“Imagine a single drug that could prevent human immunodeficiency virus (HIV) infection, treat patients who have already contracted HIV, and even remove all the dormant copies of the virus from those with the more advanced disease.” Reading a sentence like that evokes a sense of skepticism, but if the science pans out sometimes you just have to accept it.
Scientists from the Salk Gene Expression Laboratory think that they have found a way to use bacteria’s own defense system in order to chop up HIV virus. When HIV gets into a cell, it will use the cell’s machinery to replicate its genome, but it will also integrate its genome into the host genome. At this point the host turns into a HIV replication factory producing a new HIV genome with every round of meiosis. Current drugs are very effective at targeting specific enzymatic functions in the replication cycle such as the reverse transcriptase, the integrate, and the protease. Despite the highly active antiretroviral therapies that exist, there is no one drug that can target the virus everywhere that it exists, especially the copies buried in the host genome. These copies of the virus stay dormant in the host for years and wait until the host’s immune system is compromised to reactivate.
In response to this challenge a team of researchers turned to bacteria for some answers. Many species of bacteria use a defense system called CRISPR (clustered regularly interspaced short palindromic repeats) to cut up foreign DNA at specific locations. Scientists have been using this technology to edit genes, but Liao and Izpisua Belmonte of the Salk Gene Expression Lab wanted to bring this technology to HIV in a new way. CRISPR uses short nucleic acid sequences called guide RNAs to determine where to cut the DNA. Knowing this the researchers manufactured guide RNA that would allow the system to target specific points in the HIV genome to render the virus nonfunction and non-replication competent. The guide RNAs, CRISPR, and other necessary molecules were added to the immune cells that were infected with HIV, and CRISPR successfully cut the virus at the right spots thereby inactivating the virus entirely. Altogether the virus was chopped up and rendered inactive in 72% of the cells. The great news was that CRISPR chopped up the dormant copies of the virus hidden in the cells’ DNA. While the CRISPR had been used to the same effect is previous work, these researchers showed that this system worked best on active, full length virus rather than inactive, shortened sequences of the virus. The researchers value their findings, but they are looking to use this technology in a prophylactic sense. Izpisua Belmonte says, “By eliminating the virus at the early steps of its life cycle, we can altogether prevent the infection of human cells in an analogous manner to how conventional vaccines work.” If these researchers or anyone developed the this technology it would drastically change the history of virology, but only more time, more money, and more research can tell.
- Nalani Wakinekona