Transgenic hookworm secreting human s16-HuScFv antibody partially neutralizes tetrodotoxin in host circulation.

Biologic therapies are effective but face significant hurdles due to the need for frequent parenteral administration, which drives up costs and reduces patient compliance. This creates an urgent demand for novel, sustained-release delivery platforms capable of continuous, safe, and efficient in situ biologic production within the host. Hookworms, known for their ability to secrete various proteins and establish long-term infections, present a unique, disease-agnostic bioengineered platform for this purpose, potentially offering years of therapeutic delivery from a single dose for chronic human diseases.

Researchers engineered the Ancylostoma ceylanicum secretome by inserting a human single-chain variable fragment antibody, s16-HuScFv, into its genome. They confirmed successful transgene expression, noting it did not perturb surrounding gene expression, and established heritable transgenesis. The primary endpoint was to assess if the s16-HuScFv transgene product was secreted into host circulation and its ability to neutralize tetrodotoxin, serving as a proof-of-concept for this novel delivery platform. The study utilized a bioengineered hookworm platform to manufacture and deliver biologic therapeutics in vivo.

The study successfully demonstrated that the engineered Ancylostoma ceylanicum hookworm could express and secrete a therapeutic biologic. Transgene insertion of the s16-HuScFv did not disrupt the surrounding gene expression profile of the hookworm, indicating a stable genetic modification. Furthermore, heritable transgenesis was confirmed, ensuring the genetic modification could be passed down through generations of the parasite. This stability is crucial for a long-term delivery platform.

The s16-HuScFv transgene product was confirmed to be secreted into the host's circulation, validating the hookworm's potential as an in vivo delivery vehicle. Crucially, the secreted s16-HuScFv was shown to partially neutralize tetrodotoxin, providing a direct proof-of-concept for the functional delivery of a therapeutic antibody. While the abstract does not provide specific quantitative metrics like percentages or p-values for neutralization efficacy, the qualitative finding of partial neutralization is significant.