Electroporation-enhanced delivery of nucleic acid vaccines

Abstract

The naked delivery of nucleic acid vaccines is notoriously inefficient, and an enabling delivery technology is required to direct efficiently these constructs intracellularly. A delivery technology capable of enhancing nucleic acid uptake in both cells in tissues and in culture is electroporation (EP). EP is a physical delivery mechanism that increases the permeability of mammalian cell membranes and allows the trafficking of large macromolecules into the cell. EP has now been used extensively in the clinic and been shown to be an effective method to increase both the uptake of the construct and the breadth and magnitude of the resulting immune responses. Excitingly, 2014 saw the announcement of the first EP-enhanced DNA vaccine Phase II trial demonstrating clinical efficacy. This review seeks to introduce the reader to EP as a technology to enhance the delivery of DNA and RNA vaccines and highlight several published clinical trials using this delivery modality.

Keywords:

• DNA vaccine
• electroporation
• electrotransfer
• RNA vaccine

Acknowledgements

We would like to thank A Gomez and A Slager for manuscript assistance.

Financial & competing interests disclosure

Both of the authors are current employees of Inovio and as such have financial interest (in the form of salary compensation, stock options and/or stock ownership) in the work described in this review article.

Key issues

• Multiple trials demonstrating the safety and tolerability of electroporation (EP) as an enhancing delivery technology for DNA vaccines exist in the literature.

• DNA vaccines combined with EP have been extensively shown to generate robust immune responses both preclinically and clinically over naked delivery alone.

• Multiple DNA-based cancer vaccines combined with EP have been and are being evaluated in the clinic.

• Multiple DNA-based vaccines against a range of infectious diseases combined with EP have been and are being evaluated in the clinic.

• The combination of a therapeutic DNA vaccine and EP was shown to elicit clinical efficacy in a Phase II trial.

• Self-replicating RNA vaccines are a promising technology, but clinical data are lacking. The entry of this technology into the clinic is likely to be soon, but a delivery technology will be required.