PloS oneJul 7, 2026

A Piezoelectric Device for Improved Delivery of RNA Vaccines Without Carriers

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 8, 2026

Abstract

A simple and inexpensive electroporator can enhance gene expression and immune response to naked mRNA, achieving comparable effectiveness to lipid nanoparticles at low doses.

Naked mRNA delivery has traditionally been limited by rapid degradation and poor cellular uptake.
The Piezopen device utilizes microneedle electrodes for skin-targeted delivery of mRNA, self-amplifying RNA, and circular RNA.
Administration of naked mRNA with Piezopen resulted in robust immune responses without systemic inflammation.
Cross-species validation in live human skin suggests potential for safe clinical application.
Piezopen may serve as a cost-effective alternative to lipid nanoparticles for routine vaccinations and pandemic responses.

Simplified

Despite the success of COVID-19 mRNA vaccines, they still face challenges with high costs, complex manufacturing, off-target biodistribution, and systemic reactogenicity stemming from their inflammatory carriers: lipid nanoparticles (LNPs). While "naked" RNA delivery could in principle solve these issues, studies have suggested that it is infeasible due to rapid degradation by RNases and poor cellular entry, thereby necessitating formulations that enhance intracellular delivery and RNA stability. Now, we challenge this paradigm by showing that a simple and inexpensive (<$1), lighter-derived electroporator with microneedle electrodes (Piezopen) can augment gene expression and immunogenicity to naked mRNA leading to comparable responses to LNPs at low doses. We achieve robust responses in the absence of systemic inflammation and reactogenicity using skin-targeted delivery, administer diverse construct types (i.e., mRNA, self-amplifying RNA (saRNA), circular RNA (circRNA)), and demonstrate cross-species validation in live human skin to derisk subsequent clinical application. Our results introduce Piezopen as an inexpensive, well-tolerated, and efficacious alternative to LNPs for mRNA vaccine delivery, designed to facilitate routine vaccinations and pandemic response.

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Funding

Competing interests

All authors are employees of Piezo Therapeutics, Inc., a for-profit company developing the Piezopen platform described in this manuscript. E.M. and G.B. are named inventors on filed, granted, or licensed patents pertaining to the Piezopen technology. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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A $1 device delivers naked mRNA vaccines as effectively as lipid nanoparticles in mice and human skin

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A Piezoelectric Device for Improved Delivery of RNA Vaccines Without Carriers

Abstract

Full Text

Funding

Competing interests

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