公开(公告)号：WO2022226303A1

公开(公告)日：2022-10-27

申请号：PCT/US2022/025945

申请日：2022-04-22

Applicant: PRECISION BIOSCIENCES, INC. ,  UNIVERSITY OF MIAMI

Inventor： MORAES, Carlos T. ,  SMITH, James Jefferson ,  JANTZ, Derek ,  TOMBERLIN, Ginger H. ,  MORRIS, John ,  SHOOP, Wendy

IPC: C12N9/22 ,  A61K38/43

Abstract: Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in combination with mitochondrial transit peptides in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been modified or edited.

公开(公告)号：WO2019089913A1

公开(公告)日：2019-05-09

申请号：PCT/US2018/058692

申请日：2018-11-01

Applicant: PRECISION BIOSCIENCES, INC.

Inventor： HEKELE, Armin ,  BEARD, Clayton ,  JANTZ, Derek ,  SMITH, James, Jefferson ,  BARTSEVICH, Victor

IPC: C12N9/22 ,  C12N15/861 ,  C07K14/755 ,  A61K48/00 ,  C12N15/90

CPC classification number: C12N9/22 ,  A01K2267/0381 ,  A61K48/005 ,  C07K14/755 ,  C07K2319/81

Abstract: The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within the int22h-1 sequence of a Factor VIII gene. The present invention also encompasses methods of using such engineered nucleases to make genetically- modified cells, and the use of such cells in a pharmaceutical composition and in methods for treating hemophilia A. Further, the invention encompasses pharmaceutical compositions comprising engineered nuclease proteins, nucleic acids encoding engineered nucleases, or genetically-modified cells of the invention, and the use of such compositions for treating of hemophilia A.

公开(公告)号：WO2018071849A3

公开(公告)日：2018-04-19

申请号：PCT/US2017/056638

申请日：2017-10-13

Applicant: PRECISION BIOSCIENCES, INC.

Inventor： JANTZ, Derek ,  SMITH, James, Jefferson

IPC: C12N9/22 ,  A61K38/00

Abstract: The present invention encompasses engineered meganucleases which recognize and cleave a recognition sequence within an open reading frame (ORF) of the genome of at least two genotypes of the Hepatitis B virus (HBV). The present invention also encompasses methods of using such engineered meganucleases in a pharmaceutical composition and in methods for treating or reducing the symptoms of a HBV infection, or treating hepatocellular carcinoma (HCC). Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or HCC.

公开(公告)号：WO2009134714A2

公开(公告)日：2009-11-05

申请号：PCT/US2009/041796

申请日：2009-04-27

Applicant: PRECISION BIOSCIENCES, INC. ,  NICHOLSON, Michael, G. ,  JANTZ, Derek ,  SMITH, James, Jefferson

Inventor： NICHOLSON, Michael, G. ,  JANTZ, Derek ,  SMITH, James, Jefferson

IPC: A61K48/00

CPC classification number: C12N9/22 ,  A61K48/00

Abstract: Targeted transcriptional effectors (transcription activators and transcription repressors) derived from meganucleases are described. Also described are nucleic acids encoding same, and methods of using same to regulate gene expression. The targeted transcriptional effectors can comprise (i) a meganuclease DNA-binding domain lacking endonuclease cleavage activity that binds to a target recognition site; and (ii) a transcription effector domain.

Abstract translation: 描述了衍生自大范围核酸酶的靶向转录效应子（转录激活子和转录阻遏物）。 还描述了编码它们的核酸，以及使用它们调节基因表达的方法。 靶向转录效应子可以包含（i）缺少与靶标识别位点结合的核酸内切酶切割活性的大范围核酸酶DNA结合结构域; 和（ii）转录效应子结构域。

公开(公告)号：WO2022104062A1

公开(公告)日：2022-05-19

申请号：PCT/US2021/059146

申请日：2021-11-12

Applicant: PRECISION BIOSCIENCES, INC.

Inventor： OWENS, Gary ,  LAPE, Janel ,  SMITH, James, Jefferson ,  MORRIS, John ,  TURNER, Caitlin ,  LEWIS, Whitney ,  JANTZ, Derek

IPC: C12N9/22 ,  C07K14/47

Abstract: The present disclosure encompasses engineered meganucleases that bind and cleave recognition sequences within a dystrophin gene. The present disclosure also encompasses methods of using such engineered meganucleases to make genetically modified cells. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or polynucleotides encoding engineered meganucleases of the disclosure, and the use of such compositions for the modification of a dystrophin gene in a subject, or for treatment of Duchenne Muscular Dystrophy.

公开(公告)号：WO2020132659A1

公开(公告)日：2020-06-25

申请号：PCT/US2019/068186

申请日：2019-12-20

Applicant: PRECISION BIOSCIENCES, INC.

Inventor： DAVEY, Roshni ,  JANTZ, Derek ,  SMITH, James Jefferson ,  OWENS, Gary

IPC: C07K14/47 ,  A61K38/46 ,  A61K48/00 ,  C12N9/22 ,  C12N15/10 ,  C12N9/04

Abstract: Disclosed are engineered nucleases that bind and cleave a recognition sequence within a hydroxyacid oxidase 1 (HAO1 ) gene. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells. Further, the invention encompasses pharmaceutical compositions comprising engineered nuclease proteins or nucleic acids encoding engineered nucleases of the invention, and the use of such compositions for treatment of primary hyperoxaluria type I.

公开(公告)号：WO2019070856A1

公开(公告)日：2019-04-11

申请号：PCT/US2018/054164

申请日：2018-10-03

Applicant: PRECISION BIOSCIENCES, INC.

Inventor： JANTZ, Derek ,  SMITH, James, Jefferson ,  MACLEOD, Daniel, T.

IPC: C07K14/71 ,  C12N5/00

CPC classification number: C07K14/71 ,  C12N5/0087

Abstract: The present disclosure provides modified EGFR peptides useful in genetically-modified cells to allow for selection and enrichment of those cells expressing the modified EGFR peptide. For example, isolation of genetically-modified cells expressing a modified EGFR peptide can allow for selection of cells that co-express a chimeric antigen receptor or exogenous T cell receptor. In those instances wherein the genetically-modified cells present adverse effects when administered to a subject, the modified EGFR finds further use as a suicide gene upon administration of an anti-EGFR antibody, leading to depletion of the genetically-modified cells. Also disclosed herein are plasmids and viral vectors comprising a nucleic acid sequence encoding the modified EGFR peptides, and methods of administering compositions comprising the modified EGFR peptides to subjects in order to reduce the symptoms, progression, or occurrence of disease, such as cancer.

公开(公告)号：WO2019005957A1

公开(公告)日：2019-01-03

申请号：PCT/US2018/039740

申请日：2018-06-27

Applicant: PRECISION BIOSCIENCES, INC.

Inventor： JANTZ, Derek ,  SMITH, James, Jefferson ,  BEARD, Clayton

IPC: A61K39/00 ,  A61K35/17 ,  C12N5/0783

Abstract: The present invention provides a genetically-modified T cell comprising in its genome a modified human T cell receptor alpha gene. The modified T cell receptor alpha gene comprises an exogenous sequence of interest inserted into an intron within the T cell receptor alpha gene that is positioned 5' upstream of TRAC exon 1. The exogenous sequence of interest can comprise an exogenous splice acceptor site and/or a poly A signal, which disrupts expression of the T cell receptor alpha subunit. The sequence of interest can also include a coding sequence for a polypeptide, such as a chimeric antigen receptor. Additionally, the endogenous splice donor site and the endogenous splice acceptor site flanking the intron are unmodified and/or remain functional. The invention further provides compositions and methods for producing the genetically-modified cell, and populations of the cell, and methods for the treatment of a disease, such as cancer, using such cells.

公开(公告)号：WO2010009147A1

公开(公告)日：2010-01-21

申请号：PCT/US2009/050566

申请日：2009-07-14

Applicant: PRECISION BIOSCIENCES, INC. ,  JANTZ, Derek ,  SMITH, James, Jefferson

Inventor： JANTZ, Derek ,  SMITH, James, Jefferson

IPC: C12N9/22 ,  C12N5/10

CPC classification number: C12Q1/6811 ,  C12N9/22 ,  G06Q99/00

Abstract: Methods of cleaving double-stranded DNA that can be recognized and cleaved by a rationally-designed, I-Crel-derived meganuclease are provided. Also provided are recombinant nucleic acids, cells, and organisms containing such recombinant nucleic acids, as well as cells and organisms produced using such meganucleases. Also provided are methods of conducting a custom-designed, I-Crel-derived meganuclease business.

Abstract translation: 提供了可以通过合理设计的I-CreI衍生的大范围核酸酶识别和切割的双链DNA的切割方法。 还提供了含有这种重组核酸的重组核酸，细胞和生物，以及使用这种大范围核酸酶产生的细胞和生物体。 还提供了进行定制设计的I-Crel衍生的大范围核酸酶业务的方法。

公开(公告)号：WO2022226316A1

公开(公告)日：2022-10-27

申请号：PCT/US2022/025965

申请日：2022-04-22

Applicant: PRECISION BIOSCIENCES, INC. ,  NORTH CAROLINA STATE UNIVERSITY

Inventor： DEWEY, Ralph ,  JANTZ, Derek ,  SMITH, James Jefferson ,  TOMBERLIN, Ginger H. ,  MORRIS, John ,  MATTHIADIS, Anna ,  SHOOP, Wendy

IPC: C12N9/22 ,  C12N15/82

Abstract: Disclosed herein are recombinant meganucleases engineered to bind and cleave a recognition sequence in the mitochondrial DNA (mtDNA) of a eukaryotic cell, such as a plant cell. The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.