IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35580-z.html
   My bibliography  Save this article

Design of a self-driven probiotic-CRISPR/Cas9 nanosystem for sono-immunometabolic cancer therapy

Author

Listed:
  • Jifeng Yu

    (Fudan University)

  • Bangguo Zhou

    (Tongji University
    School of Clinical Medicine of Nanjing Medical University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Shen Zhang

    (Tongji University
    School of Clinical Medicine of Nanjing Medical University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Haohao Yin

    (Fudan University
    Tongji University
    School of Clinical Medicine of Nanjing Medical University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Liping Sun

    (Tongji University
    School of Clinical Medicine of Nanjing Medical University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Yinying Pu

    (Tongji University
    School of Clinical Medicine of Nanjing Medical University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Boyang Zhou

    (Fudan University)

  • Yikang Sun

    (Fudan University)

  • Xiaolong Li

    (Fudan University)

  • Yan Fang

    (Tongji University
    School of Clinical Medicine of Nanjing Medical University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Lifan Wang

    (Fudan University)

  • Chongke Zhao

    (Fudan University)

  • Dou Du

    (Tongji University
    School of Clinical Medicine of Nanjing Medical University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Yan Zhang

    (Tongji University
    School of Clinical Medicine of Nanjing Medical University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Huixiong Xu

    (Fudan University)

Abstract

Reprogramming the tumor immunosuppressive microenvironment is a promising strategy for improving tumor immunotherapy efficacy. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 system can be used to knockdown tumor immunosuppression-related genes. Therefore, here, a self-driven multifunctional delivery vector is constructed to efficiently deliver the CRISPR-Cas9 nanosystem for indoleamine 2,3-dioxygenase-1 (IDO1) knockdown in order to amplify immunogenic cell death (ICD) and then reverse tumor immunosuppression. Lactobacillus rhamnosus GG (LGG) is a self-driven safety probiotic that can penetrate the hypoxia tumor center, allowing efficient delivery of the CRISPR/Cas9 system to the tumor region. While LGG efficiently colonizes the tumor area, it also stimulates the organism to activate the immune system. The CRISPR/Cas9 nanosystem can generate abundant reactive oxygen species (ROS) under the ultrasound irradiation, resulting in ICD, while the produced ROS can induce endosomal/lysosomal rupture and then releasing Cas9/sgRNA to knock down the IDO1 gene to lift immunosuppression. The system generates immune responses that effectively attack tumor cells in mice, contributing to the inhibition of tumor re-challenge in vivo. In addition, this strategy provides an immunological memory effect which offers protection against lung metastasis.

Suggested Citation

  • Jifeng Yu & Bangguo Zhou & Shen Zhang & Haohao Yin & Liping Sun & Yinying Pu & Boyang Zhou & Yikang Sun & Xiaolong Li & Yan Fang & Lifan Wang & Chongke Zhao & Dou Du & Yan Zhang & Huixiong Xu, 2022. "Design of a self-driven probiotic-CRISPR/Cas9 nanosystem for sono-immunometabolic cancer therapy," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35580-z
    DOI: 10.1038/s41467-022-35580-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35580-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-35580-z?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. Silvana Konermann & Mark D. Brigham & Alexandro E. Trevino & Julia Joung & Omar O. Abudayyeh & Clea Barcena & Patrick D. Hsu & Naomi Habib & Jonathan S. Gootenberg & Hiroshi Nishimasu & Osamu Nureki &, 2015. "Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex," Nature, Nature, vol. 517(7536), pages 583-588, January.
    2. Luigi Naldini, 2015. "Gene therapy returns to centre stage," Nature, Nature, vol. 526(7573), pages 351-360, October.
    3. Bo Wang & Jing Chen & Julia S. Caserto & Xi Wang & Minglin Ma, 2022. "An in situ hydrogel-mediated chemo-immunometabolic cancer therapy," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Justin M. Wolter & Hanqian Mao & Giulia Fragola & Jeremy M. Simon & James L. Krantz & Hannah O. Bazick & Baris Oztemiz & Jason L. Stein & Mark J. Zylka, 2020. "Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA," Nature, Nature, vol. 587(7833), pages 281-284, November.
    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. Heathcliff Dorado García & Fabian Pusch & Yi Bei & Jennifer Stebut & Glorymar Ibáñez & Kristina Guillan & Koshi Imami & Dennis Gürgen & Jana Rolff & Konstantin Helmsauer & Stephanie Meyer-Liesener & N, 2022. "Therapeutic targeting of ATR in alveolar rhabdomyosarcoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Chih-Hao Wang & Tadataka Tsuji & Li-Hong Wu & Cheng-Ying Yang & Tian Lian Huang & Mari Sato & Farnaz Shamsi & Yu-Hua Tseng, 2024. "Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Tiantian Jing & Dianhui Wei & Xiaoli Xu & Chengsi Wu & Lili Yuan & Yiwen Huang & Yizhen Liu & Yanyi Jiang & Boshi Wang, 2024. "Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    4. 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.
    5. Jian Wang & Yuxi Teng & Ruihua Zhang & Yifei Wu & Lei Lou & Yusong Zou & Michelle Li & Zhong-Ru Xie & Yajun Yan, 2021. "Engineering a PAM-flexible SpdCas9 variant as a universal gene repressor," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    6. Boris Kantor & Bernadette O’Donovan & Joseph Rittiner & Dellila Hodgson & Nicholas Lindner & Sophia Guerrero & Wendy Dong & Austin Zhang & Ornit Chiba-Falek, 2024. "The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. Jasmin Bartl & Marco Zanini & Flavia Bernardi & Antoine Forget & Lena Blümel & Julie Talbot & Daniel Picard & Nan Qin & Gabriele Cancila & Qingsong Gao & Soumav Nath & Idriss Mahoungou Koumba & Mariet, 2022. "The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Xiaoming Hu & Shuang Wang & Shaotong Fu & Meng Qin & Chengliang Lyu & Zhaowen Ding & Yan Wang & Yishu Wang & Dongshu Wang & Li Zhu & Tao Jiang & Jing Sun & Hui Ding & Jie Wu & Lingqian Chang & Yimin C, 2023. "Intranasal mask for protecting the respiratory tract against viral aerosols," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. Arpiar Saunders & Kee Wui Huang & Cassandra Vondrak & Christina Hughes & Karina Smolyar & Harsha Sen & Adrienne C. Philson & James Nemesh & Alec Wysoker & Seva Kashin & Bernardo L. Sabatini & Steven A, 2022. "Ascertaining cells’ synaptic connections and RNA expression simultaneously with barcoded rabies virus libraries," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    10. William C. W. Chen & Leonid Gaidukov & Yong Lai & Ming-Ru Wu & Jicong Cao & Michael J. Gutbrod & Gigi C. G. Choi & Rachel P. Utomo & Ying-Chou Chen & Liliana Wroblewska & Manolis Kellis & Lin Zhang & , 2022. "A synthetic transcription platform for programmable gene expression in mammalian cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    11. Julia Joung & Paul C. Kirchgatterer & Ankita Singh & Jang H. Cho & Suchita P. Nety & Rebecca C. Larson & Rhiannon K. Macrae & Rebecca Deasy & Yuen-Yi Tseng & Marcela V. Maus & Feng Zhang, 2022. "CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    12. Xin Wu & Yuanhuan Yu & Meiyan Wang & Di Dai & Jianli Yin & Wenjing Liu & Deqiang Kong & Shasha Tang & Meiyao Meng & Tian Gao & Yuanjin Zhang & Yang Zhou & Ningzi Guan & Shangang Zhao & Haifeng Ye, 2024. "AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    13. Liam McAllan & Damir Baranasic & Sergio Villicaña & Scarlett Brown & Weihua Zhang & Benjamin Lehne & Marco Adamo & Andrew Jenkinson & Mohamed Elkalaawy & Borzoueh Mohammadi & Majid Hashemi & Nadia Fer, 2023. "Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    14. Tian Zhou & Xinyi Zhu & Zhizhong Ye & Yong-Fei Wang & Chao Yao & Ning Xu & Mi Zhou & Jianyang Ma & Yuting Qin & Yiwei Shen & Yuanjia Tang & Zhihua Yin & Hong Xu & Yutong Zhang & Xiaoli Zang & Huihua D, 2022. "Lupus enhancer risk variant causes dysregulation of IRF8 through cooperative lncRNA and DNA methylation machinery," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    15. Shaela Wright & Xujie Zhao & Wojciech Rosikiewicz & Shelby Mryncza & Judith Hyle & Wenjie Qi & Zhenling Liu & Siqi Yi & Yong Cheng & Beisi Xu & Chunliang Li, 2023. "Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    16. Haipeng Fu & Tingyu Wang & Xiaohui Kong & Kun Yan & Yang Yang & Jingyi Cao & Yafei Yuan & Nan Wang & Kehkooi Kee & Zhi John Lu & Qiaoran Xi, 2022. "A Nodal enhanced micropeptide NEMEP regulates glucose uptake during mesendoderm differentiation of embryonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    17. Yafeng Wang & Guiquan Zhang & Qingzhou Meng & Shisheng Huang & Panpan Guo & Qibin Leng & Lingyun Sun & Geng Liu & Xingxu Huang & Jianghuai Liu, 2022. "Precise tumor immune rewiring via synthetic CRISPRa circuits gated by concurrent gain/loss of transcription factors," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    18. Haobo Han & Jiakai Xing & Wenqi Chen & Jiaxin Jia & Quanshun Li, 2023. "Fluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    19. Deqiang Kong & Yang Zhou & Yu Wei & Xinyi Wang & Qin Huang & Xianyun Gao & Hang Wan & Mengyao Liu & Liping Kang & Guiling Yu & Jianli Yin & Ningzi Guan & Haifeng Ye, 2024. "Exploring plant-derived phytochrome chaperone proteins for light-switchable transcriptional regulation in mammals," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    20. Hanna Vihma & Kelin Li & Anna Welton-Arndt & Audrey L. Smith & Kiran R. Bettadapur & Rachel B. Gilmore & Eric Gao & Justin L. Cotney & Hsueh-Cheng Huang & Jon L. Collins & Stormy J. Chamberlain & Hyeo, 2024. "Ube3a unsilencer for the potential treatment of Angelman syndrome," Nature Communications, Nature, vol. 15(1), pages 1-16, 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_s41467-022-35580-z. 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.