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Friday, April 8, 2016
HIV RESISTS CRISPR GENE EDITING.
A recent study shows that the HIV virus can overcome new efforts to defeat it using gene-cutting CRISPR technology and that the act of editing the virus's genome could even introduce mutations that help it resist future attacks . The method to tackle HIV using CRISPR have been popular since the rise of the technique, but recent studies have found that HIV quickly continued replicating even after being treated with the gene-cutting enzyme and that mutations introduced by the cutting process rendered new HIV cells unrecognisable to the enzyme.
The research indicates that editing human genes to make HIV-resistant T cells would probably be more effective than directly editing the virus. Some researchers aim to edit genes made by the immune cells that HIV usually infects — called T helper cells — so that the virus cannot find a way in. Others take a different tack: equipping the T cells with gene-editing tools so that they can seek and destroy any HIV that infects them.
When HIV infects a T cell, its genome is inserted into the cell’s DNA and hijacks its DNA-replicating machinery to churn out more copies of the virus. But a T cell equipped with a DNA-shearing enzyme called Cas9, together with customized pieces of RNA that guide the enzyme to a particular sequence in the HIV genome, could find, cut and cripple the invader’s genome.
This seemed to work when a team led by virologist Chen Liang, at McGill University in Montreal, Canada, infected T cells that had been given the tools to incapacitate HIV. But two weeks later, Liang’s group saw that the T cells were pumping out copies of virus particles that had escaped the CRISPR attack. DNA sequencing revealed that the virus had developed mutations very near the sequence that CRISPR’s Cas9 enzyme had been programmed to cut.
The team think that the problem can be surmounted, for instance by inactivating several essential HIV genes at once, or by using CRISPR in combination with HIV-attacking drugs. Gene-editing therapies that make T cells resistant to HIV invasion (by altering human, not viral, genes) would also be harder for the virus to overcome. A clinical trial is under way to test this approach using another gene-editing tool, zinc-finger nucleases.
source;Nature news
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