University of Wisconsin-Madison researchers have developed a safer and more efficient way to deliver a promising new method for treating cancer and liver disorders and for vaccination — including a COVID-19 vaccine from Moderna Therapeutics that has advanced to clinical trials with humans.

The technology relies on inserting into cells pieces of carefully designed messenger RNA (mRNA), a strip of genetic material that human cells typically transcribe from a person’s DNA in order to make useful proteins and go about their business. Problems delivering mRNA safely and intact without running afoul of the immune system have held back mRNA-based therapy, but UW-Madison researchers are making tiny balls of minerals that appear to do the trick in mice.

“These microparticles have pores on their surface that are on the nanometer scale that allow them to pick up and carry molecules like proteins or messenger RNA,” says William Murphy, a UW-Madison professor of biomedical engineering and orthopedics. “They mimic something commonly seen in archaeology, when we find intact protein or DNA on a bone sample or an eggshell from thousands of years ago. The mineral components helped to stabilize those molecules for all that time.”

Murphy and UW-Madison collaborators used the mineral-coated microparticles (MCMs) — which are 5 to 10 micrometers in diameter, about the size of a human cell — in a series of experiments to deliver mRNA to cells surrounding wounds in diabetic mice. Wounds healed faster in MCM-treated mice, and cells in related experiments showed much more efficient pickup of the mRNA molecules than other delivery methods.

The researchers described their findings today in the journal Science Advances.

In a healthy cell, DNA is transcribed into mRNA, and mRNA serves as the instructions the cell’s machinery uses to make proteins. A strip of mRNA created in a lab can be substituted into the process to tell a cell to make something new. If that something is a certain kind of antigen, a molecule that alerts the immune system to the presence of a potentially harmful virus, the mRNA has done the job of a vaccine.

Image Credit:   University of Wisconsin