The use of antiretroviral drugs has turned HIV/AIDS from a fatal disease to one that can, in many cases in the US, be controlled. But these drugs are not a cure. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to approve investing $6.85 million in a therapy that aims to cure the disease.
This is the 82nd clinical trial funded by CIRM.
There are approximately 38 million people worldwide living with HIV/AIDS. And each year there are an estimated 1.5 million new cases. The vast majority of those living with HIV do not have access to the life-saving antiretroviral medications that can keep the virus under control. People who do have access to the medications face long-term complications from them including heart disease, bone, liver and kidney problems, and changes in metabolism.
The antiretroviral medications are effective at reducing the viral load in people with HIV, but they don’t eliminate it. That’s because the virus that causes AIDS can integrate its DNA into long-living cells in the body and remain dormant. When people stop taking their medications the virus is able to rekindle and spread throughout the body.
Dr. William Kennedy and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. This is the first clinical study using the CRISPR-based platform for genome editing and excision of the latent form of HIV-1, the most common form of the virus that causes AIDS in the US and Europe. The goal is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured.
“To date only a handful of people have been cured of HIV/AIDS, so this proposal of using gene editing to eliminate the virus could be transformative,” says Dr. Maria Millan, President and CEO of CIRM. “In California alone there are almost 140,000 people living with HIV. HIV infection continues to disproportionately impact marginalized populations, many of whom are unable to access the medications that keep the virus under control. A functional cure for HIV would have an enormous impact on these communities, and others around the world.”
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 were able to reach 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 high on their plan for Diversity, Equity and Inclusion. Reviewers praised them for adding on a partnering organization to provide commitments to serve underserved populations, and to engaging a community advisory board to help guide their patient recruitment.
CIRM has already invested almost $81 million in 20 projects targeting HIV/AIDS, including four clinical trials.
The Stem Cellar 
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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