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<p>The ability of bacteria and viruses to selectively replicate in tumours has led to synthetic engineering of new microbial therapies. Here we design a cooperative strategy whereby <i>Salmonella typhimurium</i> bacteria transcribe and deliver the Senecavirus A RNA genome inside host cells, launching a potent oncolytic viral infection. ‘Encapsidated’ by bacteria, the viral genome can further bypass circulating antiviral antibodies to reach the tumour and initiate replication and spread within immune mice. Finally, we engineer the virus to require a bacterially delivered protease to achieve virion maturation, demonstrating bacterial control over the virus. Together, we refer to this platform as ‘CAPPSID’ for Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery. This work extends bacterially delivered therapeutics to viral genomes, and shows how a consortium of microbes can achieve a cooperative aim.</p>

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Engineered bacteria launch and control an oncolytic virus

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月15日

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  • Zakary S. Singer,
  • Jonathan Pabón,
  • Hsinyen Huang,
  • William Sun,
  • Hongsheng Luo,
  • Kailyn Rhyah Grant,
  • Ijeoma Obi,
  • Courtney Coker,
  • Charles M. Rice,
  • Tal Danino

摘要

The ability of bacteria and viruses to selectively replicate in tumours has led to synthetic engineering of new microbial therapies. Here we design a cooperative strategy whereby Salmonella typhimurium bacteria transcribe and deliver the Senecavirus A RNA genome inside host cells, launching a potent oncolytic viral infection. ‘Encapsidated’ by bacteria, the viral genome can further bypass circulating antiviral antibodies to reach the tumour and initiate replication and spread within immune mice. Finally, we engineer the virus to require a bacterially delivered protease to achieve virion maturation, demonstrating bacterial control over the virus. Together, we refer to this platform as ‘CAPPSID’ for Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery. This work extends bacterially delivered therapeutics to viral genomes, and shows how a consortium of microbes can achieve a cooperative aim.