Zinc Finger Proteins Put Personalized HIV Therapy Within Reach

– Researchers at the University of Pennsylvania School of Medicine and collaborators are using minute, naturally occurring proteins called zinc fingers to engineer T cells to one day treat AIDS in humans.

The first steps have been taken towards the goal of using modified T cells from an HIV-infected person for their own treatment. They showed that, using the zinc fingers, they could reduce the viral load of immune-deficient mice transplanted with engineered T cells.

Normally, zinc fingers bind to different bases in the DNA sequence to regulate the activity of genes. The zinc fingers used in this experiment were designed to bind to specific DNA sequences in the CCR5 gene. The CCR5 protein is one of the two cell-surface receptors needed for HIV to gain entry into a T cell in order to replicate.

In this study, the zinc finger protein brings a DNA enzyme to the CCR5 gene to cut a portion of its sequence, but due to the repair process a new mutation arises in the CCR5 protein, rendering it non-functional. Without a functional CCR5 protein on the cell’s surface, HIV cannot enter, presumably leading to resistance to HIV infection.

The researchers demonstrated this process in cell culture and in a mouse model. For the animal part of the study, the investigators used healthy human CD4 T cells and added DNA that expresses the zinc fingers, which modifies the CCR5 co-receptor. They grew the engineered cells in tissue culture flasks and transferred them into immune-deficient mice infected with HIV. “We followed them over time and showed that those mice that received the zinc-finger-treated cells showed less viral load than controls and improved CD4 counts,” says Perez.

The researchers are planning a clinical trial in humans in which T cells from HIV patients would have their CCR5 gene deliberately knocked out. These modified T cells could then be infused back into the patients to re-establish their immune system and decrease their viral load.

0 thoughts on “Zinc Finger Proteins Put Personalized HIV Therapy Within Reach”

  1. Human beings are absolutely unqualified to drive cars. I have never understood why people in traffic jams are all parked right up against each other’s bumpers. What was it about the slowing of traffic that made people decide to turn the road into a parking lot? You leave space between yourself and the next car even where traffic is stopped. Why is that so hard to understand? And if someone cuts into that space? Then good. They are bad drivers and you do not want them driving in the lane next to you anyway. Once the lane jumpers get ahead of you you will be surrounded by people who know how to drive. If even a small fraction of people on the road actually knew how to drive there would be far fewer traffic problems. The pulse and glide method demands paying attention to the amount of space in front of you so it would be helpful in this regard.

    I recently heard of another technique that a company used to reduce fuel use. It used computers to calculate the shortest routes for their trucks that also used the fewest left turns. It is one of those actions that has immediate benefits (the energy savings) and longer term benefits since not holding up traffic behind you helps reduce overall congestion.

    It will be interesting to see if more widespread use of traffic technology that uses current traffic conditions to give route advice will improve the overall flow of traffic.

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