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Design of bacteriophage T4-based artificial viral vectors for human genome remodeling

Author

Listed:
  • Jingen Zhu

    (The Catholic University of America)

  • Himanshu Batra

    (The Catholic University of America)

  • Neeti Ananthaswamy

    (The Catholic University of America)

  • Marthandan Mahalingam

    (The Catholic University of America)

  • Pan Tao

    (The Catholic University of America)

  • Xiaorong Wu

    (The Catholic University of America)

  • Wenzheng Guo

    (The Catholic University of America)

  • Andrei Fokine

    (Purdue University)

  • Venigalla B. Rao

    (The Catholic University of America)

Abstract

Designing artificial viral vectors (AVVs) programmed with biomolecules that can enter human cells and carry out molecular repairs will have broad applications. Here, we describe an assembly-line approach to build AVVs by engineering the well-characterized structural components of bacteriophage T4. Starting with a 120 × 86 nm capsid shell that can accommodate 171-Kbp DNA and thousands of protein copies, various combinations of biomolecules, including DNAs, proteins, RNAs, and ribonucleoproteins, are externally and internally incorporated. The nanoparticles are then coated with cationic lipid to enable efficient entry into human cells. As proof of concept, we assemble a series of AVVs designed to deliver full-length dystrophin gene or perform various molecular operations to remodel human genome, including genome editing, gene recombination, gene replacement, gene expression, and gene silencing. These large capacity, customizable, multiplex, and all-in-one phage-based AVVs represent an additional category of nanomaterial that could potentially transform gene therapies and personalized medicine.

Suggested Citation

  • Jingen Zhu & Himanshu Batra & Neeti Ananthaswamy & Marthandan Mahalingam & Pan Tao & Xiaorong Wu & Wenzheng Guo & Andrei Fokine & Venigalla B. Rao, 2023. "Design of bacteriophage T4-based artificial viral vectors for human genome remodeling," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38364-1
    DOI: 10.1038/s41467-023-38364-1
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    References listed on IDEAS

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    1. Lei Sun & Xinzheng Zhang & Song Gao & Prashant A. Rao & Victor Padilla-Sanchez & Zhenguo Chen & Siyang Sun & Ye Xiang & Sriram Subramaniam & Venigalla B. Rao & Michael G. Rossmann, 2015. "Cryo-EM structure of the bacteriophage T4 portal protein assembly at near-atomic resolution," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    2. Martin P. Stewart & Armon Sharei & Xiaoyun Ding & Gaurav Sahay & Robert Langer & Klavs F. Jensen, 2016. "In vitro and ex vivo strategies for intracellular delivery," Nature, Nature, vol. 538(7624), pages 183-192, October.
    3. Siyuan Yu & Han Yang & Tingdong Li & Haifeng Pan & Shuling Ren & Guoxing Luo & Jinlu Jiang & Linqi Yu & Binbing Chen & Yali Zhang & Shaojuan Wang & Rui Tian & Tianying Zhang & Shiyin Zhang & Yixin Che, 2021. "Efficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Qianglin Fang & Wei-Chun Tang & Pan Tao & Marthandan Mahalingam & Andrei Fokine & Michael G. Rossmann & Venigalla B. Rao, 2020. "Structural morphing in a symmetry-mismatched viral vertex," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
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