Haplotyping by CRISPR-mediated DNA circularization (CRISPR-hapC) broadens allele-specific gene editing

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Standard

Haplotyping by CRISPR-mediated DNA circularization (CRISPR-hapC) broadens allele-specific gene editing. / Yu, Jiaying; Xiang, Xi; Huang, Jinrong; Liang, Xue; Pan, Xiaoguang; Dong, Zhanying; Petersen, Trine Skov; Qu, Kunli; Yang, Ling; Zhao, Xiaoying; Li, Siyuan; Zheng, Tianyu; Xu, Zhe; Liu, Chengxun; Han, Peng; Xu, Fengping; Yang, Huanming; Liu, Xin; Zhang, Xiuqing; Bolund, Lars; Luo, Yonglun; Lin, Lin.

I: Nucleic Acids Research, Bind 48, Nr. 5, e25, 2020.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Yu, J, Xiang, X, Huang, J, Liang, X, Pan, X, Dong, Z, Petersen, TS, Qu, K, Yang, L, Zhao, X, Li, S, Zheng, T, Xu, Z, Liu, C, Han, P, Xu, F, Yang, H, Liu, X, Zhang, X, Bolund, L, Luo, Y & Lin, L 2020, 'Haplotyping by CRISPR-mediated DNA circularization (CRISPR-hapC) broadens allele-specific gene editing', Nucleic Acids Research, bind 48, nr. 5, e25. https://doi.org/10.1093/nar/gkz1233

APA

Yu, J., Xiang, X., Huang, J., Liang, X., Pan, X., Dong, Z., Petersen, T. S., Qu, K., Yang, L., Zhao, X., Li, S., Zheng, T., Xu, Z., Liu, C., Han, P., Xu, F., Yang, H., Liu, X., Zhang, X., ... Lin, L. (2020). Haplotyping by CRISPR-mediated DNA circularization (CRISPR-hapC) broadens allele-specific gene editing. Nucleic Acids Research, 48(5), [e25]. https://doi.org/10.1093/nar/gkz1233

Vancouver

Yu J, Xiang X, Huang J, Liang X, Pan X, Dong Z o.a. Haplotyping by CRISPR-mediated DNA circularization (CRISPR-hapC) broadens allele-specific gene editing. Nucleic Acids Research. 2020;48(5). e25. https://doi.org/10.1093/nar/gkz1233

Author

Yu, Jiaying ; Xiang, Xi ; Huang, Jinrong ; Liang, Xue ; Pan, Xiaoguang ; Dong, Zhanying ; Petersen, Trine Skov ; Qu, Kunli ; Yang, Ling ; Zhao, Xiaoying ; Li, Siyuan ; Zheng, Tianyu ; Xu, Zhe ; Liu, Chengxun ; Han, Peng ; Xu, Fengping ; Yang, Huanming ; Liu, Xin ; Zhang, Xiuqing ; Bolund, Lars ; Luo, Yonglun ; Lin, Lin. / Haplotyping by CRISPR-mediated DNA circularization (CRISPR-hapC) broadens allele-specific gene editing. I: Nucleic Acids Research. 2020 ; Bind 48, Nr. 5.

Bibtex

@article{467adfa4bcda4a1cb212a65e8939a0c5,
title = "Haplotyping by CRISPR-mediated DNA circularization (CRISPR-hapC) broadens allele-specific gene editing",
abstract = "Allele-specific protospacer adjacent motif (asPAM)-positioning SNPs and CRISPRs are valuable resources for gene therapy of dominant disorders. However, one technical hurdle is to identify the haplotype comprising the disease-causing allele and the distal asPAM SNPs. Here, we describe a novel CRISPR-based method (CRISPR-hapC) for haplotyping. Based on the generation (with a pair of CRISPRs) of extrachromosomal circular DNA in cells, the CRISPR-hapC can map haplotypes from a few hundred bases to over 200 Mb. To streamline and demonstrate the applicability of the CRISPR-hapC and asPAM CRISPR for allele-specific gene editing, we reanalyzed the 1000 human pan-genome and generated a high frequency asPAM SNP and CRISPR database (www.crispratlas.com/knockout) for four CRISPR systems (SaCas9, SpCas9, xCas9 and Cas12a). Using the huntingtin (HTT) CAG expansion and transthyretin (TTR) exon 2 mutation as examples, we showed that the asPAM CRISPRs can specifically discriminate active and dead PAMs for all 23 loci tested. Combination of the CRISPR-hapC and asPAM CRISPRs further demonstrated the capability for achieving highly accurate and haplotype-specific deletion of the HTT CAG expansion allele and TTR exon 2 mutation in human cells. Taken together, our study provides a new approach and an important resource for genome research and allele-specific (haplotype-specific) gene therapy.",
author = "Jiaying Yu and Xi Xiang and Jinrong Huang and Xue Liang and Xiaoguang Pan and Zhanying Dong and Petersen, {Trine Skov} and Kunli Qu and Ling Yang and Xiaoying Zhao and Siyuan Li and Tianyu Zheng and Zhe Xu and Chengxun Liu and Peng Han and Fengping Xu and Huanming Yang and Xin Liu and Xiuqing Zhang and Lars Bolund and Yonglun Luo and Lin Lin",
year = "2020",
doi = "10.1093/nar/gkz1233",
language = "English",
volume = "48",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Haplotyping by CRISPR-mediated DNA circularization (CRISPR-hapC) broadens allele-specific gene editing

AU - Yu, Jiaying

AU - Xiang, Xi

AU - Huang, Jinrong

AU - Liang, Xue

AU - Pan, Xiaoguang

AU - Dong, Zhanying

AU - Petersen, Trine Skov

AU - Qu, Kunli

AU - Yang, Ling

AU - Zhao, Xiaoying

AU - Li, Siyuan

AU - Zheng, Tianyu

AU - Xu, Zhe

AU - Liu, Chengxun

AU - Han, Peng

AU - Xu, Fengping

AU - Yang, Huanming

AU - Liu, Xin

AU - Zhang, Xiuqing

AU - Bolund, Lars

AU - Luo, Yonglun

AU - Lin, Lin

PY - 2020

Y1 - 2020

N2 - Allele-specific protospacer adjacent motif (asPAM)-positioning SNPs and CRISPRs are valuable resources for gene therapy of dominant disorders. However, one technical hurdle is to identify the haplotype comprising the disease-causing allele and the distal asPAM SNPs. Here, we describe a novel CRISPR-based method (CRISPR-hapC) for haplotyping. Based on the generation (with a pair of CRISPRs) of extrachromosomal circular DNA in cells, the CRISPR-hapC can map haplotypes from a few hundred bases to over 200 Mb. To streamline and demonstrate the applicability of the CRISPR-hapC and asPAM CRISPR for allele-specific gene editing, we reanalyzed the 1000 human pan-genome and generated a high frequency asPAM SNP and CRISPR database (www.crispratlas.com/knockout) for four CRISPR systems (SaCas9, SpCas9, xCas9 and Cas12a). Using the huntingtin (HTT) CAG expansion and transthyretin (TTR) exon 2 mutation as examples, we showed that the asPAM CRISPRs can specifically discriminate active and dead PAMs for all 23 loci tested. Combination of the CRISPR-hapC and asPAM CRISPRs further demonstrated the capability for achieving highly accurate and haplotype-specific deletion of the HTT CAG expansion allele and TTR exon 2 mutation in human cells. Taken together, our study provides a new approach and an important resource for genome research and allele-specific (haplotype-specific) gene therapy.

AB - Allele-specific protospacer adjacent motif (asPAM)-positioning SNPs and CRISPRs are valuable resources for gene therapy of dominant disorders. However, one technical hurdle is to identify the haplotype comprising the disease-causing allele and the distal asPAM SNPs. Here, we describe a novel CRISPR-based method (CRISPR-hapC) for haplotyping. Based on the generation (with a pair of CRISPRs) of extrachromosomal circular DNA in cells, the CRISPR-hapC can map haplotypes from a few hundred bases to over 200 Mb. To streamline and demonstrate the applicability of the CRISPR-hapC and asPAM CRISPR for allele-specific gene editing, we reanalyzed the 1000 human pan-genome and generated a high frequency asPAM SNP and CRISPR database (www.crispratlas.com/knockout) for four CRISPR systems (SaCas9, SpCas9, xCas9 and Cas12a). Using the huntingtin (HTT) CAG expansion and transthyretin (TTR) exon 2 mutation as examples, we showed that the asPAM CRISPRs can specifically discriminate active and dead PAMs for all 23 loci tested. Combination of the CRISPR-hapC and asPAM CRISPRs further demonstrated the capability for achieving highly accurate and haplotype-specific deletion of the HTT CAG expansion allele and TTR exon 2 mutation in human cells. Taken together, our study provides a new approach and an important resource for genome research and allele-specific (haplotype-specific) gene therapy.

U2 - 10.1093/nar/gkz1233

DO - 10.1093/nar/gkz1233

M3 - Journal article

C2 - 31943080

AN - SCOPUS:85081074686

VL - 48

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 5

M1 - e25

ER -

ID: 237997037