Abstract: A genetically modified rodent is provided that comprises a modified Acvr1 gene that comprises a conditional altered exon 7 encoding R258G in anti sense orientation, flanked by site-specific recombinase recognition sites, wherein the altered exon is inverted to sense orientation upon action of a recombinase, resulting in ectopic bone formation.
Type:
Grant
Filed:
June 12, 2019
Date of Patent:
August 23, 2022
Assignee:
Regeneran Pharmaceuticals, Inc.
Inventors:
Sarah J. Hatsell, Aris N. Economides, Christopher Schoenherr, Vincent J. Idone
Abstract: A stem cell removing method that certainly-removes an undifferentiated stem cell is provided. For this object, a cell group including a stem cell and a somatic cell performed differentiation induction is cultivated in culture medium composition including photosensitizer. Light of a specific wavelength is irradiated with the cell group, and the stem cell is removed, selectively. The stem cell is a pluripotent stem cell or a somatic stem cell. The pluripotent stem cell includes either an ES cell (Embryonic Stem Cell) or an iPS cell (induced Pluripotent Stem Cell). Also, somatic stem cell includes any one of a germ stem cell, a productive cell, a pluripotent stem cell and a stem cell having unipotency.
Abstract: A cell product for prevention and/or treatment of vascular disorders such as aortic aneurysm, comprising a SSEA-3-positive pluripotent stem cell derived from a mesenchymal tissue in a living body or a cultured mesenchymal cell (Muse cell).
Type:
Grant
Filed:
July 28, 2017
Date of Patent:
August 23, 2022
Assignees:
TOHOKU UNIVERSITY, LIFE SCIENCE INSTITUTE INC.
Inventors:
Yoshikatsu Saiki, Mari Dezawa, Katsuhiro Hosoyama
Abstract: The present disclosure provides methods of generating multiplexed genetically modified animals, for example, porcine endogenous retrovirus (PERV)-inactivated pigs. The disclosure also provides methods of improving the birth rate of multiplexed genetically modified animals. In some embodiments, the present closure is concerned with the generation and utilization of porcine cells in which porcine endogenous retroviral (PERV) elements have been inactivated. In sonic embodiments, the PERV-free or PERV-reduced porcine cells are cloned to produce porcine embryos. In some embodiments, the PERV-free or PERV-reduced embryos may be grown into adult swine from which organs and/or tissues may be extracted and used for such purposes as xenotransplantation into non-porcine animals such as humans.
Type:
Grant
Filed:
September 30, 2019
Date of Patent:
August 9, 2022
Assignees:
BIOMARIN PHARMACEUTICAL INC., UCL BUSINESS LTD, ST. JUDE CHILDREN'S RESEARCH HOSPITAL
Inventors:
Peter Cameron Colosi, Amit Nathwani, Jenny McIntosh, Edward Tuddenham, Andrew Davidoff
Abstract: Provided herein non-human transgenic animals comprising a genome that: i) under-expresses, or is inducible to under-express, Hu Antigen R (HuR) in at least some neurons of said transgenic animal; ii) does not express HuR, or is inducible to not express HuR, in at least some neurons of said transgenic animal; or iii) does not express functional HuR, or is inducible to not express functional HuR in at least some neurons of said transgenic animal, as well as methods of screening drugs and therapies (e.g., useful in treating ALS) using such animals.
Type:
Grant
Filed:
June 19, 2019
Date of Patent:
July 12, 2022
Assignee:
The Cleveland Clinic Foundation
Inventors:
Xiaoxia Li, Tomasz Herjan, Kevin Sun, Xing Chen
Abstract: The present invention relates to processes for transfecting cells. In particular, the present invention relates to processes for using CRISPR to incorporate a polynucleotide into the genome of an avian primordial germ cell (PGC).
Type:
Grant
Filed:
April 15, 2019
Date of Patent:
June 28, 2022
Assignees:
COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH ORGANISATION, AVIAGEN
Abstract: An improvement to the GiWi protocol for differentiating human pluripotent cells to developmentally mature cardiomyocytes includes a step of activating innate immunity in mesoderm stage cells in the in vitro differentiation culture. When the mesoderm cells, which are precursors to cardiac progenitor cells, are primed by exposure to an activator of innate immunity, a population of cardiomyocytes is generated that is more developmentally mature than is generated in the GiWi protocol without the primed step. Also provided herein are in vitro ventricular conductive microtissues and isolated, in vitro populations of ventricular conduction system-like cells and methods for making the same.
Type:
Grant
Filed:
September 29, 2017
Date of Patent:
June 7, 2022
Assignee:
Wisconsin Alumni Research Foundation
Inventors:
Mitch James Biermann, Timothy Joseph Kamp
Abstract: A method of producing a non-erythroid protein in erythrocytes of a transgenic animal using an erythroid-specific promoter includes synthesizing an erythroid-specific globin gene promoter and globin gene locus control region and cloning the promoter and the globin gene locus control region and a gene encoding a non-erythroid protein into a vector to obtain a transgene; introducing the transgene in pronuclear embryos collected from a mammalian animal in vitro; transplanting the pronuclear embryos containing the transgene into oviduct of a female recipient of the mammalian animal to obtain a transgenic animal which then expresses the non-erythroid protein in progenitor cells of erythrocytes; and collecting blood from the transgenic animal and isolating the non-erythroid protein from the erythrocytes.
Type:
Grant
Filed:
March 7, 2019
Date of Patent:
May 31, 2022
Inventors:
Hai Xing Chen, Hong Yang Wang, Zhongtian Qi
Abstract: The present invention relates to the production of avian induced pluripotent stem cells from non-pluripotent somatic cells, including embryonic fibroblasts and adult somatic cells. In this method, avian (including quail or chicken) somatic cells are reprogrammed into a state closely resembling embryonic stem cells including the expression of key stem cell markers alkaline phosphatase, etc. by transfecting/transducing the non-stem cells with genes (preferably using a non-integrating vector as otherwise described herein or alternatively an integrating vector, such a lentiviral vector, retroviral vector or inducible lentiviral vector, among others) which express at least nanog, Lin28 and cMyc. In preferred aspects of the invention, the transfected/transduced vectors express nanog, Lig28, cMyc, Oct 4 (POU5F1 or PouV), SOX2 and KLF4. The induced stem cells which are produced contribute to all 3 germ layers, the trophectoderm and in certain aspects, the gonad in chimeric offspring.
Type:
Grant
Filed:
November 4, 2019
Date of Patent:
May 17, 2022
Assignee:
UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.
Inventors:
Steven L Stice, Franklin West, Yangqing Lu
Abstract: A method of constructing a zebrafish notch1a mutant using CRISPR/Cas9 technique. The method includes: determining a target for knocking out notch1a; using primers T7-notch1a-sfd and tracr rev for PCR amplification with a pUC19-gRNA scaffold plasmid as a template; transcribing PCR product in vitro followed by purification to obtain gRNA; and microinjecting the gRNA and a Cas9 mRNA into a zebrafish embryo followed by culture to obtain an notch1a mutant of stable inheritance. The invention selects a specific target and utilizes CRISPR/Cas9 technique to knock out the notch1a in the zebrafish without destroying other genes, generating the zebrafish notch1a mutant. Moreover, the invention also discloses the phenotype of the zebrafish notch1a mutant, which plays a significant role in studying the effect of the Notch1a receptor in the Notch signaling pathway.
Abstract: Provided herein is a cell line with improved odorant receptor function comprising an activated endogenous RTP1 gene, which further expresses an RTP1 protein. Further provided herein is a method for specifically activating an endogenous RTP1 gene in a eukaryotic cell using a CRISPR/Cas9 derived technique. Also provided herein is a method for identifying compounds with desired effects such as perfume or aroma modulators in said cell line.
Type:
Grant
Filed:
June 9, 2016
Date of Patent:
March 8, 2022
Assignee:
FIRMENICH SA
Inventors:
Hyo-Young Jeong, Patrick Pfister, Matthew Rogers
Abstract: Provided is a double-gene knockout vector system, a method for preparing porcine fibroblasts with both CD163 gene and CD13 gene being knocked-out, prepared porcine fibroblasts, and a method for preparing a gene-edited pig with both CD163 gene and CD13 gene being knocked-out. The vector system of the present disclosure comprises a CD163 gene knockout vector and a CD13 gene knockout vector. The CD163 gene knockout vector comprises a gene editing vector backbone and a DNA fragment ligated to the gene editing vector backbone, with a nucleotide sequence of the DNA fragment being shown in any one of SEQ ID NOs: 1-3. The CD13 gene knockout vector comprises a gene editing vector backbone and a DNA fragment ligated to the gene editing vector backbone, a nucleotide sequence of the DNA fragment being shown in any one of SEQ ID NOs: 4-6.
Type:
Grant
Filed:
April 9, 2019
Date of Patent:
February 8, 2022
Assignee:
Shandong Landsee Genetics Co., Ltd.
Inventors:
Kui Li, Yulian Mu, Zhiguo Liu, Julang Li, Kui Xu, Yinghui Wei, Changli Ge, Xuehui Cai, Long Wang, Qimei Chen, Yang Qiu
Abstract: Mice comprising a transgene encoding a peptide (iBox) inhibitor of Group B p21-activated kinase are provided. Also provided are cells, tissue, and organs obtained from such transgenic mice. Also provided are methods for producing mice comprising an iBox-encoding transgene.
Abstract: Methods of producing stem cell conditioned media to treat mammalian injuries or insults. In at least one embodiment of a method for isolating non-endothelial adipocyte-depleted stromal cells of the present disclosure, the method comprises, comprising dissociating subcutaneous adipose tissue isolated from a mammal into a cell suspension, removing adipocytes from said cell suspension, resulting in a non-endothelial adipocyte-depleted cell suspension, and culturing the non-endothelial adipocyte-depleted cell suspension in a media containing growth factors VEGF, bFGF, EGF, and IGF, such that a mixed population of cells comprising a first population of further differentiated non-endothelial adipocyte-depleted CD34+/VE-cadherin? cells and a second population of further differentiated non-endothelial adipocyte-depleted CD34+/VE-cadherin+ cells are obtained and expanded.
Abstract: Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.
Abstract: Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.
Abstract: The present invention relates to chemically defined and xenogeneic material-free methods for deriving endothelial cells from human pluripotent stem cells. In particular, the present invention provides highly efficient and reproducible methods of obtaining human endothelial cells from human pluripotent stem cells, where endothelial cells derived from the methods provided herein are suitable for clinically relevant therapeutic applications.
Abstract: The present disclosure relates methods and compositions useful for prevention of porcine reproductive and respiratory syndrome virus (PRRSv) in animals, including animals of the species Sus scrofa. The present teachings relate to swine wherein at least one allele of a CD163 gene has been inactivated, and to specific methods and nucleic acid sequences used in gene editing to inactivate the CD163 gene. Swine wherein both alleles of the CD163 gene are inactivated are resistant to porcine reproductive and respiratory syndrome virus (PRRSv). Elite lines comprising homozygous CD163 edited genes retain their superior properties.
Type:
Grant
Filed:
May 4, 2021
Date of Patent:
December 28, 2021
Assignee:
Genus PLC
Inventors:
Andrew Mark Cigan, Jonathan Edward Lightner, Matthew Scott Culbertson, William Thomas Christianson, Benjamin Beaton, Brian Burger, Dylan Barnes, Matthew Campbell
Abstract: Cells derived from postpartum tissue and methods for their isolation and induction to differentiate to cells of a chondrogenic or osteogenic phenotype are provided by the invention. The invention further provides cultures and compositions of the postpartum-derived cells and products related thereto. The postpartum-derived cells of the invention and products related thereto have a plethora of uses, including but not limited to research, diagnostic, and therapeutic applications, for example, in the treatment of bone and cartilage conditions.
Type:
Grant
Filed:
June 25, 2004
Date of Patent:
December 7, 2021
Assignee:
Depuy Synthes Products, Inc.
Inventors:
Anthony J. Kihm, Agnieszka Seyda, Sridevi Dhanaraj, Ziwei Wang, Alexander M. Harmon, Ian Ross Harris, Darin J. Messina, Sanjay Mistry, Anna Gosiewska, Chin-Feng Yi
Abstract: The present disclosure relates to a medium composition for r25/eprogramming induced pluripotent stem cells, containing an Ecklonia cava extract. Also, the present disclosure relates to a method for manufacturing induced pluripotent stem cells by using the medium composition. When the medium composition according to the present disclosure is used, induced pluripotent stem cells can be efficiently produced using adipose-derived mesenchymal stem cells safely and easily. The manufactured pluripotent stem cells are differentiable into various cells, and thus can be favorably used as a cell therapeutic agent.
Type:
Grant
Filed:
June 25, 2014
Date of Patent:
November 30, 2021
Assignee:
BBHC CO., LTD.
Inventors:
Sang Yeon Lee, Won Ju Jung, Ho Bin Kim, Min Sun Oh, Kye Ho Lee