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HIV/AIDS is one of the most devastating pandemics recorded in human history and continues to be a global burden. Since the dawn of this pandemic, it is estimated that around 75 million people have been infected with HIV and around 36 million have died as a result of infection.
Despite advances in knowledge and treatment, there is no vaccine and drugs are not curative. There are several reasons that therapies fail to eliminate the virus from the body, but one particular hurdle is the fact that HIV permanently inserts its genome into our own, a process called integration. The virus is then able to hide away in certain cells, creating what is known as a latent reservoir, replicating at very low levels. As soon as a patient stops taking drugs, replication is kick started. Furthermore, long-term use of toxic anti-HIV drugs can have health consequences. Therefore, in order for treatments to be effective, these reservoirs need to be permanently eliminated, which current regimens cannot succeed in.
In an attempt to tackle this problem, Temple scientists developed a two-stage system to snip out HIV-1 DNA from the host genome. HIV-1 is one of two types of HIV, the other being HIV-2. While both are important, HIV-1 is responsible for the majority of infections worldwide.
The researchers first targeted specific HIV-1 sequences called long terminal repeats (LTRs). These are repetitive DNA sequences located at both ends of the viral genome that are used to insert the HIV DNA into the host genome and also control viral gene expression. They did this by generating highly specific sequences of RNA called guide RNAs (gRNAs). They then used a bacterial nuclease enzyme called Cas9 which snips out the DNA between the two target sequences. This resulted in the complete excision of the HIV-1 DNA from the host cells with no off-target effects on the host genome. Host repair machinery then took over and stuck the DNA strands back together.
They found this to be successful in several different cell lines, including those that are the primary target for HIV. Furthermore, when the researchers added this system to uninfected cells it successfully prevented infection with the virus, indicating it could be used as a preventative measure as well as a treatment.
While the team has a long way to go before this can be used in humans, they believe this could lead to a valid method to cure HIV and are currently working towards preclinical studies. Furthermore, the approach could easily be personalized to suit the unique viral sequences of different patients, and maybe even developed to target other viruses.