Biologically engineered vectors enable topical mRNA delivery for skin regeneration
Abstract
Messenger RNA (mRNA) therapeutics enable transient protein expression without altering the cellular genome, making them attractive for regenerative medicine. However, efficient and safe delivery to the skin is still challenging. Lipid nanoparticles (LNPs) have enabled major advances in RNA delivery, but in skin their performance is often limited by tissue accessibility, formulation constraints and local tissue responses. In parallel, biologically assembled delivery systems - including viral vectors, engineered extracellular vesicles and virus-like particles - have expanded, but remain constrained by challenges in cargo control, particle heterogeneity and biosafety, while lacking a unified conceptual framework. Here we introduce Biologically Engineered Vectors (BEVs) as a class of biologically assembled delivery particles generated through genetic or cellular engineering to transport therapeutic nucleic acids. Within this class, we developed reverse-transcription-deficient BEVs (rtBEVs) derived from lentiviral particles engineered to prevent RNA-to-DNA conversion and genomic integration. rtBEVs efficiently delivered functional mRNA to keratinocytes, induced protein expression throughout reconstructed epidermis after topical administration, and improved the histological quality of repair relative to mRNA-loaded LNPs in a diabetic rat wound model.
Citation Information
@article{nicolasgrandchamp2026,
title={Biologically engineered vectors enable topical mRNA delivery for skin regeneration},
author={Nicolas Grandchamp and Julie Gerard and Heloise Pilet and Charbel Bouez and Xu Du and Yong Chen and Yogeshvar Kalia and Pascal Clayette and Bruno Bernard},
journal={Research Square},
year={2026},
doi={https://doi.org/10.21203/rs.3.rs-9293588/v1}
}
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