The technology also has the potential to be developed into a cure for AIDS
A new study from Tel Aviv University proposes a novel AIDS treatment that could be turned into a vaccine or a one-time treatment for HIV patients. The research explored modifying type B white blood cells in the patient’s body to release anti-HIV antibodies in response to the virus. Dr. Adi Barzel and Ph.D. student Alessio Nehmad led the study, which was conducted in partnership with the Sourasky Medical Center (Ichilov), the George S. Wise department of life sciences, and the Dotan Center for Advanced Therapies. The study was carried out in cooperation with other researchers from Israel and the United States. The findings were published recently in the renowned journal Nature Biotechnology.
Many AIDS patients’ lives have improved during the past two decades as a result of the administration of medicines that have transformed the condition from fatal to chronic. However, we have a long way to go before finding a medication that can offer patients a permanent cure. Dr. Barzel’s laboratory pioneered one feasible method, a one-time injection. His team devised a technology that employs type B white blood cells that are genetically altered within the patient’s body to release neutralizing antibodies against the HIV virus, which causes the disease.
B cells are white blood cells that produce antibodies against viruses, bacteria, and other pathogens. Bone marrow is where B cells are formed. When they mature, B cells move into the blood and lymphatic system and from there to the different body parts.
Dr. Barzel explains: “Until now, only a few scientists, and we among them, had been able to engineer B cells outside of the body, and in this study, we were the first to do this in the body and to make these cells generate desired antibodies. The genetic engineering is done with viral carriers derived from viruses that were engineered so as not to cause damage but only to bring the gene coding for the antibody into the B cells in the body. Additionally, in this case, we have been able to accurately introduce the antibodies into a desired site in the B cell genome. All model animals who had been administered the treatment responded and had high quantities of the desired antibody in their blood. We produced the antibody from the blood and made sure it was actually effective in neutralizing the HIV virus in the lab dish.”
The genetic editing was done with CRISPR. This is a technology based on a bacterial immune system against viruses. The bacteria use the CRISPR systems as a sort of molecular “search engine” to locate viral sequences and cut them in order to disable them. Two biochemists who had figured out the sophisticated defense mechanism, Emmanuelle Charpentier and Jennifer Doudna, were able to reroute for the cleavage of any DNA of choice. The technology has since been used to either disable unwanted genes or repair and insert desired genes. Doudna and Charpentier earned international recognition when they became chemistry Nobel Prize winners in 2020.
Ph.D. student Alessio Nehmad elaborated on the use of CRISPR: “We incorporate the capability of a CRISPR to direct the introduction of genes into desired sites along with the capabilities of viral carriers to bring desired genes to desired cells. Thus, we are able to engineer the B cells inside the patient’s body. We use two viral carriers of the AAV family, one carrier codes for the desired antibody, and the second carrier codes the CRISPR system. When the CRISPR cuts in the desired site in the genome of the B cells 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 treatment for AIDS, so the research opportunities are vast. Dr. Barzel concludes: “We developed an innovative treatment that may defeat the virus with a one-time injection, with the potential of bringing about tremendous improvement in the patients’ condition. When the engineered B cells encounter the virus, the virus stimulates and encourages them to divide, so we are utilizing the very cause of the disease to combat it. Furthermore, if the virus changes, the B cells will also change accordingly in order to combat it, so we have created the first medication ever that can evolve in the body and defeat viruses in the ‘arms race’.”
He continues, “Based on this study we can expect that over the coming years we will be able to produce in this way a medication for AIDS, for additional infectious diseases and for certain types of cancer caused by a virus, such as cervical cancer, head, and neck cancer and more”.
Reference: “In vivo engineered B cells secrete high titers of broadly neutralizing anti-HIV antibodies in mice” by Alessio D. Nahmad, Cicera R. Lazzarotto, Natalie Zelikson, Talia Kustin, Mary Tenuta, Deli Huang, Inbal Reuveni, Daniel Nataf, Yuval Raviv, Miriam Horovitz-Fried, Iris Dotan, Yaron Carmi, Rina Rosin-Arbesfeld, David Nemazee, James E. Voss, Adi Stern, Shengdar Q. Tsai and Adi Barzel, 9 June 2022, Nature Biotechnology.