Researchers published a study in PNAS which found that a promising breakthrough in the elimination of human immunodeficiency virus type 1 (HIV-1) in humanized and infected mice was achieved by combining two CRISPR gene editing therapies with antiretroviral therapy (ART). This revolutionary treatment approach has the potential to transform the management of HIV-1 in humans.
The excision of HIV-1 DNA and the inactivation of CCR5 was brought together using gene-editing technologies built on observations from reported cures in human patients [with HIV],” said study author Kamel Khalili, PhD, Laura H. Carnell professor and chair of the Department of Microbiology, Immunology, and Inflammation and director at the Lewis Katz School of Medicine, in a press release. In the few instances of HIV cures in humans, the patients underwent bone marrow transplantation for leukemia, and the donor cells that were used carried inactivating CCR5 mutations.
The dual CRISPR technology developed in the study specifically targets two areas: the C-C chemokine receptor type 5 (CCR5) coreceptor of the HIV-1 virus, which enables the virus to enter cells, and the long terminal repeat (LTR)-Gag region of infected cells, where dormant viral DNA is present. By targeting both of these critical areas, the researchers were able to effectively eliminate the HIV-1 virus in humanized and infected mice, offering hope for a potential cure in the future.
Antiretroviral therapy (ART) is the current standard of care for HIV-1, but it only suppresses the virus, and does not completely eliminate it from the body. This means that individuals receiving ART are still at risk of developing acquired immunodeficiency syndrome (AIDS) and other complications associated with HIV-1. However, the study found that the dual CRISPR technology approach was able to completely eliminate the HIV-1 virus in some of the mice treated, providing evidence for the potential effectiveness of this innovative treatment approach in humans.
Overall, this study provides an important step forward in the development of a cure for HIV-1. By targeting the virus at its source and eliminating it completely, this revolutionary treatment approach may offer new hope for individuals living with HIV-1, and ultimately lead to the eradication of this deadly virus.
We demonstrate that further improvements in LASER ART and CRISPR for combinatorial editing of viral and strategically important cellular genes such as CCR5 in hu(manized) mice may achieve and serve as a proof-of-principle for further investigation toward clinical trials,” wrote study authors.