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Gene healing in a lotion? Researchers say they're close

Most people who buy cosmetic lotions and potions know that while the people working behind the department store makeup counters may wear white lab coats, the stuff they sell is more about packaging than science.

But a Northwestern University team is bucking that image, reporting today that they’ve created a way to regulate genes affecting the skin -- merely by applying moisturizer.

Not only could their technology pave the way for cosmetics that actually work, but it also might also prove to be a valuable weapon in fighting melanoma, the deadliest form of skin cancer, or diseases like psoriasis, and wounds like the intractable sores that often plague diabetics.

“This is a blockbuster in the ways we will treat diseases of the skin,” said Chad Mirkin, director of the International Institute for Nanotechnology and the George B. Rathmann Professor of Chemistry at Northwestern said. “We’re talking about ailments, scarring, wound healing, ways of regulating them or retarding them.”

In a research paper published today in the Proceedings of the National Academy of Sciences, Mirkin and his colleagues describe not a drug, exactly, but a way of delivering small sections of nucleic acids (DNA and RNA are nucleic acids) called short interfering RNA, or siRNA, to cells. The cells take up the siRNA, which then alters the way a gene inside each cell can be read by the protein-making system.

The team used gold particles with a diameter of 13 nanometers. (One nanometer is 1-billionth of a meter. A typical strand of human hair is roughly 60,000 nanometers wide.) They coated the particles with siRNA to create what they call “spherical nucleic acid nanoparticle conjugates,” or SNAs. Millions of SNAs were then added to a commercially available petroleum-based skin moisturizer and the mixture was applied to mice and to lab-grown human skin.  

In their key experiment in mice, they used their new system to tamp down the activity of a gene called epidermal growth factor receptor, or EGFR, that’s involved in the growth of melanoma. As its name implies, EGFR receives messages from the epidermal growth factor protein. So toning down EGFR will interrupt the message; growth will be reduced or stop.

After mice were treated with the mixture three times per week for three weeks, the expression of the EGFR gene was reduced by 65 percent.

'Impressive' results
Steve Dowdy, professor of cellular and molecular medicine at the University of California San Diego, and a Howard Hughes Medical Institute investigator specializing in RNA inhibition and ways to deliver siRNAs, called that result “impressive.” 

But EGFR was just a proof-of-principle target. The delivery system could, in theory, carry targeted siRNA to regulate any number of genes, including ones related to skin aging.

Mirkin’s enthusiasm for the possibilities of the new therapy is rare. It’s unusual for a scientist to rave about his work in such terms, especially one in the field of siRNA, which has a checkered history filled with scientific frustrations and failed companies.

Ten years ago, scientists predicted a new era of siRNA therapies, but the hype machine ran into a roadblock: how to deliver siRNAs into cells and make them regulate the target gene and not cause any collateral damage.

The issue mainly has been size, Dowdy explained. Two million years of evolution have created cells that do a good job of keeping foreign stuff out. In order to enter a cell passively, a substance has to be about 1 nanometer or less, one reason why small molecule drugs -- pills -- are so tough to create. Another problem is that cell membranes carry a negative charge. They repel negatively charged molecules, like siRNAs. 

“It’s like trying to squeeze an elephant through the top of your desk,” Dowdy said.

Mirkin explained that his team’s delivery system relies on so-called “scavenger receptors” on the cell surface to grab the nano SNAs and gobble them up. Once the SNAs were inside the cell, they were able to begin silencing the EGFR gene.

Dowdy said he’s “cautious” about Mirkin’s claims for SNAs, given the history of other delivery systems that have been tried. So far no solution has been perfect, though siRNA technology is being tested in human clinical trials. 

Another issue is the nanospheres themselves. For example, the Food and Drug Administration has yet to rule on the use of nanoparticles in sunscreens until more data can be gathered on what effects, if any, the particles might have if they pass through skin and enter the bloodstream. Last week, the agency announced that the tiny technology needs more safety testing before it can be used in consumer goods.

But Dowdy did agree that for use on skin -- especially in cases like psoriasis or diabetic wounds where the skin surface has already been compromised, Mirkin’s group may be onto something.

Mirkin certainly hopes so. He’s founded a company called Aurasense Therapeutics. Just as Botox was originally meant to be used for muscle disorders, but now makes heaps of money thanks to its wrinkle-fighting properties, Aurasense stands to reap a windfall if anybody can walk up to a counter and buy a lotion or cream that really will reduce the signs of aging.

“I’ve never been more excited about anything,” Mirkin said.

Still, whether nano-delivered gene regulation is going to be the next Botox remains to be seen.

Brian Alexander (www.BrianRAlexander.com) is co-author, with Larry Young PhD., of "The Chemistry Between Us: Love Sex and the Science of Attraction," (www.TheChemistryBetweenUs.com)  to be published Sept. 13.

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