Enteropathogenic E. coli T3SS can be adopted for efficient secretion of human IFN

Type I Interferons are a group of cytokines with immunomodulatory, antiproliferative and antiviral properties. They have become widely used therapeutics for the treatment of cancer and viral diseases. Like many other protein-based drugs, IFNs are degraded in GI tract. This precludes oral delivery; so IFN is usually administered parenterally. Developing an oral delivery tool for IFN and other protein-based therapeutics would reduce cost, complexity and increase safety.

Here we explore if an enteropathogenic bacteria, EPEC, can be used as an oral delivery vector. EPEC survives the harsh conditions of the stomach to reach the small intestine. Once there, it activates a multiprotein syringe complex, the type III secretion system (T3SS). This virulence system is used by the bacteria to translocate effector proteins across the bacterial envelope into eukaryotic host cells.

We generated a non-virulent strain of EPEC that expresses human IFNα2 that is targeted for secretion via the T3SS. This strain lacks the ability to attach to the host cells, but has a functional secretion system that transports proteins into the growth media.

We have shown that our modified EPEC can efficiently produce and secrete human IFNα2. This secreted IFN exhibits antiproliferative and antiviral activities in vitro similar to those of commercial IFNs.

We have taken the first steps towards showing that engineered bacteria can be used for the oral delivery of IFN. The approach is general and so holds promise for delivering other protein-based drugs.