Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesions

IntroductionDespite the protection and management of skin has been paid more and more attention, effective countermeasures are still lacking for patients suffering from UV or chemotherapy with damaged skin. Recently, gene therapy by small interfering RNA (siRNA) has emerged as a new therapeutic stra...

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Main Authors: Wei Lu, Jinzhong Zhang, Yungang Wu, Wenxue Sun, Zipei Jiang, Xu Luo
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1109381/full
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author Wei Lu
Jinzhong Zhang
Yungang Wu
Wenxue Sun
Zipei Jiang
Xu Luo
Xu Luo
Xu Luo
Xu Luo
author_facet Wei Lu
Jinzhong Zhang
Yungang Wu
Wenxue Sun
Zipei Jiang
Xu Luo
Xu Luo
Xu Luo
Xu Luo
author_sort Wei Lu
collection DOAJ
description IntroductionDespite the protection and management of skin has been paid more and more attention, effective countermeasures are still lacking for patients suffering from UV or chemotherapy with damaged skin. Recently, gene therapy by small interfering RNA (siRNA) has emerged as a new therapeutic strategy for skin lesions. However, siRNA therapy has not been applied to skin therapy due to lack of effective delivery vector.MethodsHere, we develop a synthetic biology strategy that integrates the exosomes with artificial genetic circuits to reprogram the adipose mesenchymal stem cell to express and assemble siRNAs into exosomes and facilitate in vivo delivery siRNAs for therapy of mouse models of skin lesions.ResultsParticularly, siRNA enriched exosomes (si-ADMSC-EXOs) could be directly taken up by the skin cells to inhibit the expression of skin injury related genes. When mice with skin lesions were smeared with si-ADMSC-EXOs, the repair of lesioned skin became faster and the expression of inflammatory cytokines were decreased.DiscussionOverall, this study establishes a feasible therapeutic strategy for skin injury, which may offer an alternative to conventional biological therapies requiring two or more independent compounds.
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spelling doaj.art-874a7a95c1394c03beb3197e5ae708762023-02-08T06:48:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11093811109381Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesionsWei Lu0Jinzhong Zhang1Yungang Wu2Wenxue Sun3Zipei Jiang4Xu Luo5Xu Luo6Xu Luo7Xu Luo8The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaThe Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of the Orthopedics of Traditional Chinese Medicine (TCM), the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaHemodialysis Room, Department of Nephrology, the First Hospital Affiliated of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Ophthalmology, the First Hospital Affiliated of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaWenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Wounds and Burns, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaKey Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaZhejiang Engineering Research Center for Hospital Emergency and Process Digitization, Wenzhou, Zhejiang, ChinaIntroductionDespite the protection and management of skin has been paid more and more attention, effective countermeasures are still lacking for patients suffering from UV or chemotherapy with damaged skin. Recently, gene therapy by small interfering RNA (siRNA) has emerged as a new therapeutic strategy for skin lesions. However, siRNA therapy has not been applied to skin therapy due to lack of effective delivery vector.MethodsHere, we develop a synthetic biology strategy that integrates the exosomes with artificial genetic circuits to reprogram the adipose mesenchymal stem cell to express and assemble siRNAs into exosomes and facilitate in vivo delivery siRNAs for therapy of mouse models of skin lesions.ResultsParticularly, siRNA enriched exosomes (si-ADMSC-EXOs) could be directly taken up by the skin cells to inhibit the expression of skin injury related genes. When mice with skin lesions were smeared with si-ADMSC-EXOs, the repair of lesioned skin became faster and the expression of inflammatory cytokines were decreased.DiscussionOverall, this study establishes a feasible therapeutic strategy for skin injury, which may offer an alternative to conventional biological therapies requiring two or more independent compounds.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1109381/fullengineeredsiRNAexosomesUVskin lesionstherapy
spellingShingle Wei Lu
Jinzhong Zhang
Yungang Wu
Wenxue Sun
Zipei Jiang
Xu Luo
Xu Luo
Xu Luo
Xu Luo
Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesions
Frontiers in Immunology
engineered
siRNA
exosomes
UV
skin lesions
therapy
title Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesions
title_full Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesions
title_fullStr Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesions
title_full_unstemmed Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesions
title_short Engineered NF-κB siRNA-encapsulating exosomes as a modality for therapy of skin lesions
title_sort engineered nf κb sirna encapsulating exosomes as a modality for therapy of skin lesions
topic engineered
siRNA
exosomes
UV
skin lesions
therapy
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1109381/full
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