IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31927-8.html
   My bibliography  Save this article

Multiplex base editing to convert TAG into TAA codons in the human genome

Author

Listed:
  • Yuting Chen

    (Harvard Medical School
    Wyss Institute for Biologically Inspired Engineering
    Chinese Academy of Sciences)

  • Eriona Hysolli

    (Harvard Medical School
    Wyss Institute for Biologically Inspired Engineering)

  • Anlu Chen

    (Harvard Medical School)

  • Stephen Casper

    (Harvard Medical School)

  • Songlei Liu

    (Harvard Medical School
    Wyss Institute for Biologically Inspired Engineering)

  • Kevin Yang

    (Harvard Medical School)

  • Chenli Liu

    (Chinese Academy of Sciences)

  • George Church

    (Harvard Medical School
    Wyss Institute for Biologically Inspired Engineering)

Abstract

Whole-genome recoding has been shown to enable nonstandard amino acids, biocontainment and viral resistance in bacteria. Here we take the first steps to extend this to human cells demonstrating exceptional base editing to convert TAG to TAA for 33 essential genes via a single transfection, and examine base-editing genome-wide (observing ~40 C-to-T off-target events in essential gene exons). We also introduce GRIT, a computational tool for recoding. This demonstrates the feasibility of recoding, and highly multiplex editing in mammalian cells.

Suggested Citation

  • Yuting Chen & Eriona Hysolli & Anlu Chen & Stephen Casper & Songlei Liu & Kevin Yang & Chenli Liu & George Church, 2022. "Multiplex base editing to convert TAG into TAA codons in the human genome," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31927-8
    DOI: 10.1038/s41467-022-31927-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31927-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-31927-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Nicholas S. McCarty & Alicia E. Graham & Lucie Studená & Rodrigo Ledesma-Amaro, 2020. "Multiplexed CRISPR technologies for gene editing and transcriptional regulation," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. Alexis J. Rovner & Adrian D. Haimovich & Spencer R. Katz & Zhe Li & Michael W. Grome & Brandon M. Gassaway & Miriam Amiram & Jaymin R. Patel & Ryan R. Gallagher & Jesse Rinehart & Farren J. Isaacs, 2015. "Correction: Corrigendum: Recoded organisms engineered to depend on synthetic amino acids," Nature, Nature, vol. 527(7577), pages 264-264, November.
    3. Julius Fredens & Kaihang Wang & Daniel Torre & Louise F. H. Funke & Wesley E. Robertson & Yonka Christova & Tiongsun Chia & Wolfgang H. Schmied & Daniel L. Dunkelmann & Václav Beránek & Chayasith Utta, 2019. "Total synthesis of Escherichia coli with a recoded genome," Nature, Nature, vol. 569(7757), pages 514-518, May.
    4. Yajing Liu & Changyang Zhou & Shisheng Huang & Lu Dang & Yu Wei & Jun He & Yingsi Zhou & Shaoshuai Mao & Wanyu Tao & Yu Zhang & Hui Yang & Xingxu Huang & Tian Chi, 2020. "A Cas-embedding strategy for minimizing off-target effects of DNA base editors," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    5. Beverly Y. Mok & Marcos H. de Moraes & Jun Zeng & Dustin E. Bosch & Anna V. Kotrys & Aditya Raguram & FoSheng Hsu & Matthew C. Radey & S. Brook Peterson & Vamsi K. Mootha & Joseph D. Mougous & David R, 2020. "A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing," Nature, Nature, vol. 583(7817), pages 631-637, July.
    6. Jessica S. Dymond & Sarah M. Richardson & Candice E. Coombes & Timothy Babatz & Héloïse Muller & Narayana Annaluru & William J. Blake & Joy W. Schwerzmann & Junbiao Dai & Derek L. Lindstrom & Annabel , 2011. "Synthetic chromosome arms function in yeast and generate phenotypic diversity by design," Nature, Nature, vol. 477(7365), pages 471-476, September.
    7. Krishanu Saha & Erik J. Sontheimer & P. J. Brooks & Melinda R. Dwinell & Charles A. Gersbach & David R. Liu & Stephen A. Murray & Shengdar Q. Tsai & Ross C. Wilson & Daniel G. Anderson & Aravind Asoka, 2021. "The NIH Somatic Cell Genome Editing program," Nature, Nature, vol. 592(7853), pages 195-204, April.
    8. Andrew V. Anzalone & Peyton B. Randolph & Jessie R. Davis & Alexander A. Sousa & Luke W. Koblan & Jonathan M. Levy & Peter J. Chen & Christopher Wilson & Gregory A. Newby & Aditya Raguram & David R. L, 2019. "Search-and-replace genome editing without double-strand breaks or donor DNA," Nature, Nature, vol. 576(7785), pages 149-157, December.
    9. Alexis C. Komor & Yongjoo B. Kim & Michael S. Packer & John A. Zuris & David R. Liu, 2016. "Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage," Nature, Nature, vol. 533(7603), pages 420-424, May.
    10. Alexis J. Rovner & Adrian D. Haimovich & Spencer R. Katz & Zhe Li & Michael W. Grome & Brandon M. Gassaway & Miriam Amiram & Jaymin R. Patel & Ryan R. Gallagher & Jesse Rinehart & Farren J. Isaacs, 2015. "Recoded organisms engineered to depend on synthetic amino acids," Nature, Nature, vol. 518(7537), pages 89-93, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jianli Tao & Daniel E. Bauer & Roberto Chiarle, 2023. "Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Huawei Tong & Haoqiang Wang & Xuchen Wang & Nana Liu & Guoling Li & Danni Wu & Yun Li & Ming Jin & Hengbin Li & Yinghui Wei & Tong Li & Yuan Yuan & Linyu Shi & Xuan Yao & Yingsi Zhou & Hui Yang, 2024. "Development of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Qichen Yuan & Hongzhi Zeng & Tyler C. Daniel & Qingzhuo Liu & Yongjie Yang & Emmanuel C. Osikpa & Qiaochu Yang & Advaith Peddi & Liliana M. Abramson & Boyang Zhang & Yong Xu & Xue Gao, 2024. "Orthogonal and multiplexable genetic perturbations with an engineered prime editor and a diverse RNA array," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Friedrich Fauser & Bhakti N. Kadam & Sebastian Arangundy-Franklin & Jessica E. Davis & Vishvesha Vaidya & Nicola J. Schmidt & Garrett Lew & Danny F. Xia & Rakshaa Mureli & Colman Ng & Yuanyue Zhou & N, 2024. "Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Tiantian Chang & Weichao Ding & Shirui Yan & Yun Wang & Haoling Zhang & Yu Zhang & Zhi Ping & Huiming Zhang & Yijian Huang & Jiahui Zhang & Dan Wang & Wenwei Zhang & Xun Xu & Yue Shen & Xian Fu, 2023. "A robust yeast biocontainment system with two-layered regulation switch dependent on unnatural amino acid," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Qichen Yuan & Xue Gao, 2022. "Multiplex base- and prime-editing with drive-and-process CRISPR arrays," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Peter N. Ciaccia & Zhuobin Liang & Anabel Y. Schweitzer & Eli Metzner & Farren J. Isaacs, 2024. "Enhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    8. Xiaoguang Pan & Kunli Qu & Hao Yuan & Xi Xiang & Christian Anthon & Liubov Pashkova & Xue Liang & Peng Han & Giulia I. Corsi & Fengping Xu & Ping Liu & Jiayan Zhong & Yan Zhou & Tao Ma & Hui Jiang & J, 2022. "Massively targeted evaluation of therapeutic CRISPR off-targets in cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Qiwen Su-Tobon & Jiayi Fan & Michael Goldstein & Kevin Feeney & Hongyuan Ren & Patrick Autissier & Peiyi Wang & Yingzi Huang & Udayan Mohanty & Jia Niu, 2025. "CRISPR-Hybrid: A CRISPR-Mediated Intracellular Directed Evolution Platform for RNA Aptamers," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    10. Ronghao Chen & Yu Cao & Yajing Liu & Dongdong Zhao & Ju Li & Zhihui Cheng & Changhao Bi & Xueli Zhang, 2023. "Enhancement of a prime editing system via optimal recruitment of the pioneer transcription factor P65," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    11. Xiangfeng Kong & Hainan Zhang & Guoling Li & Zikang Wang & Xuqiang Kong & Lecong Wang & Mingxing Xue & Weihong Zhang & Yao Wang & Jiajia Lin & Jingxing Zhou & Xiaowen Shen & Yinghui Wei & Na Zhong & W, 2023. "Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Nathan Bamidele & Han Zhang & Xiaolong Dong & Haoyang Cheng & Nicholas Gaston & Hailey Feinzig & Hanbing Cao & Karen Kelly & Jonathan K. Watts & Jun Xie & Guangping Gao & Erik J. Sontheimer, 2024. "Domain-inlaid Nme2Cas9 adenine base editors with improved activity and targeting scope," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    13. Emily Zhang & Monica E. Neugebauer & Nicholas A. Krasnow & David R. Liu, 2024. "Phage-assisted evolution of highly active cytosine base editors with enhanced selectivity and minimal sequence context preference," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    14. You-Jeong Kim & Dayoung Yun & Jungjoon K. Lee & Cheulhee Jung & Aram J. Chung, 2024. "Highly efficient CRISPR-mediated genome editing through microfluidic droplet cell mechanoporation," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    15. Hongxia Zhao & Wenlong Ding & Jia Zang & Yang Yang & Chao Liu & Linzhen Hu & Yulin Chen & Guanglong Liu & Yu Fang & Ying Yuan & Shixian Lin, 2021. "Directed-evolution of translation system for efficient unnatural amino acids incorporation and generalizable synthetic auxotroph construction," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    16. Yi-Li Feng & Qian Liu & Ruo-Dan Chen & Si-Cheng Liu & Zhi-Cheng Huang & Kun-Ming Liu & Xiao-Ying Yang & An-Yong Xie, 2022. "DNA nicks induce mutational signatures associated with BRCA1 deficiency," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    17. Michael Kosicki & Felicity Allen & Frances Steward & Kärt Tomberg & Yangyang Pan & Allan Bradley, 2022. "Cas9-induced large deletions and small indels are controlled in a convergent fashion," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    18. Marion Rosello & Malo Serafini & Luca Mignani & Dario Finazzi & Carine Giovannangeli & Marina C. Mione & Jean-Paul Concordet & Filippo Del Bene, 2022. "Disease modeling by efficient genome editing using a near PAM-less base editor in vivo," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    19. Guoling Li & Xue Dong & Jiamin Luo & Tanglong Yuan & Tong Li & Guoli Zhao & Hainan Zhang & Jingxing Zhou & Zhenhai Zeng & Shuna Cui & Haoqiang Wang & Yin Wang & Yuyang Yu & Yuan Yuan & Erwei Zuo & Chu, 2024. "Engineering TadA ortholog-derived cytosine base editor without motif preference and adenosine activity limitation," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    20. Péter István Kulcsár & András Tálas & Zoltán Ligeti & Eszter Tóth & Zsófia Rakvács & Zsuzsa Bartos & Sarah Laura Krausz & Ágnes Welker & Vanessza Laura Végi & Krisztina Huszár & Ervin Welker, 2023. "A cleavage rule for selection of increased-fidelity SpCas9 variants with high efficiency and no detectable off-targets," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31927-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.