New One-Time Gene Therapy a "Major Advance" in Treating HIV

Author:  Yangguang Ou
Institution:  Florida State University

After the results from a clinical trial, a group of researchers at the University of California, Los Angeles (UCLA) has just reported a promising gene therapy against the Human Immunodeficiency Virus. UCLA researcher Ronald T. Mitsuyasu, MD, and colleagues said that this was a "major advance in field of HIV gene therapy."

The Human Immunodeficiency Virus, commonly known as HIV, is a retrovirus, meaning it can transcribe its RNA sequence into DNA to be incorporated into the host's genome. HIV infection leads to Acquired Immunodeficiency Syndrome (AIDS), a condition marked by immune system failure and susceptibility to many diseases. The Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) have reported that approximately 25 million people have died from AIDS since it was first recognized in December of 1981. HIV targets cells in the immune system such as helper T cells (especially CD4 T cells), macrophages, and dendritic cells. When the concentration of these cells falls below a certain level, the infected individual develops AIDS.

The clinical trial, the largest test ever to examine genetically altered human cells, was a 100-week study of 74 HIV-infected patients. The treatment involved injection of a growth factor that induced accelerated production of white blood cells in the body. After injection, the cells were isolated from the patients' blood samples and cultured to test. The stem cells from these cultures were then infected with a genetically-engineered mouse virus called OZ1 in order to incorporate anti-HIV genes into the stem cell genome. These anti-HIV genes, according to the paper published in the online issue of Nature Medicine on February 16, 2009, code for an enzyme called ribozyme that "specifically targets and inactivates HIV genes." These stem cells were then injected back into the patients, where they returned to the bone marrow to produce more anti-HIV T-cells (a type of white blood cell).

Of the 74 patients, 38 were treated with new therapy while the rest were given placebo. According to the study, all patients had HIV infections and kept their infections under control with anti-retroviral drug combinations. The results showed that, first and foremost, there were no side effects of the treatment throughout the study period. It also showed that, during the study period of almost two years, the HIV virus did not develop resistance to the anti-HIV ribozymes, which deviates from expectations since microorganisms most often do develop some kind of resistance due to constant genetic mutation.

Additionally, during the study, the patients with treatment had a higher CD4 T-cell (which the HIV attacks and destroys) count than those with placebo. The patients with the OZ1 infusions also had a lower HIV viral load and a longer gap time before restarting treatment. "This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product," wrote the authors of the study.

Due to the positive results of the study, researchers are planning to increase the dosage of the gene infusions, improve transfer of the injected anti-HIV stem cells back into the bone marrow, and recombinantly attach even more potent anti-HIV genes. In the future, the researchers are planning to start the gene therapy before any other medicinal treatments.

Written by: Yangguang Ou

Edited by: Brittany Raffa and Renee Gilberti

Published by: Hoi See Tsao