Development of a novel RNAi therapy:Engineered miR-31 exosomes promoted the healing of diabetic wounds  

作　　者：Jinghuan Huang Muyu Yu Wenjing Yin Bo Liang Ang Li Jingfeng Li Xiaolin Li Shichang Zhao Fang Liu 

机构地区：[1]Department of Orthopaedic Surgery,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,China [2]Department of Endocrinology and Metabolism,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,China [3]Department of Orthopedics,Zhongnan Hospital of Wuhan University,China

出　　处：《Bioactive Materials》2021年第9期2841-2853,共13页生物活性材料（英文）

基　　金：The authors acknowledge the support of the National Natural Science Foundation of China(81572178,81270397,81702317,81871752 and 81770802);the National Key R&D Program of China(2017YFC1309601 to Fang Liu);Shanghai Municipal Commission of Health and Family Planning under the fund(20124356);a Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant(20152232).

摘　　要：Rationale:Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment.Exosome therapy is an extension of stem cell therapy,and RNA interference(RNAi)-based therapy is a type of advanced precision therapy.Based on the discovery of chronic wound-related genes in diabetes,we combined exosome therapy and RNAi therapy through an engineering approach for the treatment of diabetic chronic wounds.Methods:We combined exosome therapy and RNAi therapy to establish a precision therapy for diabetes-associated wounds via an engineered exosome approach.Results:First,chronic diabetic wounds express low levels of miR-31-5p compared with nondiabetic wounds,and an miR-31-5p mimic was shown to be effective in promoting the proliferation and migration of three wound-related cell types in vitro.Second,bioinformatics analysis,luciferase reporter assays and western blotting suggested that miR-31-5p promoted angiogenesis,fibrogenesis and reepithelization by inhibiting factor-inhibiting HIF-1(HIF1AN,also named FIH)and epithelial membrane protein-1(EMP-1).Third,engineered miR-31 exosomes were generated as a miR-31-5p RNAi therapeutic agent.In vivo,the engineered miR-31 exosomes promoted diabetic wound healing by enhancing angiogenesis,fibrogenesis and reepithelization.Conclusion:Engineered miR-31 exosomes are an ideal disease pathophysiology-initiated RNAi therapeutic agent for diabetic wounds.

关 键 词：Engineered exosomes Diabetes chronic wounds RNAi therapy miR-31-5p Precision therapy 

分 类 号：R587.1[医药卫生—内分泌]