Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy.
Yi YouYu TianZhaogang YangJunfeng ShiKwang Joo KwakYuhao TongAndreanne Poppy EstaniaJianhong CaoWei-Hsiang HsuYutong LiuChi-Ling ChiangBenjamin R SchrankKristin M HuntoonDaeYong LeeZiwei LiYarong ZhaoHuan ZhangThomas D GallupJongHoon HaShiyan DongXuefeng LiYifan WangWen-Jing LuEman BahraniLy James LeeLesheng TengWen JiangFeng LanYon Son Betty KimAndrew S LeePublished in: Nature biomedical engineering (2023)
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 α1 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.
Keyphrases
- drug induced
- wound healing
- extracellular matrix
- replacement therapy
- binding protein
- tissue engineering
- endothelial cells
- smoking cessation
- drug delivery
- type diabetes
- high resolution
- gene expression
- amino acid
- dna methylation
- mass spectrometry
- copy number
- skeletal muscle
- genome wide
- high throughput
- diabetic rats
- induced pluripotent stem cells
- high glucose
- pluripotent stem cells
- high density