Thousands fold better gene expression with RNA switch

Thousands fold better gene expression with RNA switch

If scientists could precisely regulate gene expression, they could turn off the genes responsible for illness and disease and turn on those that enhance health and the immune system.

The team has developed a powerful and versatile tool that achieves gene activation thousands of times better than nature.

"All we did was make an RNA switch that turns a gene on," said the senior author. "But what really makes it awesome is that it's really, really, really good."

Using a computational design approach, they created the switch by molecularly programming an RNA molecule called Small Transcription Activating RNA, or STAR that the group had previously discovered. They then use an algorithm to optimize the STAR for specific applications. An outside company uses the algorithm's results to construct a physical piece of RNA, which the researchers then use in experiments. The research is published in the journal Nature Communications.

Senior author likens STARs to a light switch. Continuing the analogy, the RNA switches found in nature are unable to turn the "lights" fully on or off. Often times the room is consistently dim instead of completely dark or brilliantly light. But researchers have desired to have a tighter control of the system. The STAR can turn on the light -- or activate a gene -- 9,000 times brighter than without the STAR present, providing the completely dark or light room that researchers have lacked.

"If you study a system to explore what a gene does, you want to know what it does when it's completely on or off," senior author explains. "Not when the gene is there or halfway there. That's much harder to disentangle."

That's particularly true for diagnostic applications, which the senior author plans to pursue next with the new tool. Because RNA excels at detecting other strands of RNA, STARs could be useful in diagnosing RNA viruses. To do this, the switch could be engineered to turn on in the presence of one of these viruses.