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Abstract

Our project focuses on developing a novel treatment for hematological disorders caused by an iron overload, such as hemochromatosis and thalassemia. These autosomal recessive disorders have symptoms including cirrhosis, arthritis, and heart failure, which result from overabsorption of iron from the duodenum. Although these are among the most common heritable disorders, treatments for iron overload are limited. Even today it is mostly treated by frequent bloodletting, which not all patients can support. The aim of our project is to combat these disorders at the source by developing a therapy that prevents the intestinal absorption of iron.

Using the Ferric Uptake Regulation (FUR) system that controls siderophore biosynthesis (iron chelator), we engineer Escherichia coli in order to produce these siderophores in response of high concentrations of iron. To reduce the patient's iron absorption, our bacteria are encapsulated in a polymer that can be ingested during a meal. The capsule degrades specifically in the duodenum to release the engineered bacteria, which respond to ambient iron by producing siderophores at their full potential. Once the iron is chelated, it is no longer absorbable by the patient.