Nucleic Acid-Binding Polymers May Prevent Inflammatory and Autoimmune Diseases

Systemic administration of nucleic acid-binding polymers has been shown to reverse the proinflammatory effect of the extracellular RNAs and DNAs that are released into the circulation by dead and dying cells.

Investigators at Duke University (Durham, NC, USA) were studying how debris from damaged cells inappropriately activated multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). Chronic activation of these TLRs could engender a variety of inflammatory and autoimmune diseases such as lupus, multiple sclerosis, obesity, psoriasis, irritable bowel syndrome, and arthritis.

The investigators evaluated the potential benefits of certain nucleic acid-binding polymers that could entrap extracellular nucleic acids without affecting the nucleic acids present in healthy cells. They reported in the August 23, 2011, issue of the journal Proceedings of the [US] National Academy of Sciences that certain nucleic acid-binding polymers inhibited activation of all nucleic acid-sensing TLRs irrespective of whether they recognized ssRNA (single stranded RNA), dsRNA (double stranded RNA), or hypomethylated DNA. Furthermore, systemic administration of such polymers prevented fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice.

“Depending on the disease, cells that are damaged drive or perpetuate the immune response,” said senior author Dr. Bruce A. Sullenger, professor of surgery at Duke University. “We have shown that we can inhibit that process. Because the inflammatory nucleic acids are outside of cells, whereas DNA and RNA normally function inside cells, we realized that the polymers could bind to the external nucleic acids without disrupting intracellular functions of DNA and RNA. We could use the polymers as molecular scavengers - sponges to go around and soak up and neutralize those inflammatory nucleic acids so the immune system does not recognize them and go into the overdrive of inflammation.”

Patents based on the results of this study have been filed to pave the way for future drug-development efforts. “At some level we have opened up this huge treasure chest of opportunities and now we have to figure out which way to go,” said Dr. Sullenger.

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