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1
US20190029237A1
Publication/Patent Number: US20190029237A1
Publication date: 2019-01-31
Application number: 16/024,204
Filing date: 2018-06-29
Abstract: A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses human immunoglobulin light chain variable domains derived from a limited repertoire of human immunoglobulin light chain variable gene segments that comprise histidine modifications in their germline sequence. Methods of making non-human animals that express antibodies comprising histidine residues encoded by histidine codons introduced into immunoglobulin light chain nucleotide sequences are provided. A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses human immunoglobulin light chain ...more ...less
2
US20190029238A1
Publication/Patent Number: US20190029238A1
Publication date: 2019-01-31
Application number: 15/552,698
Filing date: 2016-02-23
Abstract: The present invention provides a transgenic mouse and an animal model that is used to assay for the inhibition or activation of the Cnr2 gene and methods for screening drugs to treat or prevent psychosis, anxiety, depression, autism disorders, drug addiction, Parkinson's disease and/or Alzheimer's disease, multiple sclerosis, inflammation, stroke, osteoporosis, scleroderma or cancer. The present invention provides a transgenic mouse and an animal model that is used to assay for the inhibition or activation of the Cnr2 gene and methods for screening drugs to treat or prevent psychosis, anxiety, depression, autism disorders, drug addiction, Parkinson's disease ...more ...less
3
US20190032156A1
Publication/Patent Number: US20190032156A1
Publication date: 2019-01-31
Application number: 16/050,822
Filing date: 2018-07-31
Abstract: Methods and compositions are provided for assessing CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo or ex vivo. The methods and compositions employ non-human animals comprising a CRISPR reporter such as a genomically integrated CRISPR reporter for detecting and measuring CRISPR/Cas-induced repair of a coding sequence for a catalytically inactive reporter protein through recombination with an exogenous donor nucleic acid. Methods and compositions are also provided for making and using these non-human animals. Methods and compositions are provided for assessing CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo or ex vivo. The methods and compositions employ non-human animals comprising a CRISPR reporter such as a genomically ...more ...less
4
US20190062696A1
Publication/Patent Number: US20190062696A1
Publication date: 2019-02-28
Application number: 16/109,218
Filing date: 2018-08-22
Abstract: The present invention provides NRP1 as a cell surface marker for isolating human cardiomyogenic ventricular progenitor cells (HVPs), in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Additional HVP cell surface markers identified by single cell sequencing are also provided. The invention provides in vitro methods of the separation of NRP1+ ventricular progenitor cells, and the large scale expansion and propagation thereof. Large clonal populations of isolated NRP1+ ventricular progenitor cells are also provided. Methods of in vivo use of NRP1+ ventricular progenitor cells for cardiac repair or to improve cardiac function are also provided. Methods of using the NRP1+ ventricular progenitor cells for cardiac toxicity screening of test compounds are also provided. The present invention provides NRP1 as a cell surface marker for isolating human cardiomyogenic ventricular progenitor cells (HVPs), in particular progenitor cells that preferentially differentiate into cardiac ventricular muscle cells. Additional HVP cell surface markers ...more ...less
5
US20190062790A1
Publication/Patent Number: US20190062790A1
Publication date: 2019-02-28
Application number: 15/915,020
Filing date: 2018-03-07
Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms. The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further ...more ...less