Ellie Teng ‘21

The human immunodeficiency virus type one (HIV-1) is responsible for infecting millions worldwide. Currently, antiretroviral therapy (ART) is being used to slow HIV progression; however, as soon as this treatment is stopped, HIV-1 is reactivated and progresses to acquired immunodeficiency syndrome (AIDS). The reactivation of HIV-1 following the cessation of ART is as a result of the virus’ ability to integrate its DNA into the genomes of immune system cells. There, it becomes dormant and undetectable. In a recent breakthrough, scientists from the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC) were able to eliminate HIV-1 from animal genomes. 

Sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 were used to remove the virus in dormant infectious reservoirs in HIV-1 infected humanized mice. LASER ART maintains effective antiretroviral drug concentrations in blood and tissue viral reservoirs from days to weeks. As successful as it is alone, LASER ART cannot eliminate HIV-1 by itself as the virus will still be present in the gut, lymph nodes, brain, spleen other tissue due to long term infections in CD4 and memory  T cells. Thus scientists combined LASER ART and CRISPR-Cas9 to specifically and efficiently excises fragments of integrated HIV-1 proviral DNA from the host genome. For HIV to be eliminated, a number of conditions must be met: ART delivery must be precise, immune control maintained, and viral growth stopped. To test if HIV was really eradicated from the genome, researchers conducted tests such as viral gene amplification, adoptive viral transfers, and on target and off target assessments. 

Mice who had been infected with HIV-1 was treated with LASER ART and CRISPR-Cas9, and further testing found the mice genomes to be free of the HIV-1 virus. Together, LASER ART and CRISPR-Cas9 can provide a permanent cure for those afflicted by HIV. It is possible that soon this treatment will be modified to finally cure HIV in humans.

References:

1. P. Dash, et al., Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice. Nature Communications (2019). doi: 10.1038/s41467-019-10366-y
2. Image retrieved from: https://www.avert.org/about-hiv-aids/how-infects-body