Ohio State Pharmacy Researchers Awarded NIH Grant

News Release Date: 

Funding Enables Exploration of New Treatment for Liver Cancer

Columbus, Ohio – Two Ohio State University College of Pharmacy faculty will share a $3.2 million grant from the National Institutes of Health to study treatment options for the type of liver cancer known as hepatocellular carcinoma, the third most prevalent cancer in the world.

Thomas Schmittgen, associate professor and chair, and Mitch Phelps, assistant professor, both in the division of pharmaceutics and pharmaceutical chemistry, will study therapeutic RNAs for the treatment of hepatocellular carcinoma, or HCC. The five-year grant from the NIH's Extracellular RNA Communication Common Fund program is one of only 24 awarded nationwide in this initiative.

The Extracellular RNA research will rapidly advance understanding of exRNA. RNA, or ribonucleic acid, is a key regulator of gene activity. Previously thought to reside only within cells, researchers now know that RNA can be exported, serving as an important link in cell-to-cell communication. Investigations funded from this initiative will center on these external, or exRNAs, including potential for using exRNAs as therapeutic molecules.

The research team led by Schmittgen and Phelps will focus on using exRNA to develop a novel type of cancer treatment based on a new class of biomolecules called microRNA, which serve as a very specific control point for how a gene operates.

According to Schmittgen, certain microRNAs normally function to suppress tumor growth. Yet in some cancers, including HCC, their absence contributes to the development of tumors. The grant will allow Schmittgen and Phelps to experiment with treating HCC by replenishing microRNA-199, a specific microRNA that is often decreased in HCC tumors, in the liver.

Currently, RNA’s instability in the body has impeded efforts to effectively use this molecule as a drug. Therefore, therapeutic RNAs require some type of drug delivery system in order to be effective.

The grant comprises two phases. In the first phase, Schmittgen and Phelps will load therapeutic microRNA-199 into microvesicles, naturally occurring bodies that are shed from various cells. The design to synthesize and package microRNA-199 into microvesicles was developed in Schmittgen’s laboratory in 2012.

“This delivery method has three important features: enhanced drug stability, targeting to the tumor and production of the RNA drug by the same cells that produce the microvesicles,” Schmittgen said. “Since therapeutic RNAs are costly to synthesize, it is our hope that natural production and packaging of the RNA into microvesicles may someday be affordable and mainstream.”

In the second phase, the researchers will investigate the ability of the microvesicles to find their target within the body. Notes Phelps: “As with all new therapies, we need to learn how these microvesicles will be distributed to various organs and tissues and how effectively they achieve their intended purpose, which in this case is to destroy HCC tumors in the liver.”

NIH Common Funds support high-impact programs aimed at freeing roadblocks to scientific discovery. The grants leverage emerging scientific opportunities across multiple biomedical fields, so that transformative human health advances can be made swiftly and effectively. 

HCC is the most common of liver cancers. According to the National Cancer Institute, some 31,640 new cases of HCC will be diagnosed in the United States this year. The prognosis for HCC is poor, with only a 10- to 20-percent survival rate.

The Ohio State team of investigators involved in the exRNA project includes Melissa Piper, Chenglong Li, Michael Paulaitis, Tracey Papenfuss and Xiaokui Mo.

About The Ohio State University College of Pharmacy

Established in 1885, The Ohio State University College of Pharmacy is a global leader in pharmaceutical education, research and clinical practice. As part of one of the most comprehensive health sciences campus in the nation, the college is home to world-class faculty, dedicated researchers and top students who are leading the way in pharmacy education, practice and research. The college’s graduate programs are currently ranked 7th in the nation by U.S. News & World Report. Connect with us on Facebook, Twitter and LinkedIn, or learn more at http://www.pharmacy.ohio-state.edu/

About The Ohio State University

Founded in 1870, The Ohio State University is a world-class public research university and the leading comprehensive teaching and research institution in the state of Ohio. With more than 63,000 students (including 56,000 in Columbus), the Wexner Medical Center, 14 colleges, 80 centers, and 168 majors, the university offers its students tremendous breadth and depth of opportunity in the liberal arts, the sciences, and the professions.