Like other retroviruses, the genetic material of HIV lodges itself in the genome of its human host. While antiviral therapies are effective at repressing HIV, they do not remove the integrated virus. However, in a recent study published by Proceedings of the National Academy of Sciences of the United States of America (PNAS), researchers and scientists found a new method that effectively deletes HIV from human cells for the first time in history.
The scientific researchers at Temple University, led by Kamel Khalili, utilized the CRISPR/Cas9 genome-editing system. The system removes the disease cells from varying human cell lines. They target the both the 5′ and 3′ ends of the virus, named the long terminal repeats, so that the entire viral genome is deleted.
Khalili stated that he was overjoyed with the result of his experiments. He explained that he was perplexed that the system could correctly identify a single copy of the HIV virus in the chromosome and remove that section, and only that section. His team also discovered that not only could Cas9 excise one copy of the HIV genome, but while operating within the same cell, it can delete another copy in a different cell. Additionally, Khalili reported that the gene-editing method prevented subsequent infections.
The work is a continuation of a study published last year by Yoshio Koyanagi and his colleagues at Kyoto University that utilized the same Cas9 system. Koyanagi declared that Khalili had improved on the technology his team experimented with and developed a more effective, efficient, and precise system.
The one limitation to the new method that scientists have found to delete HIV cells is that the operation is capable of deleting unintended parts of the genome. Khalili stated that his team solved this issue when they presented their findings which revealed there were no off-target effects on the cells they used the system on. T.J. Cradick, the director of protein engineering at Georgia Tech University, said that a more thorough analysis of potential off-targets needs to be examined before the HIV deletion technology is prudent to ensure that nothing is overlooked.
Cradick did state, even though he had no participation in the study, that the deletion method utilized at Temple University is very exciting and the most promising development in curing the disease. Koyanagi is developing a new method with the system that does not delete latent cells, but rather “flushes” them out. The Kyoto University team has not yet released any details regarding their progress on their new development.
The challenge that is facing Khalili now is delivery. Infected cells are one in a million according to the scientific researcher. It is difficult to implement gene editing therapies that can effectively find the disease cells. His group is looking to solve this issue via a nanoparticle delivery system, and he hopes to test it on a mouse model as soon as possible. They are currently seeking additional funding so they can continue to develop their new technology and hope to implement it into hospitals as soon as possible.
By Andres Loubriel