Dr. Amy Paller Awarded Grant from FIRST
Dr. Amy Paller Awarded FIRST Grant
The research of Dr. Paller’s project entitled Topical delivery of keratin 10 mutation-specific siRNA-gold nanoparticles for epidermolytic ichthyosis was approved for a $75,000 grant for the 2012 Research Grant Program. The object of Dr. Paller’s project states that epidermolytic ichthyosis (EI) is an inherited form of ichthyosis which manifests as blistering and the compensatory development of generalized scaling skin. These skin changes usually result from a change in a single base of DNA of one copy of the gene encoding either keratin 1 or keratin 10, thus disrupting the ability of the keratin to provide structural integrity to the epidermal cells. Small interfering RNAs (siRNAs) are able to distinguish normal from abnormal genes at a single base level and suppress only the abnormal gene, but getting siRNAs through skin after topical application has been difficult. We have recently engineered a novel conjugate, in which siRNAs densely surround a central gold nanoparticle (spherical siRNA-Au NPs). The resulting conjugate siRNAs are able to penetrate through skin after application in ointment, are easily taken up into epidermal cells, and are much more effective at suppressing protein expression in primary keratinocytes than lipofected siRNA. To date, no adverse effects have been seen from use of the siRNA-Au NPs in cultured human cells or in mouse models.
How is this work relevant to the Foundation for Ichthyosis & Related Skin Types?
Given the previously demonstrated ability of these siRNA-Au NPs to distinguish RNA at the point mutation level, this non-viral, topically applied gene therapy holds great promise for mutation-specific treatment of epidermolytic ichthyosis. Although our model is EI, it should be mentioned that this topically-applied siRNA-Au NP approach is applicable to other dominant-negative ichthyotic disorders, such as connexin defects (e.g., KID syndrome) and epidermolytic palmoplantar keratodermas. Furthermore, the models developed in the proposed investigations will be useful for studying the molecular basis for EI and developing screening tests for hot-spot mutations that facilitate personalized therapy.
Dr. Amy Paller is the Walter J. Hamlin Professor and Chair of Dermatology and Professor of Pediatrics at Northwestern University's Feinberg School of Medicine.