Development of the Gastrobody platform to combat Clostridium perfringens toxins

抗体是一种蛋白质，可以结合特定的目标，如细菌、病毒或毒素，阻止它们引起疾病。抗体在农业中没有广泛应用，因为和饮食中的几乎所有蛋白质一样，它们很快就会被胃和小肠破坏。我们通过改造大豆中的一种蛋白质来结合新的靶标，从而产生了“胃小体”。与抗体或其他蛋白质支架不同，胃小体对肠道中苛刻的消化酶具有很强的抵抗力。在这里，我们将测试胃小体抵御细菌性疾病的能力。产气荚膜梭状芽胞杆菌是一种细菌，可导致影响农民的多种疾病，包括猪、牛、羊和鸡。这些影响是由细菌释放的毒素引起的。我们将建立能够阻止肠道中这些细菌毒素造成损害的胃体。我们将重点关注导致鸡坏死性肠炎的毒素，在禁止在动物饲料中使用抗生素后，这种毒素急剧增加，每年在世界范围内造成数十亿英镑的损失。我们的目标是建立具有成本效益的胃小体生产，这样它们就可以简单地添加到动物饲料中，然后在消化系统中识别特定的目标。这些目标应该为广泛使用胃体来促进肠道健康奠定基础，这与许多农业和医学疾病有关。

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.