GENOVA Project

For the past months we have seen that our health, security and life has been threaten by a virus and we have shown that we were and are not fully prepared for this situations. For this reason GENOVA Project is fully compromised on designing and developing a new delivery system for efficient and safe DNA vaccination. 

As a solution, we proposed a modified bacteria that is able to carry and deliver DNA vaccines to dendritic cells in the gut, when it is orally administrated. The main reason of this delivery system that we are proposing is that using living bacteria induces a strong cell and humoral immune response in the patient. 

Finally, this idea will change lives globally, since it this alternative allow a quick vaccine production, even in large scale and its way of administration makes it available for everyone, even if they can not access correct health services.

For a long time, vaccination has been a challenge that has taken scientists to develop new methods and systems to improve and accelerate human immunization against different viral infections that threaten human life. New technologies as DNA and mRNA vaccination became a reality in past years, to enable transference of genetic information that protect people effectively from potential illnesses.

Due to the current outbreak generated by SARS-CoV-2 the efforts of the scientific community have focused on research and development of vaccines and treatments against the virus. Based on numbers from Johns Hopkins Coronavirus research center, until May 30th, 2020, this sanitary emergency has reached more than 6 million cases and 367,356 deaths worldwide, therefore the relevance of this project.

In addition, we have taken the current situation to focus our project not only to investigate an alternative for a vaccine, but to develop and study a full innovative delivery system for DNA vaccines, so they can be easily produced and applied, and effective generating immune responses.

Due to the current outbreak generated by SARS-CoV-2 the efforts of the scientific community have focused on research and development of vaccines and treatments against the virus. Therefore we have focused our project towards finding an alternative delivery system and vaccine against the current coronavirus pandemic.

The objective of this project is to characterize the delivery system and design a DNA vaccine that targets dendritic cells in human systems to generate an  immune response against novel coronavirus. The relevant feature of this vaccine is the use of living bacteria as DNA carriers to transfer a plasmid containing cDNA  of the S viral gene to dendritic cells, making it specific by using PRRs present on this cells and controlling bacterial growth with different synthetic biology tools.

Therefore we propose an orally administered vaccine that may induce strong mucosal humoral and cellular immunity and may produce long-live immunization. In addition, this kind of administrations do not require skills as intramuscular vaccine making it easier and affordable for its use in different communities and regions.

This solution may offer an alternative way of preventing SARS-CoV-2 in the complete world population, therefore the relevance of the project, as the main purpose is to make it available for every person so the current situation may be stopped.

Also, this solution may open a new area of study in Biotechnology and Medicine, as it gives the possibility of studying a new way of preventing not only viral but other diseases that may require protein delivery of interest molecules. In addition, it may help to continue studying and developing DNA vaccines as a real  solutions. 

For this reasons we consider that our project may not only impact health in the current situation, but the scientific world, in order to continue developing different solutions for health threats.

Since the aims of this Challenge are to develop and support ideas that may solve global threats, in this case related to health and pandemics, we consider that out project fits perfectly with the objectives of this initiative. 

Firstly because the global perspective that we are presenting, related to the target population that makes not only relevant for us or a parte of the scientific community, but to everyone in any country. Finally, the problem and solution gives an alternative that is focused in the main topic of this Challenge. Therefore we think it may have a change to materialize.

Normally, vaccination is carried out by using viral proteins or viral particles to induce the immune response of the patient, but in the las years new technologies have been developed to generate new vaccines using genetic material, either DNA o mRNA. For the current pandemic, the approaches have been focused on the traditional vaccine types or in mRNA, but there has not been a significant advance on DNA vaccinations, also it has not been taken into account by many researchers during this outbreak.

Consequently, we decided to focus our project not only in an alternative that has been studied in past years, but we have innovated, since we propose to design attenuated bacteria that can carry DNA and that can target specifically dendritic cells in the gut, so the DNA can be correctly transferred and expressed there. An other important feature that we proposed, is that by using genetic engineering we can design a bacteria that can be controlled to stop cellular division when it is place in its final solution for oral administration, so it will not represent any threat when administrated.

Finally, this solution will enable a rapid and massive production, since bacteria can be cultivated in bioreactors that aloud them to grow exponentially, taking into account that the bacterial strains taken into account in our previous study divide in less than an hour. This feature is important, since it will help to make it available for anyone anywhere.

The most important technology that we are using is genetic engineering, which is not fully new, but is has shown relevant advances in the las years. This technology involves the use of plasmid DNA, DNA sequencing, restriction enzymes and ligases protocols for design of the DNA vaccine. 

Also, it requires technologies for bacterial transformation and testing, since we need to be sure that our DNA vaccine is correctly designed and introduced in the bacteria. The technologies required for this are, PCR, gel electrophoresis, SDS-PAGE analysis and western blot, in addition to further protocols required by the FDA and other organisms to carry out the preclinical and clinical trails.

Also, we require bioinformatic tools as Benchling and tools from New England Biolabs or ThermoFisher Scientific, since they area available to design and check the prototypes that we will use in the laboratory research.

Since we have done a complete theoretical research, but not a laboratory or practical research, we only have our work and our references to support our project. It is important to mention that other bacterial-related vaccines have been done and tried in past years and recent studies have shown it as a promising alternative, that works correctly not only in theory but in practice. As part of this we want to share the most important papers that has been done in this field and that is published in the most relevant science websites.

1. Live Bacterial Vectors—A Promising DNA Vaccine Delivery System
2. Oral Immunization with a Recombinant Lactococcus lactis–Expressing HIV-1 Antigen on Group A Streptococcus Pilus Induces Strong Mucosal Immunity in the Gut
3. A novel plasmid for delivering genes into mammalian cells with noninvasive food and commensal lactic acid bacteria
4. Lactococcus lactis Expressing either Staphylococcus aureus Fibronectin-Binding Protein A or Listeria monocytogenes Internalin A Can Efficiently Internalize and Deliver DNA in Human Epithelial Cells.
5. Surface display of an anti-DEC-205 single chain Fv fragment in Lactobacillus plantarum increases internalization and plasmid transfer to dendritic cells in vitro and in vivo

Currently it has only been developed as an idea, but we expect to continue the project to make it a reality and in a near future generate a vaccine that may help any person who needs it. We are currently talking to different investors that may help this project to go real in the next months, so it can have a great impact in all the population around the world. 

As a goal we does not only want to develop on vaccine, but the complete system, that can be fully characterized and ready for its use against different viruses and diseases.

Finally, in five years we aim to make a business around this idea, that may result a developing diverse solutions for health threats based in genetic engineering, biotechnology and our current delivery system, everything by the name of GENOVA Labs.

The most important barrier is related with the financial area, since the project requires an important amount of money to carry out laboratory investigations, pre-clinical and clinical trials and to scale it globally. It is important to mention, that the final product will be a low cost product, since most of the materials and processes to take it to a large scale are not as expensive as other solutions, but the investment is needed for the previous stages.

 In addition to this, we consider that our knowledge, protocols and ideas are correctly based and the intelectual or technical part does not represent a barrier for anyone of us.

For the barrier discussed above, we have being planning and we are already been talking to different groups and companies that may have interests on supporting our project. Most of them area in our home country, Mexico, but a possible investor is a company from Denmark. We think that the only way of overcoming to this barrier is to talk and share our idea so anyone who may have interest on this kind of projects can be able to help us grow and have the impact that we want to have.

We are a group of Biotechnology Undergraduate Students from ITESM Monterrey in Mexico.

Pedro Chacón Ponce

Alejandro Aguilar García

Salvador García Andrade

Since we are studying biotechnology engineering, we have been developing several skills related not only with critical and scientific thinking, but different laboratory skills. Our whole team is currently involved in research areas in our University, where we obtained our skills and knowledge to develop these ideas. 

Also, we are interested on dedicating to the research area, mainly in health biotechnology and molecular biotechnology. Some of us have been working not only with our University, but with the National Council of Science and Technology (CONACyT), for more than one year.

In addition, we have received tutoring from a group of PhD's to develop this idea, who have given us feedback and advice from their experience.

When we first saw the announcement of Solve MIT we became really excited about the future this could give to our project. Since we all three are biotechnology students interested in doing research as part of our labor lives, we see this program a great opportunity scale up to a bigger level in research. We see a bright future for our project since we have been looking for financial and technical advice in different areas and cities, and we would like to share this project with the world for all the benefits that it can bring to us.

Since we are 3 undergraduate students, we need a team in each of the following categories to help us develop, the business model, the distribution of the vaccine, legal and regulatory matters, etc. Given that we are not yet partnered with experts and this is a relatively new idea, we do not have most of the categories filled, and the bases outside of molecular biology and genetic engineering are not set.

We would like to partner with different organizations and companies no only to obtain financial aid, but experience, exposure and learn from people that have more experience in this areas. Also, we would like to partner for collaborative work with different laboratories and for laboratory equipment.

Some of the companies and organizations are:

1. MIT faculty and initiatives
2. Medical and Biotechnology Schools of partner Universities
3. Thermo Fisher Scientific
4. New England Biolabs
5. Modern Inc
6. Novozymes
7. HellosScience

Given that the solution to this problem is a vaccine for COVID-19 this will allow more than a million people to be benefited, since it will result in the human immunization of the virus, saving countless lives, both the people that are under risk group category and people outside of this.