Engineered probiotics are a growing technology that has the power to revolutionize the way we treat and prevent diseases. With that in mind, we focused our Human Practices activities on spreading the word about engineered probiotics. We created a collection of parts in the Registry of Standard Biological Parts and participated in Brazilian's regulatory agency public consultation about probiotics. Come with us and learn more about our HP activities!
When we started working with genetically engineered probiotics, we went to the Registry of Standard Biological Parts to look for parts that could be useful in our project, especially regarding the chassis Bacillus subtilis and Lactococcus lactis. That was a frustrating experience: it was super hard to find these parts even knowing that several past teams had already worked with engineered probiotics. So, we thought: why not create a collection with all the parts we can find and might be useful to engineer probiotics?
We started to look for every team since iGEM has begun, that had worked with engineered probiotics or created related parts that could be useful to engineer them. After creating a list of teams, projects, and parts, we categorized them first by the most common probiotic chassis: Escherichia coli, Lactococcus lactis, Lactobacillus spp. and Bacillus subtilis. Then, we separated these parts by function, into four categories.
- Sense and control: this category contains promoters and regulatory proteins that are useful to create regulatory circuits that respond to environmental signals;
- Production and delivery: this category contains coding sequences for proteins that have a therapeutical function or other desired function for the engineered probiotic, also contains coding sequences for signal peptides for the secretion and delivery of a protein of interest;
- Biocontainment: this category contains coding sequences or devices that can be used to create an inducible kill-switch;
- Memory: this category contains coding sequences or devices that can be used to record an environmental signal.
To access the collection, click here.
We invite other teams to collaborate and submit new parts in this collection by categorizing them in the submission parts form. To do that, when choosing the category select:
Besides creating the Collection at the Registry, we also published the review "Engineering Microbial Living Therapeutics: The Synthetic Biology Toolbox" in Trends in Biotechnology by CellPress as a part of ReviewSeries: iGEM Perspectives on Synthetic Biology. In this review, we present the available parts to engineer living therapeutics and the parts available at the Registry. You can find it here.
We hope this collection to be useful for future teams interested in working with genetically engineered probiotics and help them find parts easily.
ANVISA's Public Consultation
The gaps in Brazilian legislation
Brazilian legislation is still in its first steps when it comes to genetically engineered organisms. ANVISA (Brazilian National Health Surveillance Agency) is the agency in charge of regulating all the health-related products such as drugs, food, and cosmetics in Brazil and who oversees regulating GMOs is CTNBio (National Technical Commission for Biosafety). However, when a health-related product holds a genetically modified organism both agencies need to work together to approve the product, however it is not easy for ANVISA to properly label and address this new product due the presence of a GMO, and a product that is hard to address entail to a slow in the regulation process. Therefore, genetically engineered products need a proper labeling in the ANVISA’s legislation. Besides that, not much about GMOs was covered in the current legislation. Genetic engineering is currently researched and studied all across the globe, and laws need to follow this new trend.
What the Agency did to overcome this limitation?
Even though the agency covers a lot of fields, the field of food supplements in general, including probiotics, required updates. Because of that ANVISA launched a public consultation about this topic.
How we tackled this issue?
Our team knew that participating in such a consultation would be key to change how the Brazilian government deals with probiotics (which is the main topic of our research project). ANVISA created this public consultation in regards to opening a proposal that establishes and regulate food supplements such as bioactive substances, enzymes, and probiotics. Our main goal was to include in the legislation genetically engineered food supplement and to prove that this topic is interesting and important to Brazilian researchers, also raising awareness about it. Many big international companies and entities participated in the consultation, including Bayer SA, Pfizer, Nestlé, Yakult, International Probiotics Association, The International Scientific Association for Probiotics and Prebiotics, and of course iGEM UNESP team.
Our contribution to the public consultation
We were able to send different suggestions regarding changing what has been written in the original legislation. We suggested changes in the definition of probiotics, the tests needed to certify the safety of the food supplement and other related topics. Since the main goal of our team is to develop a genetically engineered probiotic all these suggestions were very needed. Articles, researches, and books references were used to sustain the suggestions. However, most of our indications were similar to what other people have written and suggested. Nevertheless, our main contribution was regarding the use and control of genetically engineered organism in food supplements, even though we had a legislation and laws regarding probiotic, nothing was said about genetically engineered products. Using research papers and even our own research material we managed to sustain our suggestion, leaving it clear that genetically engineered probiotic is a studied and invested topic, therefore, a legislation regarding it needs to be created.
What kind of an impact it is making?
After that, a reunion occurred at ANVISA head office in Brasilia, where all the suggestions were discussed being accepted or rejected. A month later the results came. Most of our suggestions were accepted. Our contribution about including genetically engineered organisms in food supplements was accepted but with a reservation, the genetically engineered product would need first to be approved by the CTNBio and then it would be analyzed by ANVISA.
Why is it important?
That's a huge step because even though CTNBio deals with GMO it can't regulate probiotics. Before our contribution, a genetically engineered probiotic would first be analyzed by CTNBio but after that ANVISA would not allow it to be produced because there wasn't any topic regarding it existing, thus, it would be needed to create a special validation process for this product, making the whole process take even longer. After our contribution, ANVISA would simply require the needed tests and after that, the product would be accepted to be produced. This represents a key change since a regular ANVISA validation process takes around five years.
Our contribution also represents the need for a more updated legislation that fulfills the needs of the new researches across our country. Genetic Engineering is being studied in almost every state and region in Brazil, the laws that regulate science need to follow this trend.
You can find the public consultation here and the report where our proposals were accepted here (in Portuguese).
Integrated Human Practices
Dialog with Libbs Pharmaceutical
Early this year we got in touch with Libbs, a Brazilian pharmaceutical company and one of the top 10 biggest players in the Brazilian pharmaceutical market. We had video conferences with Dr. Rafaela Gouveia and Dr. Giuliano Barissa, both from the External Research & Development department at Libbs. We talked about their thoughts on our project and our technology, and gave us unique insights about how we could build something that could be really interesting and useful to pharmaceutical companies: questions about safety, cost, scale-up, market, and regulations.
At the first time we met, we talked about our 2017’s iGEM project, Insubiota, that aims to offer an alternative treatment for type 1 diabetes with an engineered probiotic, and they suggested that we could apply this technology to other diseases and metabolic disorders, like lactose intolerance. We started to think how we could improve our previous project in a way that would be easy to change the parts in the circuits. That motivated us to design and build a framework useful to easily engineer probiotics to treat other diseases rather than just type 1 diabetes, and that was the birth of our framework: Hope.
Additionally, they informed us about and invited us to participate in an ANVISA - National Health Surveillance Agency (Brazilian regulatory agency) public consultation that was open by that time about probiotics, that they and several other pharmaceutical companies were participating, and would be awesome to have people outside the pharmaceutical companies participating as well. Because we believe laws and regulation must be built with the community, we answered the call and participate in the public consultation.
In our document, we explained about engineered probiotics, their importance and applications, and why they should be included in regulation and we were super happy and excited when we found out that our suggestions were accepted by ANVISA and engineered probiotics were included in the regulation! You can learn all about our work with ANVISA by clicking here.
In addition to our conversations, later in the year, we arranged a visit to Libbs so we could talk with Dr. Rafaela in person, tell her about our project and our progress, and visit the production plant of pharmaceuticals and biopharmaceuticals.
We still keep in contact with Libbs and we love to hear their thoughts and insights about our project and we hope we could build great things together to solve real-world problems!
Intellectual Property with Lawyer David Soares da Silva
Over this year we got in touch with David Soares da Silva and Clarissa Jucá Gallo, two big supporters of our team. David is a lawyer who has collaborated with our team since last year. This year he came to our College in Araraquara to know us personally, learn more about our project and to instruct us on ways to legally protect our work, talking to us about important information on intellectual property and legislation that can help us to carry out our work. His suggestions and insights may also help us in founding a startup in the future. We are grateful for meeting David and Clarissa, all the support we have received from them, and we hope to accomplish great things together in the future.