Team:UFMG Brazil/Overview

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Overview

This year, UFMG_Brazil iGEM team project aims to create a new system of drug production and delivery based on an attenuated strain of Leishmania phagocytized by macrophages.

Mediators of inflammation induced by macrophages are critical for a variety of human inflammatory disorders, such as sepsis microbial infection, acute brain/lung/hepatic/renal injuries, neurodegenerative disorders, osteoporosis/osteonecrosis, cardiovascular and metabolic diseases, and autoimmune diseases.

Once activated, macrophages actively secrete and cause an imbalance of cytokines, chemokines, and mediators of inflammation.

The protozoan Leishmania is a good new chassi, first of all because of it’s ability to infect macrophages efficiently.

Therefore, its application should reduce toxicity due to systemic effects. Also, because it has the ability to express proteins with proper post-translational modifications, and deliver these proteins inside macrophages.

We aim to deliver Interferon beta (IFN-β), that is already used as a treatment for some inflammatory joint diseases, to induce clinical improvement due to decreased synovial inflammation and protection against joint destruction.

Our project acts on the treatment of inflammatory joint diseases by producing IFN-β, a drug that is used to treat Rheumatoid Arthritis (RA), with a modelling system based on the Gout.

Safety: The visceral Leishmania donovani strain with the virulence factor Centrin-1 deleted has very low risks of contamination, and its virulence reduction has been evaluated and confirmed with different animal models, such as mice, hamsters, and dogs.