Scientists who re-wrote the code of life win the Nobel Prize in Chemestry

Thanks to this method, it has been possible to cure or mitigate diseases of genetic origin, such as some types of cancer and hereditary diseases such as hypertrophic myocardiopathy

A historical achievement. This is how we can describe the technique discovered by Emmanuelle Charpentier, director of the Max Planck Institute of Infection Biology, and Jennifer A. Doudna, biochemist at the University of California Berkeley, known as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). Certainly when they discovered the technology, in 2012, Charpentier and Doudna could not imagine that they would go down in history for being the first women to win the award together. The Nobel 2020 in Chemistry was presented to researchers on October 7.

The method of editing the genome called CRISPR is a very simple and powerful tool that allows scientists to alter in a minimally invasive way the DNA of animals, plants and microorganisms with extreme precision. As a kind of genetic scissors, the technique allows to cut a specific part of the DNA, causing the cell to produce or not certain proteins. This technology has a revolutionary impact on the biological sciences and has contributed to the treatment of hereditary diseases, such as hematological diseases and cancer, and can make the dream of cure a reality.

It is no exaggeration to say that the technique discovered by researchers has revolutionized the area. While it has immense potential to transform our lives, the technique has raised many ethical questions. In an interview with the Communications Office of the Brazilian Society of Tropical Medicine (SBMT), Dr. Doudna recognizes that the ability to edit the human genome has an immense potential to cure genetic diseases. So much so that we are already seeing positive results with CRISPR-based therapies against blood diseases such as anemia and beta thalassemia. I have no doubt that we will see more advances against genetic diseases very soon, and we are still in the first days of this line of research, she highlights.

But the Nobel laureate admits that the greatest ethical concerns are related to reaching genome editing where changes are passed from one generation to another. At this moment, we are simply not prepared to edit human embryos safely yet, and there is much we still dont understand about the social and cultural impacts of doing so. The good news is that scientists and governments have been talking openly about these issues so that we can establish the appropriate international guidelines. Hopefully, well have so much to do to treat people with genetic diseases in ways that are no longer hereditary, so we have a lot of work ahead of us that can help many people in the years to come, Doudna says.

The researcher also draws attention to an area that may not be as remembered as the genomic edition: agriculture. Genomics editing therapies can help people, but also crops, making them more resistant to diseases and resilient to the effects of climate change, which can have a much larger scale effect. Clearly there are also ethical considerations to this, including preserving cultural heritage and regional varieties of crops, but I believe we will also see a major impact on human health from genomics publishing in agriculture, concludes the 2020 Nobel Prize winner for chemistry.

The winners who discovered one of the sharpest tools of genetic technology are now part of the select group of just seven women who have already received the honor – compared to 178 men. Before Charpentier and Doudna, the five women who won the Nobel Prize in Chemistry were: Marie Curie (1911), Irène Joliot-Curie (1935), Dorothy Crowfoot Hodgkin (1964), Ada E. Yonath (2009) and Frances H. Arnold (2018). The American poet Louise Glück was the winner of the Nobel Prize for Literature 2020.

Application and hopes of CRISPR/cas9 technology in tropical diseases

For Dr. Angela Kaysel Cruz, Professor of the Department of Cellular and Molecular Biology of the Medical School of Ribeirão Preto of the University of São Paulo (FMRP-USP), who works in the area of Molecular Biology/Genetics of the protozoan parasite Leishmania, the application of the CRISPR-Cas9 system for each new organism represents a technical challenge, but the successful experience with different organisms, from unicellular to more diverse and distant metazoa in the evolutionary scale, suggests that the challenges are transposable without difficulties.

The professor explains that all this revolution represented by the domain of CRISPR-Cas9 as a tool, originated from the knowledge acquired in pure scientific research, basic science, when some creative minds knew how to transform what nature already executes in technology – a powerful technology – for its reach, apparent universality, speed and efficiency. What is observed and expected for the next years is a great acceleration in the advance of knowledge in cellular, biochemical and genetic functioning of the most diverse organisms, before the possible practical and great applications, she adds.

CRISPR-Cas9 is a cheaper, simpler and easier to use technique than others. Besides, it is easy to handle, does not require the use of expensive equipment and reagents, that is, there are great advantages in using the CRISPR-Cas9 system of genome editing if we compare it to the technologies and approaches for genome editing that we have mastered until now. The apparent ease of adaptation of CRISPR-Cas9 system to the most diverse organisms is one of these advantages, but its efficiency, speed, its biggest advantage.

In less than a decade after being described, the technique has been adapted for use in various organisms including various human parasites. There are reports describing the deletion or modification of several sets of genes in protozoan species such as Trypanosoma, Leishmania, Plasmodium, Toxoplasma, Cryptosporidium, Trichomonas vaginalis or helminths such as Schistosoma, Strongyloides and Brugia; all of them important human pathogens. In association with the advances with the adaptation of the system to parasites such as those mentioned, also for some vectors of these diseases, such as Anopheles, the editing system has been used successfully, recalls Dr. Cruz.

The professor clarifies that the efficiency of this editing system has shown itself to be very high, and in different parasites it has already been demonstrated that it is possible to obtain the knockout of all alleles of genes in an experimental stage, or even the knockout of several copies of multigenic families, also in a single stage. Using Leishmania as an example to point out the advance that represents the genomic edition by the CRISPR-Cas9 system, we remember that since the beginning of the 1990s, therefore along almost three decades, the knockout of approximately 200 genes were reported, accompanied by the functional studies of these knockout parasites. In this period, the gene knockout was done by homologous recombination, which although it was efficient and safe, required that each allele was replaced in sequential stages and included several procedures of molecular cloning, so that several months were necessary to obtain the deletion or editing of a given gene in the genome of the parasite to then start functional studies, he emphasizes.

Also according to Dr. Cruz, in the period prior to the use of Cas9, the articles often presented the deletion of a gene and its effects. The studies conducted using CRISPR-Cas9 technology may contain hundreds of genes that, for example, compose a certain pathway or that represent the diversity of protein families. These large scale approaches allow a better understanding of the processes and their complexities in a more global way. Thus, once understood the interactions and interrelationships between gene products and their roles in the development of the parasite it will be safer and more assertive to interfere in the progress of the parasite and its establishment in the host. It is possible to glimpse the generation of attenuated parasites effectively, which can be examined as live and safe vaccines, as is desired in the case of leishmaniasis, for example. It is also possible to speculate that there will be a rapid increase in the number of proteins identified as potential targets for drugs, he acknowledges by justifying that it is his understanding that particularly rapid gains will be achieved in the search for vaccines and in the rational design of leading compounds for the development of more effective and less toxic drugs against human parasitic diseases.