Patents by Inventor Ling-Jie Kong
Ling-Jie Kong has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 11959093Abstract: The present disclosure provides compositions and methods for enhanced expression of exogenous genes in eukaryotic cells. The method involves introducing into a mammalian cell an exogenous nucleic acid. wherein the exogenous nucleic acid intearates into a locus of the genome that comprises an extended methylation-free CpG island. Also provided are chromosomal loci, sequences for enhanced and stable expression of exogenous genes.Type: GrantFiled: March 14, 2018Date of Patent: April 16, 2024Assignee: APPLIED STEMCELL, INC.Inventors: Ling-Jie Kong, Ruby Yanru Tsai, Xiuling Chi
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Patent number: 11647737Abstract: Provided is a genetically modified non-human mammal that comprises an anchor DNA sequence inserted at an endogenous locus of a secretory milk protein gene, wherein the anchor DNA sequence comprises a site-specific recombinase recognition site. Also provided is a genetically modified non-human mammal that comprises a transgene inserted at an endogenous locus of a secretory milk protein gene, wherein the transgene encodes a secretory protein and is operably linked to the endogenous promoter of said secretory milk protein gene, and wherein the transgene is flanked by a pair of site-specific recombinase resulting sites. The genetically modified non-human mammals provided can be used for producing the secreted recombinant protein encoded by the transgene from the milk produced by the genetically modified non-human mammals.Type: GrantFiled: December 29, 2017Date of Patent: May 16, 2023Assignees: ASC THERAPEUTICS INC., THE REGENTS OF THE UNIVERSITY OF MICHIGANInventors: Ruby Yanru Tsai, Jie Xu, Yuqing Chen, Jifeng Zhang, Ling-Jie Kong
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Patent number: 11597947Abstract: Provided is a method of inserting a polynucleotide sequence into a genome of a cell. The method comprises: generating a double-strand break at a target site of the genome; and introducing into the cell a virus. The virus comprises a nucleic acid comprising the polynucleotide sequence to be inserted or the complementary sequence thereof. The nucleic acid does not comprise a homologous arm or comprises very short (5˜25 bp) homologous arms corresponding to the target site. Also provided herein is a composition for inserting a polynucleotide sequence into a genome of a cell. The composition comprises a site-specific nuclease capable of generating a DNA double-strand break at a target site of the genome and a virus comprising a nucleic acid comprising the polynucleotide sequence or the complementary sequence thereof.Type: GrantFiled: December 29, 2017Date of Patent: March 7, 2023Assignee: ASC THERAPEUTICS INC.Inventors: Ling-Jie Kong, Mi Shi, Hainan Chen, Ruby Yanru Tsai
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Publication number: 20220380756Abstract: Provided herein are methods and compositions for treating genetic blood cell diseases, e.g. sickle cell disease and thalassemia, by correcting genetic mutation or inserting exogenous globin gene using CRISPR/Cas system.Type: ApplicationFiled: June 29, 2020Publication date: December 1, 2022Inventors: Xuefeng WANG, Ling-jie KONG, H. Steve ZHANG, Ruby Yanru TSAI
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Patent number: 11505792Abstract: Provided is a method for knocking in a gene of interest to a cell. The genome of the cell contains a negative selectable marker, e.g., a thymidine kinase gene flanked by a pair of recombinase recognition sites (RRS), e.g., attP. The method involves introducing into the cell a targeting construct that contains a gene of interest flanked by a second pair of RRS, e.g., attB. The targeting construct also contains in the vector backbone a negative selectable marker, e.g., thymidine kinase gene. When a recombinase recognizing the RRS is expressed, the recombination events between the two pairs of RRS result in the site-specific integration of the gene of interest in the genome of the cell. Upon selection based on the negative selectable marker, the parental cells, cells with undesired integration, e.g., random integration, or the integration of the vector backbone are removed.Type: GrantFiled: April 11, 2017Date of Patent: November 22, 2022Assignee: APPLIED STEMCELL, INC.Inventors: Ling-jie Kong, Ruby Yanru Tsai
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Publication number: 20220340935Abstract: Provided herein are methods for producing a cell having chromosome translocation, deletion or reversion. In one embodiment, the method for producing a cell having chromosome translocation comprises introducing site-specific nucleases to the cell to create double strand breaks in a first and a second chromosome; generating an intermediate fusion chromosome comprising a first segment of the first chromosome, a selection region and the second segment of a second chromosome; and creating double strand breaks at sites that flank the selection region, thereby generating a fusion chromosome comprising at least part of the first segment of the first chromosome linked to at least part of the second segment of the second chromosome.Type: ApplicationFiled: June 19, 2020Publication date: October 27, 2022Inventors: Qi ZHENG, Ling-jie KONG, Ruby Yanru TSAI
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Patent number: 11339408Abstract: The present disclosure provides a composition comprising a site-specific nuclease domain capable of cleaving a target DNA sequence; and a sequence-specific DNA binding domain capable of specifically binding to a recognition DNA sequence, wherein the site-specific nuclease domain operably links to the sequence-specific DNA binding domain.Type: GrantFiled: August 22, 2016Date of Patent: May 24, 2022Assignee: APPLIED STEMCELL, INC.Inventors: Ruby Yanru Tsai, Ling-jie Kong, Jingyuan Cao
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Publication number: 20220127642Abstract: Provided herein are compositions and methods for genome editing and modification. In one embodiment, the composition comprises a regulatory gene expression construct that comprises a nucleic acid encoding an RNA comprising a sequence encoding a genome editing enzyme and a regulatory cassette operably linked to the sequence. In one embodiment, the regulatory cassette comprises a conditional exon and an aptamer domain which is capable of binding to an effector molecule to trigger a structural change of the RNA, thereby regulating splicing of the conditional exon and expression of the genome editing enzyme.Type: ApplicationFiled: January 30, 2020Publication date: April 28, 2022Inventors: Ruby Yanru TSAI, Alfonso Pedro FARRUGGIO, Armon KHOSRAVIANI, Naisargi Shaileshkumar PATEL, Ling-Jie KONG
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Publication number: 20210284715Abstract: The present disclosure provides a coagulation factor VIII(FVII) mimetic protein. The FVIII mimetic protein comprises (1) a coagulating factor IX (FIX/FIXa) binding domain comprising a first heavy chain variable region (VHI) and a first light chain variable region (VL1), wherein the VH1 and the VL1 are derived from an antibody specifically binding to FIX/FIXa; (2) a coagulation factor X (FX) binding domain comprising a second heavy chain variable region (VH2) and a second light chain variable region (VL2), wherein the VH2 and the VL2 are derived from an antibody specifically binding to FX; and (3) a membrane binding domain.Type: ApplicationFiled: February 6, 2018Publication date: September 16, 2021Inventors: Ling-jie KONG, Ruby Yanru TSAI, Xiuling CHI
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Publication number: 20210198696Abstract: Provided is a method of inserting a polynucleotide sequence into a genome of a cell. The method comprises: generating a double-strand break at a target site of the genome; and introducing into the cell a virus. The virus comprises a nucleic acid comprising the polynucleotide sequence to be inserted or the complementary sequence thereof. The nucleic acid does not comprise a homologous arm or comprises very short (5˜25 bp) homologous arms corresponding to the target site. Also provided herein is a composition for inserting a polynucleotide sequence into a genome of a cell. The composition comprises a site-specific nuclease capable of generating a DNA double-strand break at a target site of the genome and a virus comprising a nucleic acid comprising the polynucleotide sequence or the complementary sequence thereof.Type: ApplicationFiled: December 29, 2017Publication date: July 1, 2021Inventors: Ling-jie KONG, Mi SHI, Hainan CHEN, Ruby Yanru TSAI
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Publication number: 20210030851Abstract: Provided herein are compositions and methods for enhancing expression of SMN protein in a cell. In one embodiment, the composition comprises a site-specific nuclease targeting the ISS-N1 region of human SMN2 gene. Also provided are compositions and methods for treating or ameliorating spinal muscular atrophy.Type: ApplicationFiled: October 16, 2020Publication date: February 4, 2021Inventors: Ling-jie KONG, Ruby Yanru TSAI, Zoya GLUZMAN-POLTORAK, Ivka AFRIKANOVA
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Publication number: 20200017884Abstract: The present disclosure provides compositions and methods for enhanced expression of exogenous genes in eukaryotic cells. Also provided are chromosomal loci, sequences for enhanced and stable expression of exogenous genes.Type: ApplicationFiled: March 14, 2018Publication date: January 16, 2020Inventors: Ling-jie KONG, Ruby Yanru TSAI, Xiuling CHI
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Publication number: 20190335729Abstract: Provided is a genetically modified non-human mammal that comprises an anchor DNA sequence inserted at an endogenous locus of a secretory milk protein gene, wherein the anchor DNA sequence comprises a site-specific recombinase recognition site. Also provided is a genetically modified non-human mammal that comprises a transgene inserted at an endogenous locus of a secretory milk protein gene, wherein the transgene encodes a secretory protein and is operably linked to the endogenous promoter of said secretory milk protein gene, and wherein the transgene is flanked by a pair of site-specific recombinase resulting sites. The genetically modified non-human mammals provided can be used for producing the secreted recombinant protein encoded by the transgene from the milk produced by the genetically modified non-human mammals.Type: ApplicationFiled: December 29, 2017Publication date: November 7, 2019Inventors: Ruby Yanru TSAI, Jie XU, Yuqing CHEN, Jifeng ZHANG, Ling-jie KONG
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Publication number: 20190078076Abstract: Provided is a method for knocking in a gene of interest to a cell. The genome of the cell contains a negative selectable marker, e.g., a thymidine kinase gene flanked by a pair of recombinase recognition sites (RRS), e.g., attP. The method involves introducing into the cell a targeting construct that contains a gene of interest flanked by a second pair of RRS, e.g., attB. The targeting construct also contains in the vector backbone a negative selectable marker, e.g., thymidine kinase gene. When a recombinase recognizing the RRS is expressed, the recombination events between the two pairs of RRS result in the site-specific integration of the gene of interest in the genome of the cell. Upon selection based on the negative selectable marker, the parental cells, cells with undesired integration, e.g., random integration, or the integration of the vector backbone are removed.Type: ApplicationFiled: April 11, 2017Publication date: March 14, 2019Inventors: Ling-jie KONG, Ruby Yanru TSAI
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Publication number: 20180216135Abstract: The present disclosure provides a composition comprising a site-specific nuclease domain capable of cleaving a target DNA sequence; and a sequence-specific DNA binding domain capable of specifically binding to a recognition DNA sequence, wherein the site-specific nuclease domain operably links to the sequence-specific DNA binding domain.Type: ApplicationFiled: August 22, 2016Publication date: August 2, 2018Inventors: Ruby Yanru TSAI, Ling-jie KONG, Jingyuan CAO
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Patent number: 6800793Abstract: Transgenic plants with increased resistance to geminivirus infection, and nucleic acid constructs useful in producing such plants, are described. The transgenic plants express a mutant AL1/C1 geminivirus protein, which increases resistance to infection by at least one geminivirus, compared to a non-transformed control plant.Type: GrantFiled: April 9, 1999Date of Patent: October 5, 2004Assignees: North Carolina State University, Regents of the University of CaliforniaInventors: Linda Hanley-Bowdoin, Beverly M. Orozco, Ling-Jie Kong, Wilhelm Gruissem
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Publication number: 20020138867Abstract: Transgenic plants with increased resistance to geminivirus infection, and nucleic acid constructs useful in producing such plants, are described. The transgenic plants express a mutant AL1/C1 geminivirus protein, which increases resistance to infection by at least one geminivirus, compared to a non-transformed control plant.Type: ApplicationFiled: April 9, 1999Publication date: September 26, 2002Inventors: LINDA HANLEY-BOWDOIN, BEVERLY M. OROZCO, LING-JIE KONG, WILHELM GRUISSEM