Advanced healthcare materialsApr 21, 2026

Using Shellac to Build Nanoparticles for Delivering mRNA

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Shellac-stabilized nanoparticles may reduce the usual tradeoff between mRNA transfection efficiency and polymer toxicity.

Evidence

A formulation and platform study tested shellac-based mRNA nanoparticles across cell types and in mice, reporting >90% encapsulation, transfection with negligible cytotoxicity, and protein expression or gene editing after intravenous and oral dosing.

Caveat

The evidence is limited to platform performance in cells and mice, not disease treatment, durable expression, immune safety, or human outcomes.

Simplified

Cationic polymers have been extensively explored for messenger RNA (mRNA) delivery owing to their ability to condense nucleic acids and facilitate cellular uptake. High-molecular-weight polymers typically achieve high transfection efficiency but exhibit substantial cytotoxicity, whereas low-molecular-weight polymers show reduced cytotoxicity but low transfection efficiency. To address the tradeoff between toxicity and transfection efficiency, herein, we present a simple and versatile shellac (SL)-mediated assembly strategy, whereby mRNA is complexed with low-molecular-weight cationic polymers (e.g., polyethyleneimine) and subsequently stabilized by SL to form nanoparticles under mild conditions. The SL-based nanoparticles exhibit >90% mRNA encapsulation efficiency and enable mRNA transfection across various cell types while showing negligible cytotoxicity. Furthermore, the SL-based nanoparticle platform enables protein expression and gene editing in mice through both intravenous and oral administration routes. This work highlights the potential of SL as a key building block to direct the assembly and delivery of mRNA, enabling the rational design of modular and versatile nucleic acid delivery platforms for diverse biological applications.