TAU researchers offer future AIDS treatment in one shot | The Jewish Press – JewishPress.com | Jewish Press News Bureau | 15 Sivan 5782 – June 13, 2022

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A new study from Tel Aviv University suggests a new and unique AIDS treatment that could be developed into a vaccine or a one-time treatment for HIV patients.

The study looked at the engineering of type B white blood cells in the patient’s body to secrete HIV antibodies in response to the virus. The study was led by Dr. Adi Barzel and Ph.D. student Alessio Nehmad, both of the School of Neurobiology, Biochemistry and Biophysics at the George S. Wise School of Life Sciences and the Dotan Center for advanced therapies in collaboration with Sourasky Medical Center (Ichilov). The study was conducted in collaboration with other researchers from Israel and the United States. The study was published in the prestigious journal Nature (In vivo-modified B cells secrete high titers of broadly neutralizing HIV antibodies in mice).

Over the past two decades, the lives of many AIDS patients have improved through the administration of treatments that turn the disease from life-threatening to chronic. However, we still have a long way to go before we find a treatment that would provide patients with a permanent cure. A possible way to do this, with a single injection, was first developed in Dr. Barzel’s lab. The technique developed in his laboratory uses type B white blood cells which would be genetically modified inside the patient’s body to secrete neutralizing antibodies against the HIV virus which causes the disease.

B cells are a type of white blood cell responsible for producing antibodies against viruses and bacteria. B cells form in the bone marrow. As they mature, B cells travel through the blood and lymphatic system and from there to different parts of the body.

Dr. Adi Barzel / Tel Aviv University

Dr Barzel explains: “Until now, only a few scientists, and we among them, have been able to engineer B cells outside the body, and in this study, we were the first to do so in the body and making these cells generate the desired antibodies. Genetic engineering is done with viral carriers derived from viruses that have been engineered to not cause harm, only to deliver the gene coded for the antibody into the body’s B cells. Additionally, in this case, we were able to precisely introduce the antibodies into a desired site of the B cell genome. All model animals that received the treatment responded and had large amounts of the desired antibody in their blood. We produced the antibody from the blood and made sure that it was really effective in neutralizing the HIV virus in the lab box.

Gene editing was performed with CRISPR (acronym for clustered regular interspaced short palindromic repeats). It 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 out in order to deactivate them. Two biochemists who had understood the sophisticated defense mechanism, Emmanuelle Charpentier and Jennifer Doudna, were able to reorient themselves for the cleavage of any DNA of choice. The technology has since been used either to turn off unwanted genes or to repair and insert desired genes. Doudna and Charpentier gained international recognition when they became winners of the Nobel Prize in Chemistry in 2020.

Alessio Nehmad / Tel Aviv University

PhD student Alessio Nehmad explains the use of CRISPR: “We incorporate the ability of a CRISPR to direct the introduction of genes into the desired sites as well as the abilities of the viral carriers to deliver the desired genes to the desired cells. So we can engineer the B cells inside the patient’s body. We use 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 the desired site in the B cell genome, it directs the introduction of the desired gene: the gene coding for the antibody against the HIV virus, which causes AIDS.

Currently, the researchers explain, there is no genetic cure for AIDS, so the research opportunities are vast. Dr Barzel concludes: “We have developed an innovative treatment that can defeat the virus with a single injection, with the potential to bring about a considerable improvement in the condition of patients. When the modified B cells encounter the virus, the virus stimulates them and encourages them to divide, so we use the very cause of the disease to fight it. Moreover, if the virus changes, the B cells will also change accordingly in order to fight it, so we have created the first medicine that can evolve in the body and defeat viruses in the “arms race”.

Based on this study, we can expect that in the years to come we will be able to produce drugs in this way for AIDS, for other infectious diseases and for certain types of cancer caused by a virus, such as cervical cancer, head and neck cancer. , and more.”

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