公开(公告)号：US20240026342A1

公开(公告)日：2024-01-25

申请号：US18478861

申请日：2023-09-29

Applicant: ShanghaiTech University

Inventor： Jia Chen ,  Bei Yang ,  Li Yang ,  Xingxu Huang ,  Lijie Wang

IPC: C12N15/10 ,  C12N9/22 ,  C12N9/50 ,  C12N9/78 ,  C12N15/11

CPC classification number: C12N15/102 ,  C12N9/22 ,  C12N9/506 ,  C12N9/78 ,  C12N15/111 ,  C12N2310/20 ,  C07K2319/50 ,  C07K2319/85 ,  C12Y304/22044 ,  C12Y305/04004 ,  C12Y305/04005

Abstract: Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion protein may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

公开(公告)号：US20230094769A1

公开(公告)日：2023-03-30

申请号：US17862354

申请日：2022-07-11

Applicant: ShanghaiTech University

Inventor： Jia Chen ,  Bei Yang ,  Li Yang ,  Xingxu Huang ,  Lijie Wang

IPC: C12N15/10 ,  C12N9/22 ,  C12N9/50 ,  C12N9/78 ,  C12N15/11

Abstract: Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion protein may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

公开(公告)号：US11384353B2

公开(公告)日：2022-07-12

申请号：US17427040

申请日：2020-02-03

Applicant: ShanghaiTech University

Inventor： Jia Chen ,  Bei Yang ,  Li Yang ,  Xingxu Huang ,  Lijie Wang

IPC: C12N15/10 ,  C12N9/22 ,  C12N9/50 ,  C12N15/11 ,  C12N9/78

Abstract: Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion proteins may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitory domain, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

公开(公告)号：US11840685B2

公开(公告)日：2023-12-12

申请号：US17862354

申请日：2022-07-11

Applicant: ShanghaiTech University

Inventor： Jia Chen ,  Bei Yang ,  Li Yang ,  Xingxu Huang ,  Lijie Wang

IPC: C12N15/10 ,  C12N9/22 ,  C12N9/50 ,  C12N9/78 ,  C12N15/11

CPC classification number: C12N15/102 ,  C12N9/22 ,  C12N9/506 ,  C12N9/78 ,  C12N15/111 ,  C07K2319/50 ,  C07K2319/85 ,  C12N2310/20 ,  C12Y304/22044 ,  C12Y305/04004 ,  C12Y305/04005

Abstract: Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion protein may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

公开(公告)号：US20210163913A1

公开(公告)日：2021-06-03

申请号：US16770572

申请日：2019-02-22

Applicant: ShanghaiTech University

Inventor： Jia Chen ,  Li Yang ,  Xingxu Huang ,  Bei Yang ,  Xiao Wang ,  Jianan Li

IPC: C12N9/78 ,  C12N9/22 ,  C12N15/90 ,  C12N15/11

Abstract: Provided are fusion proteins that include an apolipoprotein B mRNA editing enzyme catalytic subunit 3A (APOBEC3A) and a clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) protein, optionally further with uracil glycosylase inhibitor (UGI). Such a fusion protein is able to conduct base editing in DNA by deaminating cytosine to uracil, even when the cytosine is in a GpC context or is methylated.

公开(公告)号：US12203077B2

公开(公告)日：2025-01-21

申请号：US16640337

申请日：2018-08-28

Applicant: ShanghaiTech University

Inventor： Jia Chen ,  Xingxu Huang ,  Li Yang ,  Bei Yang ,  Xiaosa Li ,  Ying Wang ,  Yajing Liu

IPC: C12N9/22 ,  C07K14/32 ,  C12N9/78 ,  C12N15/10 ,  C12N15/79

Abstract: Provided are base editors containing a cytidine and a catalytically inactive version of Lachnospiraceae bacterium Cpf1 (LbCpf1). The new base editors have greatly improved editing efficiency and fidelity as compared to Cas9-based base editors, and have different editing windows.

公开(公告)号：US20240117335A1

公开(公告)日：2024-04-11

申请号：US18525555

申请日：2023-11-30

Applicant: ShanghaiTech University

Inventor： Jia CHEN ,  Li Yang ,  Xingxu Huang ,  Bei Yang ,  Xiao Wang ,  Jianan Li

IPC: C12N9/78 ,  C12N9/22 ,  C12N15/11 ,  C12N15/90

CPC classification number: C12N9/78 ,  C12N9/22 ,  C12N15/11 ,  C12N15/907 ,  C12Y305/04 ,  C07K2319/00 ,  C12N2310/20 ,  C12N2800/80

Abstract: Provided are fusion proteins that include an apolipoprotein B mRNA editing enzyme catalytic subunit 3A (APOBEC3A) and a clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) protein, optionally further with uracil glycosylase inhibitor (UGI). Such a fusion protein is able to conduct base editing in DNA by deaminating cytosine to uracil, even when the cytosine is in a GpC context or is methylated.

公开(公告)号：US12134771B2

公开(公告)日：2024-11-05

申请号：US18150778

申请日：2023-01-05

Applicant: ShanghaiTech University

Inventor： Yajing Liu ,  Shisheng Huang ,  Xingxu Huang

IPC: C12N15/62 ,  C07K14/775 ,  C12N9/22

Abstract: A fusion protein which may comprise a first nCas9 fragment, a chimeric insertion fragment, a second nCas9 fragment and two UGI fragments from N-terminus to C-terminus, wherein the chimeric insertion fragment is selected from APOBEC1 fragment or APOBEC3A fragment for cytosine deamination at the target site. The fusion protein may comprise a first nCas9 fragment, a chimeric insertion fragment and a second nCas9 fragment from N-terminus to C-terminus, wherein the chimeric insertion fragment is TadA-TadA* for cytosine deamination at the target site. The present disclosure provides a novel base editing tool that is compatible with insertion of various deaminases on the chimeric sites of nCas9. Compared with nCas9 terminal fusion base editor, the base editing tool of the present invention significantly reduce off-targeting on both DNA and RNA, while maintaining specific targeted base editing efficiency, with higher specificity and favorable industrialization prospects.

公开(公告)号：US12123006B2

公开(公告)日：2024-10-22

申请号：US17323603

申请日：2021-05-18

Applicant: SHANGHAITECH UNIVERSITY

Inventor： Yajing Liu ,  Shisheng Huang ,  Xingxu Huang

IPC: C12N15/62 ,  C07K14/775 ,  C12N9/22

CPC classification number: C12N15/625 ,  C07K14/775 ,  C12N9/22 ,  C07K2319/09

Abstract: The present disclosure relates to the field of biotechnology, in particular to a base editing tool and use thereof. The present disclosure provides a fusion protein comprising a first nCas9 fragment, a chimeric insertion fragment, a second nCas9 fragment and two UGI fragments from N-terminus to C-terminus, wherein the chimeric insertion fragment is selected from APOBEC1 fragment or APOBEC3A fragment. The present disclosure provides a novel base editing tool that is compatible with insertion of various deaminases on the chimeric sites of nCas9. Compared with nCas9 terminal fusion base editor, the base editing tool of the present invention significantly reduce of off-targeting on both DNA and RNA, while maintaining specific targeted base editing efficiency, with higher specificity and favorable industrialization prospects.

公开(公告)号：US11884947B2

公开(公告)日：2024-01-30

申请号：US16770572

申请日：2019-02-22

Applicant: ShanghaiTech University

Inventor： Jia Chen ,  Li Yang ,  Xingxu Huang ,  Bei Yang ,  Xiao Wang ,  Jianan Li

IPC: C12N9/78 ,  C12N9/22 ,  C12N15/11 ,  C12N15/90 ,  C12N15/01

CPC classification number: C12N9/78 ,  C12N9/22 ,  C12N15/01 ,  C12N15/907 ,  C12Y305/04 ,  C07K2319/00 ,  C12N2310/20 ,  C12N2800/80

Abstract: Provided are fusion proteins that include an apolipoprotein B mRNA editing enzyme catalytic subunit 3A (APOBEC3A) and a clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) protein, optionally further with uracil glycosylase inhibitor (UGI). Such a fusion protein is able to conduct base editing in DNA by deaminating cytosine to uracil, even when the cytosine is in a GpC context or is methylated.