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K-State Today

September 14, 2017



Checkmate: Researchers find mechanism that could improve therapies for cancer and infectious diseases

By Tiffany Roney

Dhungel and Cao with vaccinia

A finding by Kansas State University researchers could potentially lead to improved targeted therapies for cancer and many viruses.

Messenger RNA is the template to produce proteins in all organisms. Poxviruses, which can infect people, mammals and some reptiles, use a poly(A) leader in their messenger RNA to synthesize more proteins, according to a study published in PLOS Pathogens.

The ability of poxvirus to produce poly(A) leader in its messenger RNA is essential for its survival, according to lead author Pragyesh Dhungel, doctoral student in microbiology.

"These findings are exciting because they hopefully can be used for developing new therapies," Dhungel said.

In the war against some highly dangerous poxviruses, such as smallpox and monkeypox viruses, a poly(A) leader can be a kind of trump card. Human cells do not have or need it, while poxviruses need it to continue synthesizing proteins when the viruses' other synthesizing methods are impeded, according to Dhungel and co-authors Shuai Cao, postdoctoral researcher in biology, and Zhilong Yang, assistant professor of biology.

"If we can stop a poxvirus's use of poly(A) leader, we can kill the virus," Cao said. "This could help develop a novel anti-poxvirus strategy, which could be very important for finding cures for infections and diseases."

This relates to cancer because a poly(A) leader is present in vaccinia virus, which causes little harm in healthy people, is used as a prototype in studying poxviruses and can be engineered to selectively infect cancer cells, Dhungel said.

If biologists add poly(A) leader to any messenger RNA, they can increase the expression of that gene in vaccinia-infected cells, which means a poly(A) leader could potentially be used to improve vaccinia-based cancer therapy in the cells it needs to target, Dhungel said.

"For example, if we use specially engineered vaccinia that overexpresses the channel protein used in the uptake of chemotherapy agents, it will express more of those channels only in the cancer cells," Dhungel said. "By doing so, the cancer cells will take in more of the treatment, allowing the therapy to specifically target cancer cells but leave normal cells alone."

Yang was the principle investigator for this study. The National Institutes of Health and the Johnson Cancer Research Center provided funding for this research.