Topical delivery of nucleic acids in the skin

The skin is an attractive site for the delivery of nucleic acid-based drugs for the treatment of topical and/or systemic diseases as well as for DNA immunization. However, due to the barrier properties of the skin, the penetration of nucleic acids in or across the skin is limited. This review focuses on the chemical, biological or physical methods developed to enhance nucleic acid delivery into the skin. Oligonucleotides have been delivered across the skin using iontophoresis. Potentially therapeutic concentrations were reached in hair follicles using liposomes and in keratinocytes using electroporation. In vivo transfer of genetic material to the skin has been achieved experimentally using dermal injection, topical application of naked DNA, DNA/lipids complexes or viral vectors as well as particle bombardment, puncturing or electroporation of plasmid DNA. Protein expression has been detected in the skin and/or the serum. The localization and duration of expression was affected by the delivery methods. The remaining challenges to address for optimal in vivo gene delivery in the skin are i) duration of expression (more than 1 to 4 weeks for the treatment of inherited skin and systemic diseases requesting protein supplementation), ii) delivery methods (if progress has been achieved, a safe, efficient, patient-friendly, non-invasive method for long-term expression at a high level in the target cells and extensive body area of a patient has not yet been developed), iii) targeted delivery.