Topical Delivery of siRNA-Based Spherical Nucleic Acid Nanoparticle Conjugates for Gene Regulation*
Topical application of nucleic acids offers many potential therapeutic advantages for suppressing genes in the skin, and potentially for systemic gene delivery. However, the epidermal barrier typically precludes entry of gene-suppressing therapy unless the barrier is disrupted. This chapter shows that spherical nucleic acid nanoparticle conjugates (SNA-NCs), gold cores surrounded by a dense shell of highly oriented, covalently immobilized siRNA, freely penetrate almost 100 percent of keratinocytes in vitro, mouse skin, and human epidermis within hours after application. It hypothesizes that siRNA-based SNA gold nanoparticle conjugates might be ideal topical delivery agents to treat diseases of the skin. The chapter presents data that provide compelling evidence of RNAi-mediated gene suppression in vivo after topical application to intact skin of siRNAs delivered without the need for additional physical measures, keratolytics, or peptides to enhance penetration.