The first clinical trial of a gene-editing therapy for human immunodeficiency virus type 1 (HIV) infection is now underway, thanks to a major collaborative effort between scientists at the Lewis Katz School of Medicine at Temple University and investigators at Excision BioTherapeutics, Inc. The trial, designed to evaluate the safety, tolerability, and efficacy of EBT-101, a unique gene-editing treatment that could alter the future of HIV therapeutics, marks a major step forward in the effort to find a cure for HIV/AIDS.

“This is an unprecedented and exciting time for all, particularly for those who have been searching for solutions to the HIV/AIDS pandemic over the last 40 years, including scientists and health care providers,” said Kamel Khalili, PhD, Laura H. Carnell Professor and Chair of the Department of Microbiology, Immunology, and Inflammation, Director of the Center for Neurovirology and Gene Editing, and Director of the Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine. Dr. Khalili is also a cofounder of Excision BioTherapeutics. The trial will take place at multiple locations, but Temple is not one of the sites.

Dr. Khalili and colleagues at Temple have led the way in the development of EBT-101, which is based on the popular gene-editing technology known as CRISPR and is tailored specifically for excising the genetic material of HIV from infected cells. The unique ability of EBT-101 to remove HIV proviral DNA from cells was demonstrated at Temple in experiments in HIV-infected human cells and in cells of humanized mice.

Tricia H. Burdo, PhD, Associate Professor in the Department of Microbiology, Immunology, and Inflammation at the Katz School of Medicine, took the research a step further, carrying out studies in non-human primates. Her findings, which demonstrated the effectiveness of the CRISPR-based technology, played a critical role in advancing EBT-101 into clinical studies.“Our research here at Temple created the foundation in part needed for Excision to initiate the clinical trial,” Dr. Burdo said. “It is exciting to now see the research moving forward in humans.” Dr. Burdo serves on the Scientific Advisory Board for Excision BioTherapeutics.

“We have an outstanding team at Temple University, who made several key discoveries and were instrumental in leading preclinical studies using CRISPR gene therapy for elimination of HIV proviral DNA,” Drs. Khalili and Burdo said in a joint statement. “We are ecstatic to see Excision BioTherapeutics obtain FDA approval to start a first-in-human Phase I/II clinical trial using the technology developed here at Temple.”

“The launch of clinical trials for EBT-101 is a pivotal milestone for Drs. Khalili and Burdo, their teams, and Temple University,” said Amy J. Goldberg, MD, FACS, Interim Dean of the Lewis Katz School of Medicine. “Their remarkable scientific knowledge and passion for innovation have led to a therapy with life-saving, life-extending potential. I am so proud they are a part of our Temple family.” 

In participants enrolled in the clinical trial, EBT-101 will be administered as a single intravenous infusion. The strategy will allow investigators to explore the possibility of using EBT-101 as a one-time curative therapy for individuals with HIV. The curative aspect of the gene-editing therapy lies in its ability to remove viral DNA from the genomes of cells and tissues that serve as HIV reservoirs. Such reservoirs, which allow the virus to hide from existing antiretroviral therapies, have long hindered the development of an HIV cure.

For more information, see ClinicalTrials.gov identifiers NCT05144386 (Phase 1/2 trial) and NCT05143307 (long-term follow up trial).

Editor’s Note: Kamel Khalili is Co-Founder and Chief Scientific Consultant and holds equity in Excision BioTherapeutics, which has licensed the viral gene-editing technology from Temple University. Kamel Khalili is a named inventor on patents that cover the viral gene-editing technology. Tricia Burdo holds equity in Excision BioTherapeutics. These named researchers are employed by Temple University and conduct research activities sponsored by the company. Questions regarding their affiliations with Temple University may be directed to [click-for-email].

In addition to owning the viral gene-editing technology that Excision is licensing, Temple University also holds an equity interest in Excision. As a result of these interests, Temple University could ultimately potentially benefit financially from the outcome of this research. These interests have been reviewed and approved by Temple University in accordance with its Institutional Conflict of Interest policy. Questions about this can be directed to [click-for-email].