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Gene Therapy Targets Aids

by | Jun 6, 2023 | Biotech for Non-Scientist

For many years, a diagnosis of acquired immunodeficiency syndrome (AIDS) was a death sentence. It seemed unthinkable in the 1980s, but the medical community now primarily treats the disease as a chronic illness. This profound shift arose from the development of highly active antiretroviral therapies (HAART). These medicines inhibit the replication and spread of the human immunodeficiency virus (HIV), which causes AIDS. They provide hope and new life to millions.

However, HAART has significant side effects, such as fatigue, nausea, vomiting, diarrhea, fever, muscle pain, kidney and liver damage, heart disease, and insulin resistance. More significantly still, the treatment can never be completely effective. That’s because HIV evades the therapy in two challenging ways:

  • High mutation rate: The HIV genome evolves rapidly. Its endless transformation changes the viral proteins HAART works on, rendering the therapies ineffective. Nonetheless, patients try to stay ahead of the virus with daily medication. In turn, pharmaceutical companies are continually working to develop new HIV drugs.
  • Latency: People with HIV typically have a reservoir of immune cells that contain inactive or latent HIV. The virus is essentially dormant in this state and can remain so for years. However, latent microbes can reawaken at any time and start making more HIV.

Because HAART targets only active viruses, latency enables HIV to “hide.” Many in the field of HIV research consider tackling this viral reservoir the final frontier in successfully fighting the virus. In this article, we focus on technology developed by American Gene Technologies (AGT; Rockville, MD) to address chronic HIV infection.


Scientists originally conceived gene therapy to treat disorders caused by a single genetic mutation, such as sickle cell disease, cystic fibrosis, or spinal muscular atrophy. This therapy can address other illnesses, such as cancer and HIV. AGT uses gene therapy to eradicate latent HIV and eventually offer a cure.


How does HIV infect immune cells, to begin with? HIV first destroys the immune system’s helper T-cells. These are specialized white blood cells that recognize a unique target, usually a specific protein on the surface of a pathogen. Once they lock on, the helper T’s release inflammatory cytokines—chemical messengers that help rev up the immune system. This includes activating cytotoxic or “killer” T-cells, which directly destroy invading microbes.

Without the helper T-cells, the immune system breaks down. That’s how HIV kills—by disabling the very cells that fight it. In fact, although HIV infects all types of helper T-cells, it appears to infect helper T-cells that are specific to HIV preferentially. After first wiping out those helper T’s, the virus can disable the rest.


AGT’s experimental treatment, AGT103-T, is designed to shore up those vulnerable helper T-cells by disabling latent HIV and preventing new infections. The new approach is a type of autologous cell therapy. That means doctors engineer a patient’s cells to use as medicine using the following steps:

  • Isolate HIV-specific helper T-cells from patient blood;
  • Use gene therapy viral vector to deliver AGT103 to the isolated cells;
  • Expand the treated cell population in the lab and infuse it back into the patient

The modified HIV-specific helper T-cells can now disable any latent virus that reawakens while simultaneously resisting new infection. That means they can effectively fight any existing HIV-infected helper T-cells. The ultimate goal of the therapy is to enable HIV patients to effectively fight HIV infection while eliminating or reducing the need for HAART and its unwanted side effects.

How does AGT103 make helper T-cells resistant to HIV? It is a type of gene therapy; instead of delivering a gene that provides the recipe for a protein, it delivers genes that code for “antisense” RNAs—RNAs that disrupt the production of other proteins. The three proteins whose production is disrupted are:

  • CCR5, a protein on the surface of helper T-cells. HIV needs protein in order to get inside them. Without CCR5, the cells will be resistant to infection.
  • VIF, or “viral infectivity factor,” an HIV protein. If a helper T-cell is already infected with HIV, knocking out vif makes it impossible for the virus to replicate itself.
  • Tat, or “transactivator of transcription,” another HIV protein required for the virus to make new proteins. No tat means no new viral proteins and no new virus.

AGT103-T is currently in Phase 1 clinical trials.


The viral vector used by AGT derives from HIV itself. Called lentiviral vectors, they’re also used to create CAR-T therapies.

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Author: Emily Burke, PhD
Editor: Sarah Van Tiems, MS
Scientific Review: Tahir Hayat, MS


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