title: A high-capacity, hybrid electro-microneedle for in-situ cutaneous gene transfer.
abstract: Cutaneous gene transfer is limited by biological barriers such as skin and cellular membranes; complex approaches are required to overcome these biological barriers, simultaneously. Non-integrated systems that separate cutaneous permeation from intracellular transfection have been used to overcome skin and cellular barriers, respectively, however, do not provide sufficient doses of the gene to local tissue, resulting in inefficient gene transfer in-situ. Although integrated systems for cutaneous gene transfer are available, their safety has been questioned and it is difficult to transfer sufficient amounts of genes due to cumbersome sterilization procedures and the small size of the reservoir. Here, we demonstrate stepwise-aligned cutaneous permeation, cutaneous release, and intracellular transfection using a hybrid electro-microneedle (HEM), which designed as a monolithic hybrid assembly of a dissolving microneedle and an electrode, anomalously. Furthermore, as proof-of-principle, we use the HEM for in-situ cutaneous transfer of p2CMVmIL-12 to successfully treat B16F10 subcutaneous tumors in a mouse model. The HEM described herein holds great promise for cutaneous gene therapy of cancers and for vaccines.
authors.affiliation: Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120 749, Republic of Korea.
authors.forename: Kwang
authors.initials: K
authors.lastname: Lee
authors.forename: Jung Dong
authors.initials: JD
authors.lastname: Kim
authors.forename: Chang Yoel
authors.initials: CY
authors.lastname: Lee
authors.forename: Song
authors.initials: S
authors.lastname: Her
authors.forename: Hyungil
authors.initials: H
authors.lastname: Jung
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004867:Equipment Design; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D018664:Interleukin-12 / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000628:therapy; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D009339:Needles; D012867:Skin / Q000378:metabolism*
chemical_list: D018664:Interleukin-12; D004247:DNA