Scientists identify antibiotics to enhance gene-silencing tool

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London, July 21 : A class of antibiotics, known as fluoroquinolones can enhance RNA interference, the gene-silencing tool that can treat a variety of diseases if adapted in humans, say researchers at Emory University.

The researchers have said that the antibiotics can make RNA interference more effective in the laboratory and reduce potential side effects.

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

Enoxacin was found to be the most powerful enhancer of RNA interference which has been used to treat gonorrhea and urinary tract infections. This particular group of compounds also includes the widely used antibiotic ciprofloxacin.

However, it seems that the antibiotics' effect on RNA interference is chemically separate from their bacteria-killing activities. Still, Jin said that significant barriers prevent RNA interference from working well in people

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

Earlier studies have found that side effects result depending on the amount of RNA injected, which can trigger an anti-viral response, instead of the genetic sequence of the RNA used.

The 2006 Nobel Prize in Medicine went to Andrew Fire and Craig Mello 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.

In order to know the working of RISC, the researchers inserted a gene for a fluorescent protein into a cell line, and later 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.

It was 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.

The results will be published online in the journal Nature Biotechnology.

ANI

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