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A team from Tel Aviv University has developed a treatment for HIV that involves genetically modifying immune cells directly in the patient’s body, so that the appropriate antibody is produced. This innovative approach, based on the CRISPR-Cas9 tool, will make it possible to treat people infected with HIV with a single injection.
HIV infection is now relatively well managed. The antiretroviral drugs given to patients significantly reduce virus replication and allow their immune system to continue to function. However, this approach does not completely eliminate the virus, which remains in a latent form in the body. Therefore, treatment must be taken for life, which is accompanied by undesirable effects such as increased risk of cardiovascular disease, impaired kidney and liver function, or even osteoporosis.
In addition, many ARVs are a source of ADRs (particularly with some antibiotics or contraceptives). So researchers are actively working to develop a treatment that offers patients a permanent cure, so that they can return to a completely normal life. Dr. Berzel’s laboratory at Tel Aviv University may be on the way: he and his team have developed a treatment based on genetically modified B lymphocytes He lives.
Antibody to HIV secreted by B cells
B lymphocytes, or B cells, are a type of circulating white blood cell, which produces antibodies capable of detecting and neutralizing pathogens in a certain way. They form in the bone marrow and then travel through the blood and lymphatic system where they can reach all parts of the body.
Several studies have already shown that transplantation of modified B cells outside of vivo Secretion of highly neutralizing antibodies can be very effective against certain diseases, including HIV infection. The Prezel team had already successfully tested this method themselves. However, as the researchers pointed out in their study, the clinical translation of this approach requires specialized medical centers and protocols that technically and above all require full compatibility between donor and recipient cells.
So Berzel and his colleagues came up with the idea of modifying B cells He livesdirectly into the patient’s body. Their approach is based on the CRISPR-Cas9 gene-editing tool; The researchers used two viral vectors derived from viruses – one encoding for Staphylococcus aureus Cas9 (saCas9) and the other for an anti-HIV antibody, called 3BNC117. These vectors have been modified to be harmless to the organism, but capable of introducing the genetic coding for HIV antibodies into B cells.
This treatment was tested on mice: all of those who received an intravenous injection of the compound had high amounts of the required antibody in their blood. The team reported a neutralization titer of up to 6.8 µg/mL.
Treatment that can be applied to other infectious diseases
” We were able to precisely insert the antibodies into the desired location of the B cell genome ”, confirms Dr. Berzel in a press release. As mentioned earlier, the gene editing was performed using the CRISPR-Cas9 system, which allows DNA to be cut at a very precise location in the genome, in any cell.
Cas9 – derived here from Staphylococcus aureus – is actually a protein of bacterial origin with antiviral properties, capable of cutting the virus’ DNA at specific sequences to neutralize it. CRISPR-Cas9 technology, developed by Emmanuel Charpentier and Jennifer Doudna, is widely used today to disrupt unwanted genes or, conversely, to repair or insert genes.
Here the researchers exploited the ability of CRISPR-Cas9 to direct gene insertion to desired sites, as well as the capabilities of viral vectors to deliver appropriate genes to target cells. This is how they genetically modified B cells He lives. The team also reported “minimal off-target division” of the cell’s DNA. When the modified B cells encounter the virus, they are stimulated and divide so that they can better fight it. ” Moreover, if the virus changes, the B cells will also change accordingly to fight it. That is why we created the first drug capable of developing in the body Dr. adds. Brzel.
engineering He lives Therefore it appears that B cells for therapeutic antibody expression is a safe, robust and scalable method. It can be applied not only to infectious diseases, but also to the treatment of non-communicable diseases, such as cancer and autoimmune diseases. This innovative treatment, which is able to eliminate the virus with a single injection, can improve the quality of life for people living with HIV. Researchers hope to develop an anti-AIDS drug in the coming years. According to the Joint United Nations Program on HIV/AIDS, 37.7 million people worldwide were infected with HIV in 2020.
Source: A. Nahmad et al., Nature Biotechnology
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