A Pliable Electroporation Patch (ep-Patch) for Efficient Delivery of Nucleic Acid Molecules into Animal Tissues with Irregular Surface Shapes

Abstract

Delivery of nucleic acids into animal tissues by electroporation is an appealing approach for various types of gene therapy, but efficiency of existing methodsis not satisfactory. Here we present the validation of novel electroporation patch (ep-Patch) for efficient delivery of DNA and siRNA into mouse tissues. Using micromachining technology, closely spaced gold electrodes were made on the pliable parylene substrate to form a patch-like electroporation metrics. It enabled large coverage of the target tissues and close surface contact between the tissues and electrodes, thus providing a uniform electric field to deliver nucleic acids into tissues, even beneath intact skin. Using this ep-Patch for efficiently delivery of both DNA and siRNA, non-invasive electroporation of healthy mouse muscle tissue was successfully achieved. Delivery of these nucleic acids was performed to intact tumors with satisfactory results. Silencing of tumor genes using the ep-Patch was also demonstrated on mice. This pliable electroporation patch method constitutes a novel way of in vivo delivery of siRNA and DNA to certain tissues or organs to circumvent the disadvantages of existing methodologies for in vivo delivery of nucleic acid molecules.

Electrotransfer of siRNA to Silence Enhanced Green Fluorescent Protein in Tumor Mediated by a High Intensity Pulsed Electromagnetic Field

“…Thus, the local delivery approach, i.e., electroporation, may have advantages over systemic delivery in accessible tumors. Successful gene silencing in different cells and tissues was obtained by using conventional electroporation as non-viral delivery approach of siRNA targeting reporter or therapeutic genes [5,21,[39][40][41][42][43][44]. Silencing therapeutic CD105 (endoglin), VEGF and Rho GTPase Rac1 genes demonstrated good antitumor and antivascular effects [5,21,45].…”

Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery

“…Another common permeation assistant strategy is the use of electroporation [36][37][38][39]. Electroporation employs a pair of electrodes than can be attached to the skin (Fig.…”

Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis

“…However, the effectiveness of topically administered therapeutic nucleic acids is often diminished by low permeation efficiency across the skin due to the pertinent protective physical barriers, including the stratum corneum, nucleated epidermal layers, and tight junctions [ 10 ]. Several previous studies have reported that, not only the physical methods, such as electroporation, microneedles, or iontophoresis [ 11 , 12 , 13 , 14 ], but also nanocarriers, such as liposome, polymer or carbon nanotube, are capable of penetrating siRNAs in animal skin [ 15 , 16 , 17 ]. Additionally, one expected method of improving siRNAs permeation efficiency is the use of the cell penetrating peptides, including the arginine-rich transcriptional activator (TAT)-derived peptides [ 18 , 19 , 20 , 21 , 22 , 23 ].…”