Abstract: The present disclosure provides a variant AAV capsid protein that confers tropism to lung cells and recombinant adeno-associated viruses comprising the variant AAV and pharmaceutical compositions comprising same and their use in the delivery of heterologous nucleic acids to lung cells for the treatment of pulmonary disorders.
Type:
Grant
Filed:
October 6, 2022
Date of Patent:
November 7, 2023
Assignee:
4D Molecular Therapeutics Inc.
Inventors:
Melissa Kotterman, Peter Francis, Melissa Calton, Johnny Gonzales, Roxanne Croze, Christopher Schmitt
Abstract: Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.
Abstract: A method of treating cancerous tumors is presented herein. The method includes injecting an effective dose of a plasmid encoded for IL-12, B7-1 or IL-15 into a cancerous tumor and subsequently administering at least one high voltage, short duration pulse to the tumor. The electroporation pulses may be administered at least 700V/cm for a duration of less than 1 millisecond. The intratumor treatments with electroporation may be administered in at least a two-treatment protocol with the time between treatments being about 7 days. The intratumor treatments with electroporation may be administered in a three-treatment protocol with a time of four days between the first and second treatments and a time of three days between the second and third treatments. It was found that the intratumor treatments using electroporation not only resulted in tumor regression but also induced an immune memory response which prevented the formation of new tumors.
Abstract: The present invention presents a sequence of the AAV/UPR-plus virus, a genetic treatment method and its use in the treatment of neurodegenerative diseases, such as Parkinson's and Huntington's diseases, among others, as presented in the in vitro studies shown in FIG. 14/17.
Abstract: The present invention provides a method for preventing or treating a liver disease selected from the group consisting of non-alcoholic fatty liver, non-alcoholic steatohepatitis and hepatic fibrosis comprising administrating at least one selected from the group consisting of an Ssu72 peptide, a polynucleotide encoding the Ssu72 peptide, and an expression vector comprising the polynucleotide.
Type:
Grant
Filed:
July 25, 2022
Date of Patent:
October 24, 2023
Assignee:
CUROGEN TECHNOLOGY CO., LTD.
Inventors:
Chang Woo Lee, Jin Kwan Lee, Hyun Soo Kim, Ji Hyun Choi, Se Eun Byeon, Hae In Lee, Hyeonju Jo
Abstract: Provided is an anti-mesothelin chimeric antigen receptor specifically binding to mesothelin. The anti-mesothelin chimeric antigen receptor according to an aspect exhibits an ability to specifically bind to mesothelin, and thus may be usefully applied to preventing or treating mesothelin-overexpressing cancers.
Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2retmlWjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom Il2rgtmlWjl/SzJ (NRG) and NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.
Type:
Grant
Filed:
May 28, 2020
Date of Patent:
October 17, 2023
Assignees:
The Jackson Laboratory, University of Massachusetts
Inventors:
Leonard D. Shultz, Mohit Kumar Verma, Dale L. Greiner, Michael A. Brehm
Abstract: Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.
Type:
Grant
Filed:
September 2, 2022
Date of Patent:
October 10, 2023
Assignee:
Akouos, Inc.
Inventors:
Emmanuel John Simons, Ellen Reisinger, Sebastian Kügler, Hanan Al-Moyed
Abstract: Compositions and methods for mitochondria genome editing are provided. Also provided are methods for treating mitochondrial disorders by the disclosed compositions.
Type:
Grant
Filed:
June 9, 2017
Date of Patent:
October 10, 2023
Assignees:
City of Hope, The Regents of the University of California
Abstract: The present invention relates to compositions and methods of generating modified hematopoietic stem or progenitor cells. One aspect of the invention includes a modified hematopoietic stem or progenitor cell comprising a nucleic acid capable of decreasing expression of an endogenous gene or a portion thereof, wherein the endogenous gene encodes a polypeptide comprising an antigen domain targeted by a chimeric antigen receptor (CAR). Another aspect of the invention includes a method for generating a modified hematopoietic stem or progenitor cell. Also included are methods and pharmaceutical compositions comprising the modified cell for adoptive therapy and treating a condition, such as an autoimmune disease or cancer.
Type:
Grant
Filed:
December 19, 2019
Date of Patent:
October 3, 2023
Assignee:
The Trustees of the University of Pennsylvania
Abstract: The presently disclosed subject matter provides compositions and methods comprising improvements of a CRISPR system (e.g. CRISPR associated (Cas) 9 (CRISPR-Cas9, non-Cas9 CRISPR systems). Such compositions may comprise modifications to the H1 promoter region, addition of 5?UTR modifications, different orthologous sequences of the H1 promoter, novel compact bidirectional promoter sequences with both pol II and pol III activity, addition of Kozak consensus sequences, termination sequences, addition of conditional pol II/pol III bidirectional promoter expression, addition of a donor template sequence for correcting mutations, or combinations thereof. Other aspects of the invention relate to modifications to Cas9 through post-transcriptional cell-cycle regulation fusions, engineered partial target sites such that the nuclease can bind without DNA cleavage, auto-regulation sites, and N-terminal modifications to modulate half-life.
Type:
Grant
Filed:
July 5, 2017
Date of Patent:
September 26, 2023
Assignee:
The Johns Hopkins University
Inventors:
Vinod Jaskula-Ranga, Donald Zack, Derek Welsbie
Abstract: Techniques regarding the transportation and/or delivery of molecular cargo by exosomes are provided. For example, one or more embodiments described herein can comprise a molecule, which can comprise a chemically modified molecular cargo bonded to a surface biomolecule of an exosome. The surface biomolecule can be located on a bilayer membrane of the exosome opposite a cytoplasm of the exosome.
Type:
Grant
Filed:
January 3, 2019
Date of Patent:
September 26, 2023
Assignee:
INTERNATIONAL BUSINESS MACHINES CORPORATION
Abstract: Provided is an adeno-associated virus (AAV) complex for expression of an RUNX3 gene including an asymmetrically modified inverted terminal repeat (ITR). The AAV complex has asymmetric ITRs in which one of the two ITRs is modified, thereby increasing self-replication efficiency in host cells and increasing expression efficiency of a delivered gene, and therefore, compared to existing AAV complexes, the AAV complex has an advantage of improved productivity and gene expression efficiency.
Type:
Grant
Filed:
March 27, 2023
Date of Patent:
September 26, 2023
Assignee:
GENECRAFT, INC.
Inventors:
Suk Chul Bae, You Soub Lee, Xinzi Chi, Ja Yeol Lee
Abstract: Provided herein are engineered cells, comprising: a chemical or biological moiety covalently bound to a cell surface glycan, wherein the chemical or biological moiety is selected from the group consisting of small molecule, polynucleotide, polypeptide, and antibody. Also provided are compositions comprising these engineered cells and methods of making and using the same.
Type:
Grant
Filed:
February 1, 2018
Date of Patent:
September 12, 2023
Assignee:
The Scripps Research Institute
Inventors:
Peng Wu, Jie Li, Yiran Zhou, Mingkuan Chen
Abstract: The present invention relates to a method for producing a liquid composition comprising a nanoparticle comprising at least one RNA and at least one cationic or polycationic compound, advantageously on a large scale suitable for pharmaceutical applications. The present invention further concerns the use of the inventive method in the manufacture of a medicament or a vaccine. Furthermore, the invention relates to compositions containing the RNA-comprising nanoparticle, and to pharmaceutical compositions comprising the same.
Type:
Grant
Filed:
April 2, 2020
Date of Patent:
September 5, 2023
Assignee:
CureVac Manufacturing GmbH
Inventors:
Thorsten Mutzke, Markus Kreuz, Stefanie Sewing, Fabian Johannes Eber, Wenke Wagner, Michael Sonntag, Michael Wiggenhorn, Katharina Kolland
Abstract: The invention pertains to a lipid-based microbubble stably binding a plurality of nucleic acids, and a method of delivering the microbubble and nucleic acids to a specific target site using ultrasound. The delivered nucleic acids create transgenic cells (i.e., for example, a transgenic tumor cell), wherein the transgenic cell expresses the proteins encoded by the delivered nucleic acids. This technology provides a significant improvement for microbubble-drug delivery platforms as known microbubble do not efficiently bind nucleic acids. The improvements described herein include but are not limited to identifying proper lipid proportionality ratios and/or cationic surfactant layers that provide an optimum mechanical index compatible with ultrasonics. Microbubble perfusion and/or nucleic acid delivery may be performed by a combination of imaging and ultrasound/microbubble targeted delivery to simultaneously perform low power two-dimensional imaging and high power microbubble destruction.
Type:
Grant
Filed:
March 4, 2020
Date of Patent:
August 29, 2023
Assignee:
University Of Pittsburgh—Of The Commonwealth System Of Higher Education
Inventors:
Flordeliza Villanueva, Andrew Carson, Charles F McTiernan, Jianjun Wang
Abstract: A system for manufacturing an artificial construct suitable for transplantation into a biological organism that includes a two or three three-dimensional preform that is based on the actual two or three-dimensional structure of a native mammalian tissue; and an electrospinning apparatus, wherein the electrospinning apparatus is operative to deposit at least one layer of polymer fibers on the preform to form a polymer scaffold, and wherein the orientation of the fibers in the scaffold relative to one another is substantially parallel.
Abstract: Described herein are guide RNAs and modified guide RNAs suitable for biallelic correction of Pompe disease. Also included are methods of modifying a target gene in a patient or in a patient-derived cell, wherein the patient has an autosomal recessive disorder with compound heterozygous mutations, the methods including delivering a first modified guide RNA, a second modified guide RNA, a Cas9 polypeptide, a biotin-binding molecule, a first biotinylated donor polynucleotide, and a second biotinylated donor polynucleotide. The first modified guide RNA and the first biotinylated donor polynucleotide correct a first diseased allele, and the second modified guide RNA and the second biotinylated donor polynucleotide correct a second diseased allele.
Type:
Grant
Filed:
November 5, 2019
Date of Patent:
August 29, 2023
Assignee:
WISCONSIN ALUMNI RESEARCH FOUNDATION
Inventors:
Krishanu Saha, Jared Matthew Carlson-Stevermer, Lucille Katherine Kohlenberg
Abstract: Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.
Type:
Grant
Filed:
December 21, 2021
Date of Patent:
August 22, 2023
Assignee:
TRANSLATE BIO, INC.
Inventors:
Braydon Charles Guild, Frank DeRosa, Michael Heartlein