A new study to be presented at the European Congress of Clinical Microbiology and Infectious Diseases later this month has shown how CRISPR-Cas gene editing technology can be used to eliminate all traces of the HIV virus from infected cells in the laboratory, raising hopes of a cure.
One of the significant challenges in HIV treatment is the virus's ability to integrate its genome into the host's DNA, making it extremely difficult to eliminate. The researchers, from Amsterdam UMC, Netherlands, explain that the CRISPR-Cas genome editing tool provides a new means to target HIV DNA, with the aim of developing a robust and safe combinatorial CRISPR-Cas regimen that can inactivate diverse HIV strains across various cellular contexts.
In this research, the team used CRISPR-Cas and two gRNAs against conserved HIV sequences, focusing on parts of the virus genome that stay the same across all known HIV strains, and achieved cure of HIV-infected T cells. The strategy of minimizing the vector size was successful, enhancing its delivery to HIV-infected cells. The researchers were also able to target hidden HIV reservoir cells by focusing on specific proteins found on the surfaces of these cells.
The authors emphasize that their work represents proof of concept and will not become a cure for HIV tomorrow. “Our next steps involve optimizing the delivery route to target the majority of the HIV reservoir cells. We will combine the CRISPR therapeutics and receptor-targeting reagents and move to preclinical models to study in detail the efficacy and safety aspects of a combined cure strategy. This will be instrumental to achieve preferential CRISPR-Cas delivery to the reservoir cells and avoiding delivery into non-reservoir cells. This strategy is to make this system as safe as possible for future clinical applications. We hope to achieve the right balance between efficacy and safety of this CURE strategy. Only then can we consider clinical trials of ‘cure’ in humans to disable the HIV reservoir. While these preliminary findings are very encouraging, it is premature to declare that there is a functional HIV cure on the horizon.”