A research team, led by scientists from the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC), has achieved a significant breakthrough in the fight against HIV. The team developed a combination gene therapy that utilizes CRISPR to deactivate or “snip out” two specific genes in “humanized” HIV-positive mice. The study, published in Proceedings of the National Academy of Sciences, showcased impressive results, with approximately 60% of the models being free of the virus, compared to the 29% reported in a 2019 study.
The researchers embarked on their innovative approach by administering long-acting slow-effective release antiretroviral therapy (LASER-ART) to HIV-positive mice. After a month, they utilized the CRISPR-Cas9 gene-editing tool to deactivate the gene responsible for CCR5, a protein that enables the virus to enter and infect cells. Additionally, a second round of CRISPR-Cas9 treatment was employed to remove the integrated copies of HIV-1 DNA from the host genome. The duration of the experiment spanned two months to ensure the virus would not rebound. Ultimately, six out of ten animals in the treatment group achieved freedom from the virus, and five out of nine treated mice in a subsequent round of experiments were completely virus-free.
According to Kamel Khalili, Ph.D., from Temple University, “The importance of this strategy is twofold: First, CRISPR remains the method of choice for permanent elimination of the virus, and second, this combination for targeting the virus along with some other method to prevent spread, such as inactivation of CCR5 by CRISPR, can be improved for permanent elimination of the virus.” The research team aims to enhance the efficacy of the approach and CRISPR technology to achieve the elimination and prevention of the virus’s spread. They are actively working on developing an improved drug delivery system and exploring the potential of targeted nanoparticles and modified viral vectors to deliver HIV-1 gene therapy directly to active growth sites.
Looking ahead, the researchers are optimistic about the future of combination gene editing therapies and are dedicated to advancing their HIV-1 gene therapy. With an ongoing phase 1/2 clinical trial, they strive to refine their approach and gather valuable insights at each step. As Kamel Khalili expressed, “Our next goal is to improve the efficacy of the approach and CRISPR toward the elimination and prevention of the virus’ spread. I think [combination gene editing] is where we need to get to, but we need to learn a little about each step.”
The groundbreaking combination gene therapy using CRISPR and its potential to eliminate HIV in humanized mice holds tremendous promise for the future of HIV treatment and prevention. By pushing the boundaries of scientific innovation, researchers are forging a path towards a world free from the grasp of this persistent virus.