London, July 1 : Researchers have taken a step forward to bringing personalized HIV therapy within reach by using tiny, naturally occurring proteins called zinc fingers to engineer T cells.
In the study conducted using a mouse model, researchers from University of Pennsylvania School of Medicine found that with the help of zinc fingers they could reduce the viral load of immune-deficient mice injected with engineered T cells.
"By inducing mutations in the CCR5 gene using zinc finger proteins, we've reduced the expression of CCR5 surface proteins on T cells, which is necessary for the AIDS virus to enter these immune system cells," Nature quoted first author Elena Perez, Assistant Professor of Pediatrics at Penn, as saying.
"This approach stops the AIDS virus from entering the T cells because it now has an introduced error into the CCR5 gene," she added.
Those individuals born with mutations on CCR5 gene are immune to HIV infection and apparently not influenced by the non-functional CCR5 protein.
Usually, zinc fingers are hooked to different bases in the DNA sequence to control gene activity.
During the study, zinc fingers were crafted to hook on to specific DNA sequences in the CCR5 gene.
This protein is one of the two cell-surface receptors that push HIV to enter into a T cell in order to replicate.
They found that 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, making it non-functional.
Without a functional CCR5 protein on the cell's surface, HIV cannot enter, apparently developing resistance to HIV infection.
In 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," said Perez.
The researchers are now planning to conduct human trials for using modified T cells from an HIV-infected person for their own treatment.
The study appears in advanced online issue of Nature Biotechnology.