ScienceDaily (July 2, 2012) Getting under your skin takes on a brave new meaning thanks to Northwestern University research that could transform gene regulation.

A team led by a physician-scientist and a chemist -- from the fields of dermatology and nanotechnology -- is the first to demonstrate the use of commercial moisturizers to deliver gene regulation technology that has great potential for life-saving therapies for skin cancers.

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

Applied directly to the skin, the drug penetrates all of the skins layers and can selectively target disease-causing genes while sparing normal genes. Once in cells, the drug simply flips the switch of the troublesome genes to off.

A detailed study of a method that could dramatically redefine the field of gene regulation will be published online during the week of July 2 by the Proceedings of the National Academy of Sciences (PNAS).

Early targets of the novel treatment are melanoma and squamous cell carcinoma (two of the most common types of skin cancer), the common inflammatory skin disorder psoriasis, diabetic wound healing and a rare genetic skin disorder that has no effective treatment (epidermolytic ichthyosis). Other targets could even include wrinkles that come with aging skin.

The technology developed by my collaborator Chad Mirkin and his lab is incredibly exciting because it can break through the skin barrier, said co-senior author Amy S. Paller, M.D., the Walter J. Hamlin Professor, chair of dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine. She also is director of Northwesterns Skin Disease Research Center.

This allows us to treat a skin problem precisely where it is manifesting -- on the skin, she said. We can target our therapy to the drivers of disease, at a level so minute that it can distinguish mutant genes from normal genes. Risks are minimized, and side effects have not been seen to date in our human skin and mouse models.

A co-senior author of the paper, Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering. He also is the director of Northwesterns International Institute for Nanotechnology.

Mirkin first developed the nanostructure platform used in this study in 1996 at Northwestern, and the FDA-cleared technology now is the basis of powerful commercialized medical diagnostic tools. This, however, is the first realization that the nanostructures naturally enter skin and that they can deliver a large payload of therapeutics.

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Breaking the skin barrier: Drugs topically deliver gene therapy via commercial moisturizers for skin disease treatment

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