Nobel Prize in Chemistry will train Brazilian scientists – 10/22/2023 – Science

Idor (Instituto D’Or de Pesquisa e Ensino), linked to Rede D’Or, and IGI (Innovative Genomics Institute), in California, an organization founded by Nobel laureate Jennifer Doudna, formed a partnership to study the editing tool Crispr-Cas9 gene for the treatment of diseases considered to be of concern in Brazil.

The objective of the partnership, whose minimum duration is six years, is to invest in the training of Brazilian professionals abroad — and this is where the training period in Doudna’s laboratory comes in. The application of knowledge about this technique in the country in the health sector is the second stage of the project.

The DNA editing tool was created by the American biochemist together with French researcher Emmanuelle Charpentier. They received the Nobel Prize in Chemistry in 2020 for their discovery.

The finding occurred thanks to the study of the immune system of ancient bacteria and microorganisms. In the technique, the Cas9 enzyme, a nuclease, cuts the two strands of the DNA double helix, making room for the insertion, if applicable, of a new section. Crispr (pronounced “crisper”) is the name of the region of bacterial DNA that has modified parts (in the case of bacteria, obtained from ancient viruses). By bringing the two parts together, the researchers developed a DNA “cut and paste” mechanism.

Its application in science is already known for studies in agriculture, gene editing for the treatment of diseases and also investigated to bring back extinct organisms.

To date, Idor postdoctoral fellows Thyago Leal Calvo, a molecular biologist studying the use of the tool to slow the progression of Alzheimer’s, and Bruno Solano, a physician specializing in cell therapy who is investigating more accessible gene therapies for the treatment of sickle cell anemia , began their internship at IGI, linked to the University of California at Berkeley (USA). Other postdoctoral researchers should also be selected in the coming years.

The collaboration between Idor and IGI is part of Grupo D’Or’s Pioneering Science program, which will invest up to R$500 million in frontier science — interface between basic science, knowledge production, and applied science — for a period of ten years in the country. It is the largest amount ever invested by the private sector in Brazilian science that we know of.

“It is our moral and scientific duty to seek affordable alternatives for the population to advanced therapies. We know that it is important to work on the crest of the wave of knowledge in the area of ​​gene editing therapies and individualized medicine”, says the neuroscientist, creator of Ciência Pioneira and co-founder of Idor, Jorge Moll Neto.

The production of advanced therapies in Brazil is hampered by the high cost of these technologies. “Sometimes, they arrive five or ten years late, at exorbitant prices, making access unfeasible in both the public and private systems. We want to accelerate the development of technologies in our country”, he explains.

So far, the results have been positive, although still incipient. In the case of Solano’s research, the expectation is to file a request for authorization for a clinical trial with Anvisa (National Health Surveillance Agency) by the end of 2024.

Sickle cell anemia is a rare and hereditary genetic condition that affects the function of red blood cells due to a dysfunction of hemoglobin, the molecule responsible for delivering oxygen to cells. “But we can use Crispr to make these cells produce normal hemoglobin in patients with sickle cell anemia”, he explains.

The disease is of special interest in Brazil, a country with a high incidence of sickle cell anemia, with important regional and racial differences: the prevalence is higher in the black population, and the state of Bahia, where the rate is one case for every 650 births alive (compared to one for every 1,200 in the national average), concentrates the majority of cases.

According to Solano, people with sickle cell anemia suffer from severe pain throughout their lives. In the SUS (Unified Health System), treatment is available through bone marrow transplantation, but it depends on the compatibility between donor and recipient. “The advantage of Crispr therapy is precisely being able to use the individual’s own cells in the process”, explains Solano.

“However, cost is a major barrier. In the US, where these therapies await FDA approval [agência que regulamenta drogas e medicamentos], they will have a high cost, of around US$2 million (R$10.1 million). Using the tool changes the expression of fetal hemoglobin, which does not contain the mutation, controlling symptoms. In clinical studies carried out in the USA, patients had a good result. Therefore, we want to seek lower-cost therapies in partnership with IGI,” he said.

Calvo will work on investigating the regulation of a gene that encodes a protein with a neuroprotective function, which could help in therapies for cognitive decline associated with Alzheimer’s. According to him, this protein is naturally expressed in the body and is increased with physical activity. But factors such as age, sedentary lifestyle and other factors reduce its expression. The idea is to use the Crispr tool to increase gene regulation, thus protecting cognitive function.

“This is an application in which there is no modification to the DNA, but rather regulation of the gene aiming to reverse its low expression, generally associated with aging and a sedentary lifestyle, as well as other factors”, he explains.

In the case of Calvo’s research, it is currently in the in vitro phase (in cells modified in the laboratory) and should enter the testing phase with mice. Based on the results of these experiments, you can go through a few more steps before starting tests on humans.

Finally, for Moll Neto, publicizing the partnership is essential to also create an environment for scientific dissemination among the general public. Last week, the IGI research team participated in seminars and debates at Idor in Rio de Janeiro.

“The public needs to be aware of this, we need to take advantage of the space to show the potential and limitations of these technologies, which could help in the treatment of diseases. Frontier and interdisciplinary science has a great impact on society”, he said.