公开(公告)号：US20220169988A1

公开(公告)日：2022-06-02

申请号：US17538699

申请日：2021-11-30

申请人： CRISPR THERAPEUTICS AG

发明人： Viktoriia KYRYCHENKO ,  Wai Lun LEUNG ,  Alireza REZANIA ,  Valentin SLUCH ,  Danielle SWAIN ,  Patrick Claudio OVANDO ROCHE

IPC分类号： C12N5/0783 ,  C12N5/074 ,  C12N5/0735 ,  C12N5/10 ,  C12N15/66

摘要： The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

公开(公告)号：US20220169700A1

公开(公告)日：2022-06-02

申请号：US17538566

申请日：2021-11-30

申请人： CRISPR THERAPEUTICS AG

发明人： Viktoriia KYRYCHENKO ,  Wai Lun LEUNG ,  Alireza REZANIA ,  Valentin SLUCH ,  Danielle SWAIN ,  Patrick Claudio OVANDO ROCHE

IPC分类号： C07K14/74 ,  C07K14/54 ,  C07K14/715 ,  C07K14/81 ,  A61K35/17 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  C12N15/90

摘要： The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

公开(公告)号：US20230016422A1

公开(公告)日：2023-01-19

申请号：US17830273

申请日：2022-06-01

申请人： CRISPR THERAPEUTICS AG

发明人： Valentin SLUCH ,  Danielle SWAIN ,  Alireza REZANIA

IPC分类号： C12N15/90 ,  C12N9/22 ,  C12N5/074

摘要： Provided herein are cells engineered to have improved protection against natural killer cell killing. The cells are engineered to comprise an insertion of a polynucleotide encoding SERPINB9. Also provided herein are methods of making the engineered cells and therapeutic uses of the engineered cells. The engineered cells can also comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor. The engineered cells can be stem cells and the engineered stem cells can be differentiated into various lineages having protection against NK cell killing.

公开(公告)号：US20230227532A1

公开(公告)日：2023-07-20

申请号：US18068056

申请日：2022-12-19

申请人： CRISPR Therapeutics AG

发明人： Valentin SLUCH ,  Alireza REZANIA ,  Jason SAGERT ,  Danielle SWAIN

IPC分类号： C07K14/74 ,  C07K14/54 ,  C12N5/0735 ,  C12N5/0783 ,  C12N5/10 ,  C07K14/81 ,  C07K14/715 ,  C07K16/28 ,  C12N15/66 ,  C07K14/725 ,  A61K35/17 ,  C12N5/074 ,  C12N15/90

CPC分类号： C07K14/70539 ,  C07K14/5443 ,  C12N5/0606 ,  C12N5/0646 ,  C12N5/10 ,  C07K14/8121 ,  C07K14/7155 ,  C07K16/2878 ,  C12N15/66 ,  C07K14/7051 ,  A61K35/17 ,  C12N5/0696 ,  C12N15/907 ,  C12N2510/00 ,  C12N2310/20 ,  C12N2506/11 ,  C07K2319/00

摘要： The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

公开(公告)号：US20230014010A1

公开(公告)日：2023-01-19

申请号：US17830278

申请日：2022-06-01

申请人： CRISPR THERAPEUTICS AG

发明人： Valentin SLUCH ,  Danielle SWAIN ,  Alireza REZANIA

IPC分类号： C12N15/90 ,  C12N5/074 ,  C12N15/85 ,  C12N15/62 ,  C07K14/81 ,  C07K14/74 ,  C07K14/54 ,  C07K14/715 ,  C12N5/0783 ,  C12N5/071

摘要： Provided herein are cells engineered to have improved protection against natural killer cell killing. The cells are engineered to comprise an insertion of a polynucleotide encoding SERPINB9. Also provided herein are methods of making the engineered cells and therapeutic uses of the engineered cells. The engineered cells can also comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor. The engineered cells can be stem cells and the engineered stem cells can be differentiated into various lineages having protection against NK cell killing.