First CRISPR Gene Editing Treatment For HIV Data Released

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First CRISPR Gene Editing Treatment For HIV Data Released

First CRISPR Gene Editing Treatment For HIV Data Released

On October 25, 2023, Excision BioTherapeutics presented positive mid-term data from the phase 1/2 clinical trial of EBT-101, a CRISPR-Cas9 gene editing-based treatment for HIV, at the 30th European Society of Gene and Cell Therapy (ESGCT) Annual Congress.

EBT-101 represents the world’s first human clinical trial for treating HIV using CRISPR gene editing technology and received FDA approval for human clinical trials at the end of 2021.

First CRISPR Gene Editing Treatment For HIV Data Released

The company stated that establishing the safety and biodistribution of EBT-101 is a critical initial step in the clinical program. Among the first three trial participants, treatment with EBT-101 did not result in severe adverse events or dose-limiting toxicities; all reported adverse events were mild and reversible. Furthermore, positive biodistribution of EBT-101 was detected in the blood of all participants. These initial observations provide vital clinical data supporting the progression of the trial to the next dose level (increasing from 9.0×1011 vg/kg to 3.0×1012 vg/kg).

Excision CEO Daniel Dornbusch emphasized their commitment to developing curative therapies based on CRISPR for infectious diseases. EBT-101, a CRISPR-based gene therapy, is being tested as a potential functional cure for HIV. Sharing this preliminary safety and biodistribution data is considered important for the HIV community and other gene therapies in development.

AIDS, or Acquired Immunodeficiency Syndrome, is a highly infectious disease caused by the Human Immunodeficiency Virus (HIV). HIV can attack and severely compromise the human immune system, making AIDS patients susceptible to secondary infections and cancers, resulting in a high mortality rate.

According to data from the United Nations Programme on HIV/AIDS, the number of HIV carriers and AIDS patients worldwide increased from 34.3 million at the end of 2013 to 38 million at the end of 2018, with numbers continuing to rise rapidly.

While antiretroviral therapy (ART) has greatly extended the lifespan and prognosis of AIDS patients, it brings about serious side effects and the development of drug resistance.

Moreover, HIV, as a retrovirus, can integrate its genome into the host cell’s chromosomes, meaning current antiretroviral therapies can only suppress the virus and not eliminate it entirely, thus failing to cure AIDS.

Excision stated that the current standard treatment for AIDS involves antiretroviral therapy, which prevents the replication of the HIV virus within the body but cannot clear the virus completely. Patients must undergo prolonged treatment with significant side effects affecting their quality of life. CRISPR-based gene editing therapies hold the promise of replacing current antiretroviral therapy to achieve a “complete cure” for AIDS.

In November 2020, researchers from Temple University and the University of Nebraska Medical Center published a study in Nature Communications, demonstrating successful gene editing and elimination of the SIV virus closely related to HIV in non-human primates, marking a significant step in AIDS research. This breakthrough brought humanity closer to developing a comprehensive cure for AIDS.

First CRISPR Gene Editing Treatment For HIV Data Released

This breakthrough signifies that a new approach with the potential to end the AIDS nightmare has been found. Excision has obtained authorization from Temple University to conduct clinical research and development.

CRISPR-Cas9 gene editing is well-known for its precision in cutting double-stranded DNA, leading to DNA breaks. Based on this principle, CRISPR-Cas9 can be used to cut the HIV genome integrated into human chromosomes.

However, if only one site is cut, it can be easily repaired and may lead to genetic mutations near the cut site. This therapy involves multiple cuts to completely fragment the HIV genome, thereby achieving complete clearance of the virus.

First CRISPR Gene Editing Treatment For HIV Data Released

Prior testing in non-human primates showed that the CRISPR-Cas9 system delivered by an adeno-associated virus (AAV9) vector could reach tissues where the virus is present, including bone marrow, lymph nodes, and spleen, especially in CD4+ T cells, which are essential host cells for the HIV virus, thus clearing the virus.

In addition to CRISPR-based HIV therapy, the company’s research pipeline also includes using CRISPR technology to clear the Hepatitis B virus (HBV), Herpes Simplex Virus (HSV), and JC polyomavirus (JCV).