Tel Aviv University researchers have published a new study in Nature outlining how a type of white blood cell can be engineered to secrete anti-human immunodeficiency virus (HIV) antibodies. Based on the results of this study, the team are hopeful that they will be able to produce a one-time medication for acquired immune deficiency syndrome (AIDS) and other diseases.
Gene therapy for HIV
The introduction of treatments such as anti-retroviral therapy (ART) for HIV has helped patients diagnosed with the infection to live longer and healthier lives. Patients are required to take the medicine daily in order to reduce the amount of virus in the body (viral load) so that it is undetectable. If a viral load is undetectable, patients with HIV have effectively zero risk of transmitting the virus. However, a one-time treatment for HIV, which can develop into AIDS, is still desirable to improve HIV patients’ quality of life.
Researchers in the laboratory of Dr. Adi Barzel at Tel Aviv University have developed a genetic engineering approach that could provide a solution.
Barzel and colleagues genetically engineered B cells a type of white blood cell, inside the body, enabling them to continuously secrete neutralizing antibodies that act against the virus. “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,” Barzel explains in a news release. “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 coded for the antibody into the B cells in the body.”
Using in vitro methods, they found that the antibodies produced using this genetic engineering approach were effective against HIV. Next, they progressed their work to in vivo models. “All model animals who had been administered the treatment responded and had high quantities of the desired antibody in their blood,” says Barzel.
Using CRISPR for a “one-time” HIV treatment
The genetic engineering was achieved using CRISPR genome editing technology, which enables researchers to target a specific area of the genome using a “molecular search engine” and create cuts in the DNA, to insert or remove specific DNA segments, or genes.
“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,” explains Alessio Nehmad, PhD student in Barzel’s lab and co-author of the study. “We use two viral carriers of the adeno-associated viruses (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."
Genetic-based treatments are not available for HIV currently. Barzel and colleagues believe that their genetic engineering approach offers new opportunities for patients: “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,” Barzel says.
An additional advantage to this methodology is that, should the virus mutate, the B cells will also adapt 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”,” Barzel concludes.
Reference: Nahmad AD, Lazzarotto CR, Zelikson N, et al. In vivo engineered B cells secrete high titers of broadly neutralizing anti-HIV antibodies in mice. Nat Bio. 2022. doi: 10.1038/s41587-022-01328-9.
This article is a rework of a press release issued by Tel Aviv University. Material has been edited for length and content.