Researchers at Arrowhead Madison have created siRNA targeting and delivery methods that could be more than 500 times more effective than existing technologies. Small interfering RNAs have shown great promise in silencing genes, but scientists have struggled to deliver these potential drugs.
The issues with siRNA delivery include that the immune system sees the systemically delivered fragments of genetic material as foreign and destroys them. If they get past the immune cells, they have to be targeted to the cells of interest and get inside them without being destroyed by the cells' internal pathways.
When siRNA is linked to cholesterol, it targets the liver and silences genes in animal models, but it has to be delivered at high doses because it becomes trapped in endosomes (small membrane-bound spheres) in the liver cells, stopping it from interacting with the DNA. Arrowhead's researchers in Madison, WI, added a polymer that targets liver cells and breaks open the endosomes. This increased the efficacy of the siRNA more than 500 times and reduced the expression of the gene in both mice and nonhuman primates.
Arrowhead Madison, formerly Roche Madison, got its current name in October 2011 when Arrowhead Research ($ARWR) snapped up Roche's ($RHHBY) RNA-interference assets, including technology, staff and labs, when the big pharma company decided to step away from this complex and sometimes troubled field.
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