Title:
METHOD FOR REPAIRING HBA2 GENE MUTATIONS BY SINGLE BASE EDITING AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/193616
Kind Code:
A1
Abstract:
A method for repairing HBA2 gene mutations by single base editing and use thereof, belonging to the technical field of gene editing. The method comprises the following steps: contacting a single base editor and gRNA with an HBA gene sequence to be edited and repaired, deaminating the codon target cytosine base at CD142 in the HBA gene sequence, and converting the cytosine into thymine. According to the method, pathogenic mutation sites can be accurately edited without generating double-strand breaks and affecting chromatin conformation and genome stability, without generating random insertions of large-fragment genes into genomes, which have a low influence on cancer gene activation or tumor-inhibiting gene inactivation, and without generating random insertions/deletions at other sites of a genome. The expression of the repaired target gene is regulated by all regulatory elements of natural HBA2; therefore, the method is very safe and can also better balance the expression of α/β globin.
Inventors:
LIANG JUNBIN (CN)
XU HUI (CN)
YE LU (CN)
LIN SIMIAO (CN)
XU HUI (CN)
YE LU (CN)
LIN SIMIAO (CN)
Application Number:
PCT/CN2023/083728
Publication Date:
October 12, 2023
Filing Date:
March 24, 2023
Export Citation:
Assignee:
GUANGZHOU REFORGENE MEDICINE CO LTD (CN)
International Classes:
C12N15/90; C12N5/10; C12N9/22
Domestic Patent References:
| WO2021097350A1 | 2021-05-20 |
Foreign References:
| CN108165581A | 2018-06-15 | |||
| CN109136272A | 2019-01-04 | |||
| CN113453696A | 2021-09-28 | |||
| CN108823202A | 2018-11-16 | |||
| CN109294994A | 2019-02-01 |
Other References:
WU, Y.X. ET AL.: "Highly Efficient Therapeutic Gene Editing of Human Hematopoietic Stem Cells", NATURE MEDICINE, vol. 25, 25 March 2019 (2019-03-25), XP036778187, DOI: 10.1038/s41591-019-0401-y
XIE, Y.J. ET AL.: "CRISPR/Cas9 Gene Correction of HbH-CS Thalassemia-Induced Pluripotent Stem Cells", ANNALS OF HEMATOLOGY, vol. 98, 9 September 2019 (2019-09-09), XP036961706, DOI: 10.1007/s00277-019-03763-2
PAVANI GIULIA, FABIANO ANNA, LAURENT MARINE, AMOR FATIMA, CANTELLI ERIKA, CHALUMEAU ANNE, MAULE GIULIA, TACHTSIDI ALEXANDRA, CONCO: "Correction of β-thalassemia by CRISPR/Cas9 editing of the α-globin locus in human hematopoietic stem cells", BLOOD ADVANCES, vol. 5, no. 5, 9 March 2021 (2021-03-09), pages 1137 - 1153, XP055900185, ISSN: 2473-9529, DOI: 10.1182/bloodadvances.2020001996
BAO LI WEN, ZHOU YI YE, ZENG FAN YI: "Advances in gene therapy for β-thalassemia and hemophilia based on the CRISPR/Cas9 technology", HEREDITAS, ZHONGGUO YICHUAN XUEHUI KEXUE, BEJING, CN, vol. 42, no. 10, 20 October 2020 (2020-10-20), CN , pages 949 - 964, XP093097200, ISSN: 0253-9772, DOI: 10.16288/j.yczz.20-110
XIE, Y.J. ET AL.: "CRISPR/Cas9 Gene Correction of HbH-CS Thalassemia-Induced Pluripotent Stem Cells", ANNALS OF HEMATOLOGY, vol. 98, 9 September 2019 (2019-09-09), XP036961706, DOI: 10.1007/s00277-019-03763-2
PAVANI GIULIA, FABIANO ANNA, LAURENT MARINE, AMOR FATIMA, CANTELLI ERIKA, CHALUMEAU ANNE, MAULE GIULIA, TACHTSIDI ALEXANDRA, CONCO: "Correction of β-thalassemia by CRISPR/Cas9 editing of the α-globin locus in human hematopoietic stem cells", BLOOD ADVANCES, vol. 5, no. 5, 9 March 2021 (2021-03-09), pages 1137 - 1153, XP055900185, ISSN: 2473-9529, DOI: 10.1182/bloodadvances.2020001996
BAO LI WEN, ZHOU YI YE, ZENG FAN YI: "Advances in gene therapy for β-thalassemia and hemophilia based on the CRISPR/Cas9 technology", HEREDITAS, ZHONGGUO YICHUAN XUEHUI KEXUE, BEJING, CN, vol. 42, no. 10, 20 October 2020 (2020-10-20), CN , pages 949 - 964, XP093097200, ISSN: 0253-9772, DOI: 10.16288/j.yczz.20-110
Attorney, Agent or Firm:
GUANGZHOU SINO PATENT & TRADEMARK AGENT CO., LTD. et al. (CN)
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