modified capsid proteins, isolated polynucleotides, methods for the preparation of modified capsid proteins, recombinant viral particles, recombinant expression systems for the generation of modified viral particles, and methods of gene editing and regulation are provided herein.
Type:
Application
Filed:
March 14, 2019
Publication date:
March 25, 2021
Applicant:
Research Intitute at Nationwide Children's Hospital
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.
Type:
Grant
Filed:
August 12, 2016
Date of Patent:
March 16, 2021
Assignees:
Research Institute at Nationwide Children's Hospital, The University of South Florida
Inventors:
Mark Edward Peeples, Michael Nan-hao Teng, Octavio Ramilo, Maria Asuncion Mejias, Emilio Flano
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.
Type:
Grant
Filed:
August 1, 2016
Date of Patent:
March 9, 2021
Assignee:
Research Institute at Nationwide Children's Hospital
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.
Type:
Grant
Filed:
November 5, 2015
Date of Patent:
February 2, 2021
Assignee:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Abstract: A method for generating a electro spun fiber medical implant including determining dimensions of a portion of anatomy of a patient corresponding to the electro spun fiber medical implant via medical imaging, generating a model of the portion of the anatomy based on the dimensions, the model including one or more solid areas and one or more void areas encompassed within the one or more solid areas, inverting the model to generate a mandrel model, the mandrel model generated based on the one or more void areas, generating the mandrel based on the mandrel model, the mandrel including at least one electrically conductive material therein, and applying an electro-spinning process to the mandrel to generate the electro spun fiber medical implant which circumscribes the mandrel, wherein the mandrel is removable from within the electro spun fiber medical implant after a disassembly process.
Type:
Grant
Filed:
August 26, 2016
Date of Patent:
January 19, 2021
Assignees:
CHILDREN'S NATIONAL MEDICAL CENTER, RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL, NANOFIBER SOLUTIONS LLC
Inventors:
Axel Krieger, Narutoshi Hibino, Jed Johnson, Justin Opfermann, Carolyn Cochenour Dorgan, Christopher K. Breuer
Abstract: The disclosure relates to methods for treating subjects with musculoskeletal diseases or with muscle wasting not associated with a musculoskeletal disease by gene transfer with recombinant adeno-associated viruses (rAAV) encoding myostatin inhibitors such as follistatin-344. The rAAV are administered prior to development of diffuse muscle fibrosis in a subject, or the rAAV administration avoids regions of muscle fibrosis in a subject.
Type:
Grant
Filed:
October 9, 2015
Date of Patent:
November 24, 2020
Assignee:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Inventors:
Jerry R. Mendell, Brian K. Kaspar, Samiah Al-Zaidy
Abstract: The disclosure relates to gene therapy vectors, such as AAV vectors, comprising a polynucleotide encoding ?-sarcoglycan (SGCG) and methods of using such gene therapy vectors to treat subjects suffering from a muscular dystrophy, e.g. limb girdle dystrophy type 2C (LGMD2C).
Type:
Application
Filed:
January 30, 2019
Publication date:
November 19, 2020
Applicant:
Research Institute at Nationwide Children's Hospital
Abstract: A cryopreservation instrument and method of using is provided. The instrument includes a substantially planar elongated member comprising a cryosafe material. The elongated member has a first end and a second end. The first end comprises a cap insert dimensioned and configured to be fit in the interior recess of a vial cap, the second end comprises a biological contact portion configured to accommodate biological material.
Type:
Grant
Filed:
September 2, 2015
Date of Patent:
November 17, 2020
Assignee:
Research Institute at Nationwide Children's Hospital
Abstract: The present invention relates to RNA-based methods for inhibiting the expression of the superoxide dismutase 1 (SOD-1) gene. Recombinant adeno-associated viruses of the invention deliver DNAs encoding RNAs that knock down the expression of SOD-1. The methods have application in the treatment of amyotrophic lateral sclerosis.
Type:
Grant
Filed:
July 20, 2018
Date of Patent:
October 6, 2020
Assignees:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL, LUDWIG INSTITUTE FOR CANCER RESEARCH
Inventors:
Brian K. Kaspar, Kevin Foust, Don W. Cleveland
Abstract: Embodiments disclosed herein provide compositions, methods, and uses for respiratory syncytial viruses (RSV) and immunogenic compositions thereof. Certain embodiments provide RSV having cleavage-resistant mutated attachment (G) glycoproteins. In some embodiments, the cleavage-resistant G protein mutants increase production of live attenuated RSV in host cells. Also provided are methods for amplifying RSV in host cells, wherein the amplified RSV has full length G protein. In certain embodiments, the amplified RSV having full length G protein is formulated into immunogenic compositions, including vaccines. Other embodiments provide methods for inducing an effective immune response against RSV infection in a subject.
Type:
Grant
Filed:
June 17, 2016
Date of Patent:
September 1, 2020
Assignee:
The Research Institute at Nationwide Children's Hospital
Inventors:
Mark Edward Peeples, Steven A. Kwilas, Jacqueline Dianne Corry
Abstract: This disclosure provides pharmaceutical compositions and purified or isolated naturally occurring exosome products that have therapeutic use for treating an unmet medical need. The exosome compositions contain an effective amount of exosomes isolated from a body fluid of a non-diseased subject. The compositions are useful in the treatment of a variety of fibrotic diseases.
Type:
Application
Filed:
February 18, 2020
Publication date:
August 20, 2020
Applicant:
Research Institute at Nationwide Children's Hospital