Scientists successfully eradicate HIV-1 DNA from human T cells, using advanced gene editing technology

Scientists Successfully Eradicate HIV-1 DNA From Human T Cells-3

Scientists at Temple University are working on a highly-specialized gene editing technology that could one day serve as a cure for AIDS. As part of a new research, the team has successfully eliminated the infection-causing virus from the DNA of host cells, grown in the laboratory. The findings of the study were recently published in the Scientific Reports journal.

Human immunodeficiency virus (HIV) is known to attack the patient’s immune system, weakening it systematically and resulting in a condition called acquired immune deficiency syndrome (or AIDS). Since the first case was reported back in 1980s, HIV/AIDS has killed as many as 25 million people, primarily in the Sub-Saharan region of Africa. Although technological advances in recent years have made its treatment and management more efficient, there is sadly no cure for the condition.

Scientists Successfully Eradicate HIV-1 DNA From Human T Cells-2

Up until now, attempts to extirpate the virus after it has infected CD4+ T-cells has proven extremely difficult. One major line of research focuses on intentionally reactivating the deadly pathogen, as a way of kickstarting the body’s own immune response. Such attempts, however, have largely remained unsuccessful. Speaking about the condition, Kamel Khalili of the university’s Lewis Katz School of Medicine (LKSOM) said:

Antiretroviral drugs are very good at controlling HIV infection. But patients on antiretroviral therapy who stop taking the drugs suffer a rapid rebound in HIV replication.

For the current research, the scientists adopted a different approach, aimed at targeting the specific HIV-1 proviral DNA (basically, the core viral genetic material). To do that, the researchers took the help of an advanced gene editing technology. According to the team, the system comprises of a guide RNA that helps locate the HIV-1 DNA in the host’s T-cell genome. Additionally, it relies on a nuclease enzyme to snip the strands of the T-cell DNA.

Scientists Successfully Eradicate HIV-1 DNA From Human T Cells-1

The enzyme working by carefully cutting out the HIV-1 DNA sequence, following which the loose ends of the host genome are stitched together by the cell’s innate DNA repairing tehcnique. The team had previously tested the efficacy of the technology in eliminating the virus’ DNA from human cell lines. In the new study, the scientists focused their efforts on treating HIV-infected CD4+ T cells. As the researchers point out, the system is capable of effectively killing the pathogens from the cells, while also preventing reinfection.

For the purpose of testing, the group grew human cells infected with HIV in culture. When treated with the help of the newly-developed gene editing system, the cells exhibited a significant decrease in viral load and replication. To check if the technology caused any kind of toxicity, the researchers analyzed the genetic material of the HIV-1-eliminated cells using a specialized technique known as ultra-deep whole-genome sequencing.

As the team points out, the T cells that underwent treatment showed no evidence of abnormal genetic mutation. Cell vitality and proliferation also showed marked improvement. Khalili added:

The findings are important on multiple levels. They demonstrate the effectiveness of our gene editing system in eliminating HIV from the DNA of CD4 T-cells and, by introducing mutations into the viral genome, permanently inactivating its replication. Further, they show that the system can protect cells from reinfection and that the technology is safe for the cells, with no toxic effects. These experiments had not been performed previously to this extent. But the questions they address are critical, and the results allow us to move ahead with this technology.

Source: Temple University

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