title: Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery.
abstract: Skin is an attractive target for delivery of genetic therapies and vaccines. However, new approaches are needed to access this tissue more effectively. Here, we describe a new delivery technology based on arrays of structurally precise, micron-scale silicon projections, which we term microenhancer arrays (MEAs). In a human clinical study, these devices effectively breached the skin barrier, allowing direct access to the epidermis with minimal associated discomfort and skin irritation. In a mouse model, MEA-based delivery enabled topical gene transfer resulting in reporter gene activity up to 2,800-fold above topical controls. MEA-based delivery enabled topical immunization with naked plasmid DNA, inducing stronger and less variable immune responses than via needle-based injections, and reduced the number of immunizations required for full seroconversion. Together, the results provide the first in vivo use of microfabricated devices to breach the skin barrier and deliver vaccines topically, suggesting significant clinical and practical advantages over existing technologies.
authors.affiliation: BD Technologies, Research Triangle Park, North Carolina, USA. john_mikszta@bd.com
authors.forename: John A
authors.initials: JA
authors.lastname: Mikszta
authors.forename: Jason B
authors.initials: JB
authors.lastname: Alarcon
authors.forename: John M
authors.initials: JM
authors.lastname: Brittingham
authors.forename: Diane E
authors.initials: DE
authors.lastname: Sutter
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Pettis
authors.forename: Noel G
authors.initials: NG
authors.lastname: Harvey
mesh_terms: D000818:Animals; D019470:Biolistics; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007114:Immunization / Q000379:methods*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D012867:Skin / Q000276:immunology*
chemical_list: D008156:Luciferases