One-time gene therapy injection could provide HIV treatment that could last a lifetime
Jonah Sacha, Ph.D., at OHSU’s Oregon National Primate Research Center and the Vaccine and Gene Therapy Institute. (OHSU/Christina Wentz-Graf)
A new pre-clinical study in nonhuman primates will evaluate the potential use of an experimental drug as gene therapy that could prevent people with HIV from taking daily antiviral drugs for the rest of their lives.
The research will be led by researchers from Oregon Health and Science University Jonah Sacha, Ph.D., Joe also serves as a scientific advisor to CytoDyn, a biotechnology company that develops the drug called leronalimab. The study is funded by a five-year grant of up to $5 million that was recently awarded to OHSU by the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health.
“This grant will fund the development and early studies of leronalimab as a potential single-injection gene therapy,” said Professor Sacha, from OHSU’s Vaccine and Gene Therapy Institute and the Oregon National Primate Research Center. “If this approach works as hoped, it could provide a functional cure for HIV, meaning it could suppress HIV enough that patients no longer need to take daily antiviral pills for the rest of their lives.” will not be needed.”
In an earlier study, Sacha and colleagues found that leronalimab completely prevented nonhuman primates from becoming infected with the monkey form of HIV. That result indicated that leronalimab showed promise as a potential pre-exposure drug for preventing human infection with the virus that causes AIDS.
Now, this study aims to devise a way to introduce leronalimab as a gene therapy. Sacha and colleagues will explore how to place the coding sequence of the experimental drug inside a laboratory-made form of an adeno-associated virus, an approach that gene therapy researchers call an AAV vector. The resulting therapy will then be injected inside the body where muscle cells will make the leronalimab last longer.
Laronlimab is a monoclonal antibody that blocks HIV from entering immune cells through a surface protein called CCR5. The drug has demonstrated that it can mimic a CCR5-deficient donor by capturing all available CCR5 molecules, but this will require a new method for delivery as a gene therapy. Viral vectors have been used for decades to deliver antigens from specific pathogens.
In this project, researchers will design a synthetic AAV vector to enable long-term production of leronalimab inside the body. The goal is to develop a safe and effective single injection that suppresses HIV replication and eliminates the need for life-long antiretroviral therapy.
“Currently, patients often take multiple antiretroviral pills daily,” Sacha said. “Removing the burden of this pill could not only improve patients’ quality of life, but could also address problems with adherence.”
Rhesus macaques at OHSU’s Oregon National Primate Research Center that have been exposed to a monkey version of HIV will be given a single AAV injection that contains leronalimab. Researchers will monitor nonhuman primates for years to assess the safety and efficacy of this approach.
This research is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI166969. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
To ensure the integrity of our research and as part of our commitment to public transparency, OHSU actively controls, tracks and manages the relationships that our researchers may have with entities outside of OHSU. In connection with this research, Dr. Sacha has a significant financial interest in CytoDyn, a company that may have a commercial interest in the results of this research and technology. review OHSU conflicts of interest program details To learn more about how we manage these business relationships.
All research involving animal subjects at OHSU must be reviewed and approved by the university’s Institutional Animal Care and Use Committee (IACUC). The priority of the IACUC is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of people working with animals. No live animal work may be performed at OHSU without IACUC approval.
