<p>Messenger RNA therapeutics offer transient protein expression without altering the cellular genome, making them attractive for regenerative medicine, but efficient and safe delivery to the skin remains a major challenge. Lipid nanoparticles have transformed RNA delivery yet can remain limited in skin by tissue accessibility, formulation constraints and local tissue responses. Here we define Biologically Engineered Vectors (BEVs) as biologically assembled delivery particles generated through genetic or cellular engineering to transport therapeutic nucleic acids, and we develop RNA-BEVs as a platform for topical mRNA delivery. RNA-BEVs efficiently delivered functional mRNA to keratinocytes, induced transient protein expression throughout reconstructed epidermis after topical administration, and improved the histological quality of repair relative to mRNA-loaded lipid nanoparticles in a diabetic rat wound model. These findings establish RNA-BEVs as a biologically assembled platform for localized transient RNA delivery and skin regeneration.</p>

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Biologically engineered vectors enable topical mRNA delivery for skin regeneration

  • Julie Gérard,
  • Héloïse Pilet,
  • Charbel Bouez,
  • Xun Du,
  • Yong Chen,
  • Yogeshvar N. Kalia,
  • Pascal Clayette,
  • Bruno A. Bernard,
  • Nicolas Grandchamp

摘要

Messenger RNA therapeutics offer transient protein expression without altering the cellular genome, making them attractive for regenerative medicine, but efficient and safe delivery to the skin remains a major challenge. Lipid nanoparticles have transformed RNA delivery yet can remain limited in skin by tissue accessibility, formulation constraints and local tissue responses. Here we define Biologically Engineered Vectors (BEVs) as biologically assembled delivery particles generated through genetic or cellular engineering to transport therapeutic nucleic acids, and we develop RNA-BEVs as a platform for topical mRNA delivery. RNA-BEVs efficiently delivered functional mRNA to keratinocytes, induced transient protein expression throughout reconstructed epidermis after topical administration, and improved the histological quality of repair relative to mRNA-loaded lipid nanoparticles in a diabetic rat wound model. These findings establish RNA-BEVs as a biologically assembled platform for localized transient RNA delivery and skin regeneration.