Transplantation of B cells engineered ex vivo to secrete broadly neutralizing antibodies has shown efficacy in disease models.
The technology has been used to turn off unwanted genes or repair and insert wanted genes. Photo: Shutterstock.
The research was revealed in Nature Biotechnology, indicating that this new and unique AIDS treatment that can be turned into a vaccine for patients with HIVwhere after examining the engineering of type B white blood cells in the patient’s body to secrete anti-HIV in response to the virus.
The researchheld at Tel Aviv University (Israel), was directed by Adi Barzel Y doctoral student Alessio Nehmad, both from the George S. Wise School of Life Sciences School of Neurobiology, Biochemistry and Biophysics and the Dotan Center for Advanced Therapies, in collaboration with Sourasky Medical Center. The study was conducted in collaboration with additional researchers from Israel and the US.
The technique developed in his laboratory uses type B white blood cells that would be genetically modified within the patient’s body to secrete neutralizing antibodies against the virus HIV that causes the disease. B cells are a type of white blood cell responsible for generating antibodies against viruses, bacteria, and more. B cells are made in the bone marrow. When they mature, B cells pass into the blood and lymphatic systems and from there to different parts of the body.
“Until now, only a few scientists, and us among them, had been able to engineer B cells outside the body, and in this study we were the first to do it in the body and make these cells generate desired antibodies Genetic engineering is done with carriers viral derivatives of viruses that were designed not to cause harm but only to deliver the gene encoding for the antibody to B cells in the body,” Barzel says.
Furthermore, he adds, “in this case we were able to precisely introduce the antibodies to a desired site in the B cell genome. All the model animals that had been given the treatment responded and had large amounts of the desired antibody in We produced the antibody from the blood and made sure that it was actually effective in neutralizing the virus of the HIV in the lab dish.
Gene editing was done with a CRISPR. This is a technology based on a bacterial immune system against viruses. Bacteria use CRISPR systems as a kind of molecular “search engine” to locate viral sequences and cut them to inactivate them. Two biochemists who had discovered the sophisticated defense mechanism, Emmanuelle Charpentier and Jennifer Doudna, were able to divert the route to cleavage of any DNA of their choosing.
Since then, the technology has been used to turn off unwanted genes or repair and insert wanted genes. Doudna and Charpentier gained international recognition when they became winners of the 2020 Nobel Prize in Chemistry.
They incorporated the ability of a CRISPR to direct the introduction of genes to desired sites along with the abilities of viral carriers to deliver desired genes to desired cells. Therefore, we can engineer the B cells inside the patient’s body.
“We used two viral carriers from the AAV family, one carrier codes for the desired antibody and the second carrier codes for the CRISPR system. When CRISPR cuts at the desired site in the B cell genome it directs the introduction of the desired gene: the gene encoding the antibody against the virus HIVwhich causes AIDS,” says Alessio Nehmad.
Currently, the researchers explain, there is no genetic treatment for AIDS, so the opportunities for research they are huge. “We developed an innovative treatment that can defeat the virus with a single injection, with the potential to make a huge improvement in patients’ condition. When the engineered B cells encounter the virus, the virus stimulates them and encourages them to divide.” , so we’re using the very cause of the disease to fight it,” says Barzel.
Furthermore, “if the virus changes, the B cells will also change accordingly to fight it, which is why we have created the first drug that can evolve in the body and defeat viruses in the ‘arms race.’
Over the last two decades, the lives of many AIDS patients have improved as a result of the administration of treatments that change the disease from fatal to chronic. However, there is still a long way to go before a treatment is found that will provide patients with a permanent cure. One possible way to do this would be with a single injection, which is starting to take shape in Barzel’s lab.
Based on this study, “we can hope that in the next few years we will be able to produce a drug for AIDS, for other infectious diseases and for certain types of cancer caused by a virus, such as cervical cancer, cancer of the head and neck and more,” he concludes.
Source consulted here.