The research team was able to use their 2015 research where they used ultrasound waves to enhance drug delivery to the GI tract to figure out how to deliver much smaller nucleic acids, like RNA, to the colon.
Ultrasound is able to propel drugs and other molecules like RNA into cells through transient cavitation. Ultrasound makes tiny bubbles when made at low frequencies and those bubbles produce tiny jets when they burst that push drugs or RNA into cells.
Using this approach, researchers delivered short strands of RNA to the colon through an enema in a solution of water to block the inflammatory protein called tumor necrosis factor alpha (TNFα) in mice with colitis. They also used a small probe to deliver 0.5-second bursts of ultrasound that had frequencies of 20 to 100 kHz.
The study showed that mice that received the RNA using ultrasound experienced a seven to 10-time reduction in TNFα levels with their inflammations almost disappearing completely. The ultrasound and delivered RNA had no side effects on the mice.
“What we saw in this paper was the ultrasound can enable rapid delivery of these molecules,” said Carl Schoellhammer, a postdoc at MIT’s Koch Institute for Integrative Cancer Research and the study’s lead author. “In this case, it was proinflammatory molecules that we were shutting off, and we saw tremendous knockdown of those proteins.”
They also demonstrated that they could deliver messenger RNA (mRNA) that encodes protein-coding genes using the same approach. The researchers were able to deliver a firefly gene for bioluminescence. They hope to use this method to make cells produce proteins that could help patients with diseases caused by enzyme deficiencies.
According to the CDC, about 1.3 million people in the U.S. suffer from inflammatory bowel disease. While the cause is still unknown, MIT researchers hope that this technology will benefit inflammatory bowel disease patients first.
The researchers are working on a miniature device that could carry drugs and RNA in reservoirs that also have ultrasound waves into the stomach and GI tract.
“Eventually we think we will get to a fully ingestible capsule for the oral delivery of almost anything,” Schoellhammer says.
The National Institutes of Health, a Max Planck Research Award and a Koch Institute Quinquennial Cancer Research Fellowship funded the research.
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