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Researchers temporarily turn off essential gene using RNAi technology

April 19, 2016

The shRNAs that targeted RPA3 were linked to a fluorescent tag. These were then used to generate transgenic mice in such a way that the team could trigger RNAi and shut off the RPA3 gene when the animals were fed a drug like tetracycline but not when the drug was withdrawn. The fluorescent tag allowed the scientists to easily monitor the tissues in which the target RPA3 gene had been switched off.

When the scientists induced RPA3 suppression in adult mice, the animals' intestinal tissues rapidly atrophied and the mice lost weight and died within 8-11 days. But if the researchers withdrew the drug when the mice were almost at the point of death, both atrophy and weight loss were fully reversed and the mice survived. While the authors plan to further study these mice to understand mechanisms of tissue maintenance and regeneration, they are also excited by the broader implications of their new approach.

"This ability to toggle gene activity at any stage is a major advance over other gene knockdown techniques that are not reversible," says Stillman. "This approach in animal models is the closest genetic equivalent to treating human patients with a single dose of a small molecule-based therapy targeted at a particular gene. So this system will be invaluable for testing novel therapeutic targets and evaluating their efficacy and side-effects."

Source: Cold Spring Harbor Laboratory