Ural Federal University: Ural Scientists Develop Technology to Correct Genetic Defects

Scientists at the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences and UrFU develop methods for genetic diagnosis and therapy of diseases caused by primary immunodeficiency. This is a congenital malfunction of one or more parts of the immune system that predisposes to the development of frequent, prolonged, hard-to-treat diseases, not only infectious but also autoimmune, autoinflammatory and oncological diseases. For example, systemic lupus erythematosus, various vasculitis, chronic pneumonia, and even hair loss.

Today, primary immunodeficiencies are treated with replacement therapy and hematopoietic stem cell transplantation. However, the treatment of such diseases promises to become more effective by replacing genetic defects in human DNA. Mikhail Bolkov, a Senior Researcher at the Department of Immunochemistry of Ural Federal University and the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, spoke about this on the air of Radio “Komsomolskaya Pravda”.

“More than 500 molecular genetic defects that affect the immune system have now been described. We know that about 2% of the world’s population suffers from immune system-related diseases in one way or another, but they do not know what causes their disease. They visit different doctors, but they cannot find the cause, because they do not know that they have a genetic predisposition, a disorder in the genome. That is why we are engaged in genetic diagnostics, looking for abnormalities in the immune system and corresponding DNA sequences, and our colleagues around the world are developing cell modification technology to replace the abnormal gene sequence with the correct one,” notes Mikhail Bolkov.

CRISPR-Cas9 technology was discovered because of what was learned about immunity in bacteria. They have CRISPR genes, with the help of which they memorize a virus fragment in their DNA, and because of Cas they cut the genome of the virus that entered the bacterium, so therapy of bacterial infections with bacteriophages (bacterial viruses) is not always effective. Scientists have learned how to use the CRISPR-Cas9 system by specifying a target region of the human genome to target instead of a virus fragment. As a result, mutations and errors in the genome can be corrected, and modern treatments for genetic diseases, including congenital immunity errors or primary immunodeficiencies, will be based on this.

“Therefore, our task is to fix this disruption in the cell, to make a “patch” in place of the genetic defect. To do this, we take an enzyme that protects bacteria from viruses and recognizes the nucleic acid sequences in the RNA of the virus. We give the enzyme a marker for the right place in the DNA, and it cuts the DNA in the right place, from where we cut out the damaged portion of the genome and insert the correct one,” adds Mikhail Bolkov.

Now the technologies for modifying genetic diseases are under development and testing. The testing process is very long, starting with the testing of a single cell, scientists then transfer the treatment process to animals. As Mikhail Bolkov explains, treatment of humans with such technologies is not yet available, but expensive operations to treat complex diseases will become possible in the next few years.