Document Type

Article

Publication Date

2021

Publication Title

Pharmaceutics

Volume

13

Issue

11

Pages

1908 (1-20)

DOI

10.3390/pharmaceutics13111908

Abstract

Gene-based approaches for protein replacement therapies have the potential to reduce the number of administrations. Our previous work demonstrated that expression could be enhanced and/or the applied voltage reduced by preheating the tissue prior to pulse administration. In the current study, we utilized our 16-pin multi-electrode array (MEA) and incorporated nine optical fibers, connected to an infrared laser, between each set of four electrodes to heat the tissue to 43 °C. For proof of principle, a guinea pig model was used to test delivery of reporter genes. We observed that when the skin was preheated, it was possible to achieve the same expression levels as gene electrotransfer without preheating, but with a 23% reduction of applied voltage or a 50% reduction of pulse number. With respect to expression distribution, preheating allowed for delivery to the deep dermis and muscle. This suggested that this cutaneous delivery approach has the potential to achieve expression in the systemic circulation, thus this protocol was repeated using a plasmid encoding Human Factor IX. Elevated Factor IX serum protein levels were detected by ELISA up to 100 days post gene delivery. Further work will involve optimizing protein levels and scalability in an effort to reduce application frequency.

Comments

© 2021 by the authors

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) license.

Original Publication Citation

Edelblute, C., Mangiamele, C., & Heller, R. (2021). Moderate heat-assisted gene electrotransfer as a potential delivery approach for protein replacement therapy through the skin. Pharmaceutics, 13(11), 1-20, Article 1908. https://doi.org/10.3390/pharmaceutics13111908

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