Team:Amazonas-Brazil/Integrated
Synthetic Biology and Development of Probiotics
Thinking of how our therapy could be applied in real life, we talked to experts from Synlogic Therapeutics, a company that uses synthetic biology to design living therapeutics. Our doubts were related to design, administration and protein of interest for therapy and choosing the protein of interest for therapy.
According to Lubkowicz and Cotton, the delivery method should vary for every tumor. If it is placed in the gut, orally is better; in another site, maybe intravenously would be the best alternative.
They got interested in our strategy. For them, it was the best way to keep the system off when you don't want it to be on. They also gave the idea of combining proteins for therapy and advised us to use a mid-copy plasmid.
Biosafety and Design
BeliEVE’s first approach was based on the gene Invasin, isolated from Yersinia pseudotuberculosis. It would allow BeliEVE to break into eukaryotic cells and deliver targeted drugs inside cancer cells. We consulted Dr. Anderson about our synthetic genetic circuit design, and he advised us to manipulate our engineered bacteria in a laboratory safety risk level 2, following the NIH Guidelines that pathogenicity-related genes in another organism result in a group risk 2 organism. Since our Synthetic Biology Laboratory is currently level 1, we changed our design to deliver the medicines using the secretion system alpha-hemolysin.
Choose of Chassis
The choice of a chassis is a fundamental step in the design of living therapeutics. Our first choice for chassis was Salmonella sp., which naturally invades solid tumors. However, guidelines for microorganisms manipulation recommend that this bacteria must be handled only in a laboratory risk level 2. In a consult with professor Pedrolli, she advised us to choose and use a probiotic strain. The advantages of a probiotic include: easy manipulation and cultivation and would be better indicated for systemic treatment. Prof. Pedrolli also believes that if regulatory agencies release the use of bacterias for cancer treatment, probiotics would be the first ones to be released.
Oncology Perspective
To better understand how BeliEVE can target cancer we talked with Dr. Tiburcio. He studies Melanoma Microenvironment and enlighted our vision about the components of tumors, pro-tumorigenic and anti-tumorigenic pathways and current approaches for therapy such as immunotherapy, and how it can be influenced by the human host microbiome. He comprehends that “Cancer is a generalist name for a group of complex diseases. Every cancer is different”. After our conversation, we concluded that the best choice was to design a circuit that is sensitive to the general characteristic of solid tumors to serve as a model for future real therapy.
Immunology Perspective
He comprehends that it would be interesting to fine-tuning the biosensor by giving the bacteria the notion of how much medicine is necessary to execute the therapy, what depends on the relation of the selected protein to execute the therapy and its biological effects, and the capacity of production for each single bacteria. We agree with him and these suggestions are part of our future prospects..
Psychology Perspective
When we were looking for professionals that had experience with patients, we found Dr. Maria Graciete Ribeiro Carneiro who is chief Psychologist of the Amazonas Oncology Control Center Foundation (FCECON) and has more than 25 years of experience on working with cancer patients. Talking to her, we learned that the psychological accompaniment of oncologic patients is essential because of the physical and mental destructive character of the disease. “Their (patients) lives pass through a lot of negative changes (…) it’s easy to feel abandoned, left behind (…)”. Our conversation with her directed our attention to the importance of the development of therapies that can make patients’ lives better, allied with social approaches that ensure support and care to the patients.
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