Antiretroviral drugs have turned HIV/AIDS from a fatal disease into one that can often be controlled, but they are not a cure. That’s why the CIRM Board approved $6.85 million for a therapy designed to cure the disease. This is CIRM’s 82nd funded clinical trial.
Millions impacted
About 38 million people worldwide live with HIV/AIDS, and 1.5 million new cases occur each year. Most people do not have access to lifesaving antiretroviral medications. Those who do often face long‑term complications, including heart, bone, liver, and kidney problems, and metabolic changes.
ART reduces viral load but cannot eliminate HIV because the virus integrates into long‑lived cells and becomes dormant. When treatment stops, the virus can reactivate.
Dr. William Kennedy and the team at Excision Bio Therapeutics developed EBT‑101, the first clinical study using a CRISPR‑based platform to cut out latent HIV‑1, the most common form in the U.S. and Europe. The goal is to eliminate or sharply reduce the virus’s hidden reservoirs so patients can be effectively cured.
“To date, only a handful of people have been cured of HIV/AIDS, so using gene editing to eliminate the virus could be transformative,” says Dr. Maria Millan, CIRM President and CEO. “In California alone, nearly 140,000 people live with HIV. It continues to disproportionately affect marginalized communities, many of whom cannot access the medications that control the virus. A functional cure would have enormous impact here and worldwide.”
Landmark moment
In a news release announcing they had dosed the first patient, Daniel Dornbusch, CEO of Excision, called it a landmark moment. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first-ever clinical assessment of a multiplexed, in vivo gene editing approach. We reached this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease.”
The Excision Bio Therapeutics team also scored highly on its Diversity, Equity, and Inclusion plan. Reviewers praised them for adding a partner organization committed to serving underserved populations and for engaging a community advisory board to help guide patient recruitment.
CIRM has already invested almost $81 million in 20 projects targeting HIV/AIDS, including four clinical trials.
The aim of clinical treatment is lethally killed the HIV, instead of producing biological functioning proteins. It is not necessarily to take account the existence of introns and exons in genome of viruses. Therefore, CRISPR -CAS9 can be considered effective tool to cut genome HIV into pieces and further prevent formation of active virus.
The approach of EBT-101 by using Adeno-adsociated virus (AAV) as a vector to transfer CRISPR-CAS9 for invivo gene editing treatment may end up with disappointing results. The potential of AAV is limited for incapability to accomplish targeted, cell-specific gene delivery and expression of therapeutic genes in nontargeted subsets. This is evidence by CF gene therapy in human which showed recombinant AAV is less efficiently tranfected primary cells and that the presence of helper virus is required for recombinant AAV gene expression raises questions about the efficiency of gene transfer in vivo with purified AAV.
As HIV infection significantly destroy CD4+T helper cells resulting in CD4+ T cells number below the critical levels and loss of cell-mediated immunity. It is highly recommended that CRISPR approach complexed to the polymeric immunoglobulin CD4 receptor may improve specificity and efficiency of treatment.
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