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Guanglei Li
Guangzhou Medical University
9Publications
4H-index
122Citations
Publications 11
Newest
#1Yin Liu (WHU: Wuhan University)H-Index: 1
#2Guanglei Li (ShanghaiTech University)H-Index: 4
Last.Yong-ChangWei (WHU: Wuhan University)H-Index: 11
view all 11 authors...
Base editors (BEs) are widely used in precise gene editing due to their simplicity and versatility. However, their efficiencies are hindered by various obstacles. Considering the chromatin microenvironment as a possible obstacle, here, we demonstrate a further development of the proxy-clustered regularly interspaced short palindromic repeats strategy, termed Proxy-BE, to increase gene editing efficiency. Specifically, a nuclease-dead Cas9 (dCas9) was bound to the sequence about 20-30 base pair a...
Source
#1Xinjie Wang (SCNU: South China Normal University)H-Index: 1
#2Zhiwei Liu (Soochow University (Suzhou))
Last.Xiaodong Ma (SCNU: South China Normal University)H-Index: 1
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Abstract Traditional CRISPR/Cas9-based gene knockouts are generated by introducing DNA double-strand breaks (DSBs), but this may cause excessive DNA damage or cell death. CRISPR-based cytosine base editors (CBEs) and adenine base editors (ABEs) can facilitate C-to-T or A-to-G exchanges, respectively, without DSBs. CBEs have been employed in a gene knockout strategy: CRISPR-STOP or i-STOP changes single nucleotides to induce in-frame stop codons. However, this strategy is not applicable for some ...
1 CitationsSource
#1Guanglei Li (Guangzhou Medical University)H-Index: 4
#2Xinyi Liu (JNU: Jinan University)H-Index: 1
Last.Jianqiao Liu (Guangzhou Medical University)H-Index: 2
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Base editing systems show their power in modeling and correcting the pathogenic mutations of genetic diseases. Previous studies have already demonstrated the editing efficiency of BE3-mediated C-to-T conversion in human embryos. However, the precision and efficiency of a recently developed adenine base editor (ABE), which converts A-to-G editing in human embryos, remain to be addressed. Here we selected reported pathogenic mutations to characterize the ABE in human tripronuclear embryos. We foun...
1 CitationsSource
#1Xinyi Liu (JNU: Jinan University)H-Index: 1
#2Guanglei Li (Guangzhou Medical University)H-Index: 4
Last.Xingxu Huang (ShanghaiTech University)H-Index: 22
view all 9 authors...
The development of CRISPR/Cas9-mediated base editors (BEs) provided a versatile tool for precise genome editing. The recently developed xCas9-derived base editors (xBEs) that recognize the NG PAM substantially expand the targeting scope in the genome, while their editing efficiency needs to be improved. Here, we described an improved version of xBEs by fusing the BPNLS and Gam to the N terminus of xBEs (BPNLS-Gam-xBE3 and BPNLS-xABE), and this version of base editor displayed higher targeting ef...
1 CitationsSource
#1Shisheng Huang (CAS: Chinese Academy of Sciences)H-Index: 3
#2Zhaodi Liao (CAS: Chinese Academy of Sciences)H-Index: 1
Last.Xingxu Huang (CAS: Chinese Academy of Sciences)H-Index: 22
view all 12 authors...
RNA splicing is related to many human diseases; however, lack of efficient genetic approaches to modulate splicing has prevented us from dissecting their functions in human diseases. Recently developed base editors (BEs) offer a new strategy to modulate RNA splicing by converting conservative splice sites, but it is limited by the editing precision and scope. To overcome the limitations of currently available BE-based tools, we combined SpCas9-NG with ABE-max to generate a new BE, ABEmax-NG. We ...
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#1Jianan Li (CAS: Chinese Academy of Sciences)H-Index: 8
#2Zhen Liu (CAS: Chinese Academy of Sciences)H-Index: 12
Last.Xingxu Huang (CAS: Chinese Academy of Sciences)H-Index: 22
view all 14 authors...
2 CitationsSource
#1Zhen Liu (CAS: Chinese Academy of Sciences)H-Index: 12
#2Zongyang Lu (ShanghaiTech University)H-Index: 3
Last.Xingxu Huang (CAS: Chinese Academy of Sciences)H-Index: 22
view all 13 authors...
A recently developed adenine base editor (ABE) efficiently converts A to G and is potentially useful for clinical applications. However, its precision and efficiency in vivo remains to be addressed. Here we achieve A-to-G conversion in vivo at frequencies up to 100% by microinjection of ABE mRNA together with sgRNAs. We then generate mouse models harboring clinically relevant mutations at Ar and Hoxd13, which recapitulates respective clinical defects. Furthermore, we achieve both C-to-T and A-to...
38 CitationsSource
#1Yanting Zeng (Guangzhou Medical University)H-Index: 2
#2Jianan Li (ShanghaiTech University)H-Index: 8
Last.Xingxu Huang (CAS: Chinese Academy of Sciences)H-Index: 22
view all 10 authors...
There are urgent demands for efficient treatment of heritable genetic diseases. The base editing technology has displayed its efficiency and precision in base substitution in human embryos, providing a potential early-stage treatment for genetic diseases. Taking advantage of this technology, we corrected a Marfan syndrome pathogenic mutation, FBN1T7498C. We first tested the feasibility in mutant cells, then successfully achieved genetic correction in heterozygous human embryos. The results showe...
24 CitationsSource
#1Guang Yang (ShanghaiTech University)H-Index: 20
#2Tianyu Zhu (Nanjing Medical University)H-Index: 1
Last.Xingxu Huang (ShanghaiTech University)H-Index: 22
view all 12 authors...
Although CRISPR/Cas9 has been widely used to generate knockout mice, two major limitations remain: the founders usually carry a mixture of genotypes, and mosaicism harboring multiple genotypes. Therefore, it takes a long time to get homozygous mutants. Recently developed base editing (BE) system, which introduces C-to-T conversion without double strand DNA cleavage, has been used to introduce artificial stop codons (i-STOP) to prematurely terminate translation, providing a cleaner strategy for g...
1 CitationsSource
#1Wen Jiang (Third Military Medical University)H-Index: 1
#2S. M. Feng (CAS: Chinese Academy of Sciences)H-Index: 4
Last.Xingxu Huang (ShanghaiTech University)H-Index: 22
view all 13 authors...
Base editor (BE), containing a cytidine deaminase and catalytically defective Cas9, has been widely used to perform base editing. However, the narrow editing window of BE limits its utility. Here, we developed a new editing technology named as base editor for programming larger C to U (T) scope (BE-PLUS) by fusing 10 copies of GCN4 peptide to nCas9(D10A) for recruiting scFv-APOBEC-UGI-GB1 to the target sites. The new system achieves base editing with a broadened window, resulting in an increased...
23 CitationsSource
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