DUARTE, Calif., October 31, 2008 — City of Hope researchers have confirmed that microRNA, short segments of RNA also known as miRNA, have a greater role in turning on and off genes in the nucleus of cells than previously thought. miRNA, which serve as regulators in the body of the cell to keep activated genes in control, can also target and control genes at earlier stages of activity in the nucleus. The study by John Rossi, Ph.D., Lidow Family Reseach Chair at City of Hope and senior investigator on the study, and colleagues, was published in the October 21 edition of the journal Proceedings of the National Academy of Sciences  (PNAS).

In a process commonly referred to as gene expression, specific areas of DNA are activated to produce proteins or other molecules that signal cells to manufacture more molecules. Previous research had established that miRNA primarily controls the amount of protein created through gene expression at the tail end of the process on the molecules produced in the cytoplasm bodies of cells. Rossi’s research confirmed that miRNA also acts on the DNA in the nucleus of the cell, at the beginning stages of gene expression.

“We are one of the first labs to demonstrate that endogenous miRNA can target and silence genes in mammals,” said Rossi. “We identified 10 examples of miRNA that are fully complementary to promoter regions. There are even more if we look at partial matches.”

The basis for gene therapy is the introduction of a modified gene that can alter how the patient’s own DNA functions in order to treat the genetic source of a disease. Modified versions of small RNA, such as miRNA, can be introduced into a system and create changes. These miRNA are foreign to the cell and are categorized as exogenous. Not much was known about the function of endogenous miRNA that originate from within the cells themselves, though, especially on gene expression in the nucleus.

“The more we understand how a system works, the better we can develop more targeted therapies for genetic diseases like cancer,” said Rossi.

Rossi is a leading researcher in the field of RNA interference as the basis for gene therapy. Short strands of RNA, such as miRNA, can be engineered to turn specific genes on or off to affect a disease. He has developed a novel anti-HIV therapy built on siRNA technology currently in early stage clinical trials that may help kill off HIV as well as enable patients to create new white blood cells resistant to HIV infection.