Researchers have successfully designed and tested a gene therapy delivery method for making CD4 cells resistant to HIV infection that is much simpler to administer than most other methods currently being studied, according to a study published online September 1 in the Journal of Acquired Immune Deficiency Syndromes.

The gene therapy field is still in its infancy, but it holds promise for diseases such as HIV currently requiring lifelong treatment that is both costly and potentially toxic. Most experimental gene therapy methods, however, are complicated—and therefore expensive—and not without risks.

Current gene therapy strategies involve removing and sorting stem cells from the blood or bone marrow, genetically altering those cells to produce HIV-resistant CD4s, and then infusing them back into a person. There is also usually the need to destroy CD4 cells in the body that are already infected with HIV or still at risk of becoming infected, to allow the altered cells to thrive—a highly toxic component of gene therapy treatment.  

Joseph Anderson, PhD, and his colleagues from the University of California in Davis are taking a different approach. They hope to develop a way to deliver new genes to target cells that won’t require altering human cells outside the body, nor the complications involved with it.

Anderson’s team started at the same place as a number of other gene therapy products currently in development. All aim to get the body’s immune cells to stop producing a surface receptor called CCR5, which the virus needs to infect those cells. If a person’s cells stop producing CCR5, this could either give them significant protection from HIV infection in the first place or slow down the disease process if they are already infected or become infected.

Anderson’s group has developed a hybrid gene delivery device that doesn’t require taking cells out of the body. Instead, they have taken a naturally occurring genetic splicing molecule, called interfering RNA, packaged it inside a hollowed-out Sindbis virus and attached a monoclonal antibody to the surface so that these viral delivery devices (called a vector) interact only with the immune cells the team wants them to genetically alter.

Thus far, the team members have conducted two successful sets of experiments. In the first, they proved that their gene therapy can deliver the genetic payload to CD4 cells and cause them to stop making CCR5. They then tried injecting the gene therapy into specially bred mice that have human immune cells. Two weeks after the injections, the human immune cells in the mice no longer had CCR5 receptors, and the cells were highly resistant to HIV infection.

The authors acknowledge that they have a long road ahead of them, but they are actively conducting additional experiments to further develop their gene therapy. They conclude that the field has great promise for both treatment and prevention of HIV.