Transdermal delivery of antisense compounds

Antisense technology holds tremendous promise for therapeutic applications and the study of gene function. A broadly applicable route of administration that would provide for non-invasive, simple, and convenient delivery is highly desirable. Application of oligonucleotides to the skin may represent a solution to the delivery question for both local treatment of skin disease and for systemic delivery. The iontophoretic mode of delivery for phosphorothioate oligonucleotides across hairless mouse skin reveals the potential limitation in the delivery of sufficient oligonucleotide to provide for efficacy. A potential solution to this problem is the use of significantly more potent C-5 propyne base modifications in a phosphorothioate oligonucleotide. The combination of the iontophoretic delivery mode with potent oligonucleotides resulted in selective inhibition of the CYP3A2 gene expression in the rat liver. Alternatively, oligomers with neutral charge combined with passive modes of transdermal delivery may also be feasible and represent an even more broadly applicable technology. Future studies will focus on specific applications of local and systemic therapy of antisense oligonucleotide in animal models for the design of treatment regimens.