Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy

The success of messenger RNA therapeutics largely depends on the availability of delivery systems that enable the safe, effective and stable translation of genetic material into functional proteins. Here we show that extracellular vesicles (EVs) produced via cellular nanoporation from human dermal fibroblasts, and encapsulating mRNA encoding for extracellular-matrix alpha 1 type-I collagen (COL1A1) induced the formation of collagen-protein grafts and reduced wrinkle formation in the collagen-depleted dermal tissue of mice with photoaged skin. We also show that the intradermal delivery of the mRNA-loaded EVs via a microneedle array led to the prolonged and more uniform synthesis and replacement of collagen in the dermis of the animals. The intradermal delivery of EV-based COL1A1 mRNA may make for an effective protein-replacement therapy for the treatment of photoaged skin.

Automated summary

The study found that extracellular vesicles (EVs) produced through cellular nanoporation can safely and effectively translate genetic material into functional proteins. In mice with photoaged skin, EVs carrying mRNA encoding for collagen induced collagen-protein grafts and reduced wrinkle formation. Intradermal delivery of mRNA-loaded EVs through a microneedle array resulted in prolonged and more uniform synthesis and replacement of collagen in the dermis. Intradermal delivery of EV-based COL1A1 mRNA may be an effective protein-replacement therapy for treating photoaged skin.