Transgenic hookworm secretes anti-tetrodotoxin human single chain antibody

Biologics, protein- and peptide-based drugs derived from living organisms or cell lines have emerged as effective therapies for broad indications. However, parenteral administration and frequent dosing needs increase costs and limit compliance, so there is an urgent need for innovative platforms capable of continuously, safely, and efficiently delivering sustainable biologics in situ within patients. Here we present a bioengineered hookworm platform to produce and deliver biologic medicines within patients. Hookworms can be safely administered and live for years, reducing repeated administrations and improving adherence for chronic disease treatment. We provide proof-of-concept through bioengineered secretomes, by inserting a human single chain variable fragment antibody (s16-HuScFv) that neutralizes tetrodotoxin. We inserted s16-HuScFv into the hookworm Ancylostoma ceylanicum genome and confirmed germline transmission via transcriptome sequencing of F1 eggs.