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<p>Biologics, protein- and peptide-based drugs derived from living organisms or cell lines have emerged as effective therapies across a broad range of indications. However, parenteral administration and the need for frequent dosing increase costs and limit compliance, creating an urgent need for innovative platforms capable of continuously, safely, and efficiently delivering sustained biologics in situ within the host. Here, we describe a bioengineered hookworm platform to manufacture and deliver biologic therapeutics in vivo. As proof of concept, we engineer the <i>Ancylostoma ceylanicum</i> secretome by inserting a human single-chain variable fragment antibody (s16-HuScFv) into its genome. Transgene expression does not perturb surrounding gene expression, and heritable transgenesis is confirmed. The s16-HuScFv transgene product is secreted into host circulation and partially neutralizes tetrodotoxin. Given the availability of controlled human infections, our disease-agnostic bioengineered hookworm platform offers a next-generation approach to address a suite of chronic human diseases, and with a single-dose administration, could potentially produce and deliver biologic medicines within the human host for years.</p>

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Transgenic hookworm secretes anti-tetrodotoxin human single chain antibody

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月3日

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  • Kumar Sachin Singh,
  • Suman Bharti,
  • Bruce A. Rosa,
  • Mahdiyeh Bigham,
  • Samuel C. Uzoechi,
  • Young-Jun Choi,
  • John C. Martin,
  • Danielle Kemper,
  • Slavica Pavlovic Djuranovic,
  • Darren A. Pickering,
  • Rachael Ryan,
  • Bethany K. Bracken,
  • Maria Elena Bottazzi,
  • Eric C. Carnes,
  • Wannaporn Ittiprasert,
  • Matthew Moyle,
  • Paul J. Brindley,
  • Alex Loukas,
  • Sergej Djuranovic,
  • Makedonka Mitreva

摘要

Biologics, protein- and peptide-based drugs derived from living organisms or cell lines have emerged as effective therapies across a broad range of indications. However, parenteral administration and the need for frequent dosing increase costs and limit compliance, creating an urgent need for innovative platforms capable of continuously, safely, and efficiently delivering sustained biologics in situ within the host. Here, we describe a bioengineered hookworm platform to manufacture and deliver biologic therapeutics in vivo. As proof of concept, we engineer the Ancylostoma ceylanicum secretome by inserting a human single-chain variable fragment antibody (s16-HuScFv) into its genome. Transgene expression does not perturb surrounding gene expression, and heritable transgenesis is confirmed. The s16-HuScFv transgene product is secreted into host circulation and partially neutralizes tetrodotoxin. Given the availability of controlled human infections, our disease-agnostic bioengineered hookworm platform offers a next-generation approach to address a suite of chronic human diseases, and with a single-dose administration, could potentially produce and deliver biologic medicines within the human host for years.