A "genomic word processor" with the possibility of making HIV/AIDS a thing of the past

Scientists may have found a new treatment for one of the most threatening worldwide epidemics, AIDS. Acquired immunodeficiency syndrome, or more commonly known as AIDS, has been affecting humans since it was first clinically observed in 1981 and later discovered in 1983. Scientists have spent decades studying AIDS and have come to know HIV-1, the clever virus behind the scenes, well. The tactics this virus employs continue the long-fought battle between leading scientists and this worldwide epidemic. The interest of scientists continues to be captured by this disease and has stumped the world’s leading investigators in developing a cure for AIDS. Until now.

VIRAL TACTICS + MEDICINE’S BEST WEAPON TODAY

It’s no secret that the research and development invested in the discovery of a cure for AIDS is pertinent, and even necessary. New infections continue to arise at alarming rates, reaching more than two million cases per year. Viruses infect host cells, such as those of an AIDS patient, and essentially high-jacks the cell’s machinery to stay alive and reproduce by injecting and incorporating its own viral DNA into the genome of the host. If we stepped into the arsenal that modern medicine has to fight with, antiretroviral therapy (ART) would be the weapon of choice in the battle against HIV/AIDS. This treatment has been successful in effectively controlling the number of viruses in the bloodstream in essentially all HIV-1 patients studied and has also been shown to partially restore important host cells, CD4+ T-cells. These are a type of white blood cell that play a key role in protecting the body from invaders, such as viruses, by activating an immune response. ART is fairly effective, however, it still must confront one last shortcoming: it fails to eliminate HIV-1 from latently-infected T-cells. This unique population of T-cells has been infected by the HIV-1 virus but its infection is dormant, meaning symptoms or signs of its infection are not readily seen, rather the virus is waiting to attack at any moment. A new possible treatment scientists have recently developed may be equipped to overcome this hurdle in the race towards finding a cure for AIDS.

OBSTACLES MEDICINE STILL FACES

In latently-infected T-cells, these viral DNA copies lie dormant in the cell but are capable of being reactivated to produce the virus when these T-cells are activated. This results in a rapid viral “rebound” during treatment with ART, requiring AIDS patients to maintain life-long therapy, an expensive and taxing course of action. These T-cells act like AIDS reservoirs and are believed by scientists to be the most prominent cell pool of AIDS in the body. Consequently, they have caught the attention of cutting edge research aimed at eliminating latent HIV-1 infection.

As of early 2016, efforts to eradicate HIV-1 from these T-cells have typically followed a “shock and kill” approach. This involves inducing HIV reactivation in these cells to trigger elimination of virus-producing cells by bursting these cells open, rendering them destroyed, or by tapping into the host immune response. However, there remain numerous problems with this approach: (1) not all viral DNA in the host cells can produce the virus, (2) the number of T-cells reactivated in this way is significantly less than the total number of T-cells infected, (3) the immune response that is activated is often not sufficient to eliminate the virus, and (4) uninfected, healthy T-cells are not protected from this induced HIV infection and can therefore be at risk for infection. These remaining obstacles beg the question: how exactly can this cell population be combatted? A team of scientists at Temple University picked up their centrifuge tubes and micropipettes to answer this question.

A PROMISING AIDS TREATMENT

Dr. Kaminski and his team postulated that an effective cure tactic for HIV-1 infection should employ a way to eliminate the viral genome from HIV-1-positive cells, including the previously discussed CD4+ T-cell population, while protecting healthy cells from future HIV-1 infection with minimal harm to the host. To tackle this, Kaminski and his team utilized clustered, regularly-interspaced, short palindromic repeats (CRISPR)/Cas9 genome editing technology. The underlying biology behind CRISPR/Cas9 is fascinating, and complex, but essentially boils down to a system of bacterial DNA and proteins capable of editing genomes like a word processor. CRISPR DNA sequences are key pieces of the bacterial immune system responsible for protecting the organism. If a threat is detected, such as a viral infection, the CRISPR/Cas9 system can attack the invader by destroying the genome of the virus. This is an effective tactic because the genome of the virus that CRISPR targets is necessary to produce proteins and other molecules necessary for the virus to survive. Therefore, destroying the viral genome kills the virus and protects the host from invasion. This elegant system can also introduce new genes, remove old ones, or even change current gene sequences. This technology has been studied in a wide range of commonly employed animal models, from mice to yeast to fruit flies, and is now being applied to the realm of human disease.

Kaminski and his team modified the CRISPR/Cas9 system to recognize HIV-1 viral DNA sequences necessary for the survival of the virus and programed it to essentially cut out these viral sequences that have been integrated into latently HIV-1-infected human T-cells. The team was successful in eliminating viral DNA fragments in latently-infected T-cells without causing harm to the host. Additionally, they were able to observe a significant amount of suppression, which suggests that not only can this CRISPR/Cas9 system eliminate viral DNA, but it can also reduce expression of already active copies of this DNA. The results of this study open the door to an incredibly promising therapeutic treatment to eliminate HIV-1 from this cell population and to ultimately prevent the daunting recurrence of AIDS.

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