Class of antibiotics can enhance gene-silencing tool

July 20, 2008

A way to turn off one gene at a time has earned acceptance in biology laboratories over the last decade. Doctors envision the technique, called RNA interference, as a tool to treat a variety of diseases if it can be adapted to humans.

Emory University researchers have discovered that antibiotics known as fluoroquinolones can make RNA interference more effective in the laboratory and reduce potential side effects. The results will be published online this week in the journal Nature Biotechnology.

"The surprising aspect is that some fluoroquinolones have this previously unrecognized property," says senior author Peng Jin, PhD, assistant professor of human genetics at Emory University School of Medicine. "The good part is that doctors have years of experience treating bacterial infections with them, so they are generally considered safe."

The most powerful enhancer of RNA interference was enoxacin, which has been used to treat gonorrhea and urinary tract infections. The group of compounds also includes the widely used antibiotic ciprofloxacin. The antibiotics' effect on RNA interference appears to be chemically separate from their bacteria-killing activities.

Significant barriers still prevent RNA interference from working well in people, Jin says.

"The barriers include specificity and toxicity, as well as getting the RNA to the right place in the body," he says. "If we can enhance how potent a given amount of RNA is and reduce dosage, we're tackling both specificity and toxicity."

Some studies have found that side effects come from the amount of RNA injected, which can trigger an anti-viral response, rather than from the genetic sequence of the RNA used.

Andrew Fire and Craig Mello received the 2006 Nobel Prize in Medicine for their discovery that short pieces of RNA, when introduced into cells, can silence a stretch of genetic code. Artificially introduced RNA hijacks machinery inside the cell called the RNA-induced silencing complex or RISC.

To probe how RISC works, Jin and his co-workers inserted a gene for a fluorescent protein into a cell line, and then added a short piece of RNA that incompletely silences the inserted gene. That way, if a potential drug tweaked the silencing process, the researchers could see it quickly.

They found that enoxacin can increase how well a gene is silenced by up to a factor of ten in cultured cells and by a factor of three in mice. It appears to strengthen the grip of part of RISC, a protein called TRBP, upon small pieces of RNA.

Source: Emory University

Explore further: Using light to control genome editing

Related Stories

Using light to control genome editing

August 25, 2016

The genome-editing system known as CRISPR allows scientists to delete or replace any target gene in a living cell. MIT researchers have now added an extra layer of control over when and where this gene editing occurs, by ...

Study identifies new target for treatment of melanoma

August 4, 2016

A Brazilian study shows that inhibition of an RNA named RMEL3, which is encoded by a previously uncharacterized gene (also named RMEL3), can reduce the viability of cultured melanoma cells by up to 95%.

Researchers unlock new CRISPR system for targeting RNA

June 2, 2016

Researchers from the Broad Institute of MIT and Harvard, Massachusetts Institute of Technology, the National Institutes of Health, Rutgers University- New Brunswick and the Skolkovo Institute of Science and Technology have ...

Recommended for you

New method developed for producing some metals

August 25, 2016

The MIT researchers were trying to develop a new battery, but it didn't work out that way. Instead, thanks to an unexpected finding in their lab tests, what they discovered was a whole new way of producing the metal antimony—and ...

ALMA finds unexpected trove of gas around larger stars

August 25, 2016

Astronomers using the Atacama Large Millimeter/submillimeter Array (ALMA) surveyed dozens of young stars—some Sun-like and others approximately double that size—and discovered that the larger variety have surprisingly ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.