HIV in cell culture can be completely eliminated!
New research from the Netherlands, presented ahead of the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024), unveils a promising breakthrough in the quest for an HIV cure. Led by Dr Elena Herrera-Carrillo and her team at Amsterdam UMC, the study demonstrates how cutting-edge CRISPR-Cas gene editing technology can effectively eradicate HIV from infected cells in laboratory settings.
CRISPR-Cas technology is a revolutionary tool in molecular biology, recognised with the Nobel Prize in Chemistry in 2020. It allows scientists to precisely modify the genetic code of living organisms by acting like molecular scissors,' guided by RNA molecules. This innovation enables targeted alterations to DNA, offering immense potential for advanced therapies. HIV presents a formidable challenge due to its ability to integrate into the host's DNA, making it resilient to conventional treatments. Despite the effectiveness of antiviral drugs, lifelong therapy is necessary as the virus can rebound from hidden reservoirs.
The researchers aim to develop a robust CRISPR-Cas regimen capable of targeting diverse HIV strains across various cellular environments, aiming for an inclusive 'HIV cure for all.' In their study, the researchers targeted conserved regions of the HIV genome, which remain constant across different strains. By focusing on these regions, they sought to create a broad-spectrum therapy capable of combating multiple variants effectively.
However, a logistical challenge arose due to the large size of the delivery vehicle (vector) required to transport the CRISPR-Cas components into cells. To address this, they experimented with techniques to downsize the vector, akin to fitting oversized luggage into a compact car for transport. Additionally, the researchers aimed to target HIV reservoir cells that remain dormant during antiretroviral treatment but can reignite the infection when treatment stops. They evaluated different CRISPR-Cas systems from various bacteria to assess their efficacy and safety in treating HIV-infected cells. Notably, one system, saCas9, demonstrated exceptional performance, effectively inactivating HIV with a single guide RNA and excising viral DNA with two guide RNAs. The strategy of minimising vector size improved delivery to HIV-infected cells, while targeting specific surface proteins on reservoir cells enabled precise localisation.
The authors stress that their work represents a proof of concept and caution against premature claims of an HIV cure. They emphasise the need to optimise delivery routes to target the majority of HIV reservoir cells while ensuring safety. Moving forward, they plan to combine CRISPR therapeutics with receptor-targeting agents and conduct preclinical studies to evaluate efficacy and safety comprehensively. Their goal is to achieve a balance between effectiveness and safety before considering clinical trials in humans.
In summary, the latest research offers hope for a potential HIV cure using CRISPR-Cas technology. By targeting conserved regions of the virus genome and optimising delivery methods, the study represents a significant step forward in the quest for an inclusive cure strategy.