公开(公告)号：US20230066806A1

公开(公告)日：2023-03-02

申请号：US17439328

申请日：2020-03-13

申请人： The Regents of the University of California

发明人： Theodore Lee Roth ,  Po-Yi Jonathan Li ,  Alexander Marson ,  Jasper Nies ,  Cody Mowery ,  Eric Shifrut ,  Franziska Blaeschke ,  Ryan Apathy

IPC分类号： C12N15/10 ,  C12N15/90 ,  A61K35/17 ,  A61P35/00 ,  A61P17/00

摘要： Provided herein are methods and compositions for identifying a targeted genomic insertion in a cell. Also provided are heterologous polypeptides that are co-expressed under the control of enodogenous loci and methods of using same.

公开(公告)号：US11331346B2

公开(公告)日：2022-05-17

申请号：US17390673

申请日：2021-07-30

申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

发明人： Theodore Lee Roth ,  Eric Shifrut ,  Alexander Marson ,  Cristina Puig Saus ,  Antoni Ribas

IPC分类号： A61K35/17 ,  C07K14/725 ,  C12N9/22 ,  C12N15/113 ,  C12N15/85 ,  C12N15/90

摘要： Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

公开(公告)号：US20220017882A1

公开(公告)日：2022-01-20

申请号：US17312191

申请日：2019-12-12

申请人： The Regents of the University of California

发明人： Alexander Marson ,  Theodore Lee Roth ,  Daniel Goodman ,  David-Huy Nhu Nguyen ,  Francis C. Szoka

IPC分类号： C12N9/22 ,  C12N15/11 ,  C12N15/90

摘要： The disclosure provides compositions and methods for modifying a target nucleic acid. In some embodiments, a composition can include a targetable nuclease, a DNA-binding protein, and a donor template comprising a homology directed repair (HDR) template and one or more DNA-binding protein target sequences. In some embodiments, a composition can include a Cas protein, one or more single guide RNAs (sgRNAs), and an anionic polymer.

公开(公告)号：US20210340496A1

公开(公告)日：2021-11-04

申请号：US17284396

申请日：2019-10-10

申请人： The Regents of the University of California

发明人： Alexander Marson ,  Jessica T. Cortez ,  Jeffrey A. Bluestone ,  Eric Shifrut ,  Frederic Van Gool

IPC分类号： C12N5/0783 ,  C12N15/90 ,  A61K35/17 ,  C12N15/11 ,  C12N9/22

摘要： Provided herein are compositions and methods for modifying regulatory T cells. The inventors have identified nuclear factors that influence expression of Foxp3, a key transcriptional regulator of Treg cells. Treg cells can be modified by inhibiting and/or overexpressing one or more of these nuclear factors to produce stabilized Treg cells or destabilized Treg cells.

公开(公告)号：US20190388469A1

公开(公告)日：2019-12-26

申请号：US15547418

申请日：2016-01-29

申请人： The Regents of the University of California

发明人： Alexander Marson ,  Jennifer Doudna ,  Jeffrey Bluestone ,  Kathrin Schumann ,  Steven Lin

IPC分类号： A61K35/17 ,  C12N15/10 ,  C12N5/0789 ,  C12N15/113 ,  C12N15/90 ,  C12N9/22

摘要： Methods and compositions are provided for highly efficient delivery of Cas9 and Cas9 ribonucleoproteins to cells, including primary hematopoietic cells and primary hematopoietic stem cells.

公开(公告)号：US11590171B2

公开(公告)日：2023-02-28

申请号：US17725478

申请日：2022-04-20

申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

发明人： Theodore Lee Roth ,  Eric Shifrut ,  Alexander Marson ,  Cristina Puig Saus ,  Antoni Ribas

IPC分类号： A61K35/17 ,  C07K14/725 ,  C12N9/22 ,  C12N15/113 ,  C12N15/85 ,  C12N15/90

摘要： Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

公开(公告)号：US20210388362A1

公开(公告)日：2021-12-16

申请号：US17326252

申请日：2021-05-20

申请人： The Regents of the University of California

发明人： Theodore Lee Roth ,  Alexander Marson

IPC分类号： C12N15/113 ,  C12N9/22 ,  C12N15/10 ,  C12N15/90

摘要： Provided herein are methods and compositions for editing the genome of a cell. In some embodiments, a nucleotide sequence of at least 200 nucleotides in length is inserted into a target region in the genome of a cell.

公开(公告)号：US11033584B2

公开(公告)日：2021-06-15

申请号：US16568116

申请日：2019-09-11

申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

发明人： Theodore Lee Roth ,  Eric Shifrut ,  Alexander Marson ,  Cristina Puig Saus ,  Antoni Ribas

IPC分类号： A61K35/17 ,  C07K14/725 ,  C12N9/22 ,  C12N15/113 ,  C12N15/85 ,  C12N15/90

摘要： Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

公开(公告)号：US20210147841A1

公开(公告)日：2021-05-20

申请号：US17089284

申请日：2020-11-04

申请人： The Regents of the University of California

发明人： Alexander Marson ,  Jeffrey A. Bluestone ,  Kathrin Schumann

IPC分类号： C12N15/113 ,  C12N9/22 ,  C12N5/0783

摘要： The disclosure features methods directed to modifying regulatory T (Treg) cell stability by inhibiting the expression of one or more transcription factors and/or inhibiting one or more genes or gene products regulated by the transcription factors. The disclosure also features compositions comprising the Treg cells having modified stability.

公开(公告)号：US11639495B2

公开(公告)日：2023-05-02

申请号：US16455118

申请日：2019-06-27

申请人： The Regents of the University of California ,  Berkeley Lights, Inc.

发明人： Alexander Marson ,  Gregory G. Lavieu ,  Annamaria Mocciaro ,  Theodore L. Roth ,  Magali Soumillon ,  Hayley M. Bennett

IPC分类号： C12N5/0783 ,  B01L3/00 ,  C12N15/10

摘要： Methods are described herein for isolating clonal populations of T cells having a defined genetic modification. The methods are performed, at least in part, in a microfluidic device comprising one or more sequestration pens. The methods include the steps of: maintaining individual T cells (or precursors thereof) that have undergone a genomic editing process in corresponding sequestration pens of a microfluidic device; expanding the T cells into respective clonal populations of T cells; detecting, in one or more T cells of each clonal population, the absence of a cell surface marker that was present in the individual T cells (or precursors thereof); and detecting, in one or more T cells of each clonal population, the presence of a first nucleic acid sequence that is indicative of the presence of an on-target genome edit in the clonal population of T cells. Also described are compositions comprising one or more clonal populations of T cells isolated according to the methods disclosed herein.