Stanford Scientists Use Copy/Paste Method to Make Cells HIV Resistant
January 24, 2013 8:59 AM
The method stopped HIV from entering healthy immune cells
Stanford scientists have found a way to protect the immune system from HIV by
placing resistant genes into T cells
Researchers from the Stanford University School of Medicine, led by Matthew Porteus, MD, have used a cut and paste method where HIV-resistant genes were coupled with T cells to deny the virus' entry into healthy immune cells.
The HIV virus typically enters immune cells by binding to one of two surface proteins: CCR5 and CXCR4. However, some people have a mutation in CCR5 that makes them resistant to HIV.
Porteus and his team used this idea to create a method for making this protein inactive. They used a protein, called a zinc finger nuclease, that finds and attaches to the CCR5 receptor gene and modifies it to imitate the mutated, inactive versions. It does this by breaking up pieces of DNA.
In addition to breaking a sequence in the CCR5 receptor's DNA, the team pasted three genes that are resistant to HIV. They help protect the cells via both the CCR5 and CXCR4 receptors. This technique is called stacking, where multiple layers of protection are used to protect the cells.
In tests, T cells with single, double and triple gene modifications were protected against HIV. However, as expected, the triplets were much more resistant to infection. In fact, they had 1,200-fold
protection against HIV
carrying the CCR5 receptor and 1,700-fold protection against those carrying the CXCR4 receptor.
T cells without any protection were infected within 25 days.
"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," said Porteus. "We can use this strategy to make cells that are resistant to both major types of HIV."
There are two issues that the team has to work out, though. First, the zinc finger nuclease could cause a break elsewhere in the DNA and cause cancer. Second, the cells may not accept the genetic change.
Stanford School of Medicine
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