Gene-regulation technology to fight skin cancer and other diseases has the potential to be delivered right through the skin in the form of a moisturizer, recent research has demonstrated.
The topical application of nucleic acids could offer many therapeutic advantages for suppressing genes in the skin and possibly for systemic gene delivery, explained Amy S. Paller, MD, and colleagues in Proceedings of the National Academy of the Sciences of the United States of America (2012;109:11975-11980). However, the epidermal barrier typically doesn’t allow for the entry of gene-suppressing therapy.
Paller, who is the chair of dermatology at Northwestern University Feinberg School of Medicine in Evanston, Illinois, and the director of Northwestern’s Skin Disease Research Center, collaborated with Northwestern chemist Chad A. Mirkin and others at the facility to break the skin barrier. They showed that drugs consisting of spherical nucleic acid nanoparticle conjugates (SNA-NCs), which are gold cores surrounded by a dense shell of small interfering RNA (siRNA), can freely penetrate human epidermis within hours after application. The structures can be delivered in a commercial moisturizer or a phosphate-buffered saline.
Once the agent has crossed into the skin, it can selectively target and abolish the epidermal growth factor receptor (EGFR) gene while sparing normal genes.
“This allows us to treat a skin problem precisely where it is manifesting—on the skin,” commented Paller in a statement issued by Northwestern University. “We can target our therapy to the drivers of disease, at a level so minute that it can distinguish mutant genes from normal genes.”
According to the researchers, risks are minimal and side effects have not been seen in human skin or in mouse models. After 3 weeks of topical skin treatment, the SNA structures were virtually undetectable in internal organs.
Early targets of the novel treatment are melanoma and squamous cell carcinoma as well as psoriasis, diabetic wound healing, and the rare genetic skin disorder, epidermolytic ichthyosis. The therapy may even prove to be an effective treatment for wrinkles.