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A breakthrough in our understanding of mRNA delivery systems in the body may allow for more direct treatments for pancreas-related diseases, including cancer and diabetes.

A new UNLV study by a team of chemical biologists, , details a way to selectively route mRNA to the pancreas by using the body's own endogenous pathways—systems responsible for moving materials through the body. The study is titled "Reengineering Endogenous Targeting Lipid Nanoparticles (ENDO) for Systemic Delivery of mRNA to Pancreas."

"Until today, there has been no material that can be injected intravenously that automatically goes to the pancreas with 99% selectivity, an organ previously inaccessible to intravenous treatment," said UNLV biochemistry professor and research lead Chandrabali Bhattacharya. "This discovery is a first."

Most medication options on the market currently target cell receptors throughout the body—rather than specific organs—meaning that very small amounts of administered drugs reach the desired location.

Such pinpoint delivery significantly reduces the likelihood of an immune response or side effects, requiring a lower dose of medicine. It also makes way for significantly reduced long-term treatment costs, especially for chronic conditions such as diabetes.

"Traditional insulin therapy requires lifelong management with recurring expenses," said Ivan Isaac, a UNLV graduate researcher and first author on the study.

"In contrast, mRNA therapies could slow down the loss of insulin, possibly reducing or reversing the disease condition with fewer routine injections."

UNLV's solution is made possible through the patented ENDO, or endogenous targeting lipid nanoparticles, the research team's platform for delivering mRNA to the pancreas.

"We wanted to see how endogenous material, such as Vitamin D, would change the nanoparticles carrying mRNA and interact with the body's pathways," said Bhattacharya.

"These systems can take the particles to different places in the body, and after testing a particular composition of material, we found that it's routing to the pancreas."

The team had figured out that the mechanism through which these nanoparticles go to the pancreas is through the cell surface Vitamin D receptors—essentially the delivery driver of the nanoparticle. Vitamin D receptors are widely distributed throughout the body, but only a few are on the surface of cells. And leveraging that receptor helped route it to specific parts of the body, eventually leading to the pancreas.

"One of the most exciting aspects of this research is its ability to push mRNA therapeutics beyond the liver, expanding treatment options for diseases that haven't been easily addressed with current delivery technologies," said Isaac.

Isaac was deeply involved in developing ENDO and plans to continue working in biopharmaceuticals, creating next-generation drug delivery platforms.

"I hope this work inspires further efforts in precision nanomedicine, where we can improve the safety of our treatments and enhance our tolerance for them," he said.

The researchers are already pursuing further advancements in organ-specific drug delivery to other parts of the body, such as the brain and heart. And both Bhattacharya and Isaac are currently working with UNLV's Office of Economic Development to commercialize the findings.

"It is a colossal stepping stone and foundational block for so much more," said Bhattacharya. "This research has given us a blueprint for the future of medicine."