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
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
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. July 2008.