Scientists have created a technique to genetically engineer HIV-resistant cells, a method which if proven effective in humans, could give HIV positive patients an alternative to a lifelong medication schedule which current patients now face.
HIV is dangerous because of the virus’ capability to break into and eliminate T-cells, gradually developing into AIDS causing the breakdown of the immune system. The virus is able to breach the T-cells by two genes – CXR4 and CCR5 – that are notoriously receptive to the virus.
The medications prescribed to combat HIV are aimed at both of those receptor genes. However, if the genes could be modified in a way that makes them naturally immune to HIV, the daily medication schedule would no longer be necessary.
A new study conducted by researchers from the Stanford University School of Medicine describes the use of “molecular scissors” to cut and paste several HIV-resistant genes into T cells. The findings were published in the journal Molecular Therapy.
Matthew Porteus, MD, an associate professor of pediatrics at Stanford and a pediatric hematologist/oncologist at Lucile Packard Children’s Hospital, and chief investigator said:
“We inactivated one of the receptors that HIV uses to gain entry and added new genes to protect against HIV, so we have multiple layers of protection, what we call stacking. We can use this strategy to make cells that are resistant to both major types of HIV.”
A tailored gene therapy, this new method could eventually replace drug treatment all together. The study was done in the laboratory; clinical trials still need to measure whether the new approach would function as therapy.
Sara Sawyer, PhD, assistant professor of molecular genetics and microbiology at the University of Texas-Austin and a co-author of the study said:
“Providing an infected person with resistant T cells would not cure their viral infection. However, it would provide them with a protected set of T cells that would ward off the immune collapse that typically gives rise to AIDS.”
AIDS is a challenging virus to treat because it is constantly mutating, leaving patients to be treated by a list of different drugs – or active antiretroviral therapy (HAART). The current study avoided this problem via a multi-pronged genetic attack that deflects HIV on several fronts. The researchers aimed to mimic HAART through genetic manipulation.
The Stanford scientists used the nuclease to pinpoint an undamaged section of the CCR5 receptor gene’s DNA. They formed a break in the sequence, and in an achievement accredited to genetic editing, pasted in three genes known to have resistance to HIV. Placing several genes at a specific site is known as “stacking”.
Combining the three immune genes helped guard the cells from HIV through both the CXCR4 and CCR5 receptors. Many layers of security were put in place by disabling the CCR5 gene as well as the addition of the anti-HIV genes.
Researchers then tested the T cells’ protective abilities by creating versions in which they placed one, two, and all three of the genes and exposed the T cells to HIV.
The triple modified genes were by far the most immune to infection. The T cells that hadn’t been modified ended up giving into infection within 25 days.
The authors are encouraged by this study’s results as a stepping stone in gene therapy development for HIV. One drawback associated with this method could be that the nuclease is designed to make a break in just one spot – could make a break elsewhere, causing cancer or other cell deviations. It is also possible that the cells may not endure the genetic change.
Porteus said, “It’s possible the cells won’t like the proteins they’re asked to express, so they won’t grow.”
However, he suggests that both of these problems are able to be technically overcome. The next step will be to test the method in T cells taken from AIDS patients and move towards animal testing. Authors hope that clinical testing will begin within three to five years.
Despite the new technique being labor-intensive and needing a custom approach for each patient, the HIV positive patients could potentially be saved from a grueling, expensive, lifelong dependence on drug treatments.
Just a few days ago, it was reported that the U.S. healthcare system could be saving over $1 billion by prescribing generic medications for antiretroviral therapy. However, this approach runs the risk of poorer quality and effectiveness of HIV treatment.
Written by Kelly Fitzgerald