Development of the Gastrobody platform to combat Clostridium perfringens toxins

Antibodies are proteins that can bind specific targets such as bacteria, viruses or toxins to stop them causing disease. Antibodies are not widely used in agriculture because, like nearly all proteins in the diet, they are quickly destroyed by the stomach and small intestine. We have generated "gastrobodies" by engineering a protein from soybeans to bind new targets. Unlike antibodies or other protein scaffolds, gastrobodies are highly resistant to the harsh digestive enzymes of the gut. Here we will test the ability of gastrobodies to protect against bacterial disease. Clostridium perfringens is a bacterium that causes a wide range of diseases affecting farmers, including in pigs, cows, sheep and chickens. These effects are caused by toxins released by the bacterium. We will establish gastrobodies that can stop these bacterial toxins in the gut from causing damage. We will focus on the toxins that cause necrotic enteritis in chickens, which has increased dramatically following the banning of antibiotics in animal feed and costs billions of pounds per year worldwide. We aim to establish the cost-effective production of gastrobodies, so that they can be simply added to animal feed and then recognise specific targets within the digestive system. These goals should set the stage for broad use of gastrobodies for gut health, with relevance to many agricultural and medical diseases.