Delivery of self-replicating messenger RNA into the brain for the treatment of ischemic stroke
DC Field | Value | Language |
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dc.contributor.author | Kim, Minkyung | - |
dc.contributor.author | Oh, Jungju | - |
dc.contributor.author | Lee, Youngki | - |
dc.contributor.author | Lee, Eun-Hye | - |
dc.contributor.author | Ko, Seung Hwan | - |
dc.contributor.author | Jeong, Ji Hoon | - |
dc.contributor.author | Park, Chang Hwan | - |
dc.contributor.author | Lee, Minhyung | - |
dc.date.accessioned | 2022-10-25T06:56:55Z | - |
dc.date.available | 2022-10-25T06:56:55Z | - |
dc.date.created | 2022-10-06 | - |
dc.date.issued | 2022-10 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/172527 | - |
dc.description.abstract | Ischemic stroke is caused by the occlusion of cerebral arteries. In the ischemic stroke, ischemia-reperfusion injury increases the damage in the brain after reperfusion. In the previous study, heme oxygenase-1 (HO1) mRNA was delivered into the ischemic brain, showing that HO1-mRNA had higher therapeutic effect and less side-effect than HO1-plasmid (pHO1). However, mRNA is degraded faster than plasmid DNA reducing the duration of gene expression. In this study, self-replicating mRNA (Rep-mRNA) was developed using a replicon system from Venezuelan Equine Encephalitis virus to compensate this disadvantage of mRNA delivery. Deoxycholic acid-conjugated polyethylenimine (DA-PEI) was used as a carrier of the mRNAs. The Rep-mRNA/DA-PEI complex had a size of around 90 nm and a zeta-potential of 33 mV. In the in vitro transfection assays, gene expression by the HO1-Rep-mRNA/DA-PEI complex persisted at least 14 days, while that by the HO1-mRNA/DA-PEI complex approached basal level at 3 days after transfection. Therapeutic effects of the HO1-Rep-mRNA/DA-PEI complexes were evaluated in the ischemic stroke animal model. The complexes were injected into the brain stereotaxically. HO1 expression by the HO1-Rep-mRNA/DA-PEI complex persisted at least 7 days after injection, but the pHO1/DA-PEI or HO1-mRNA/DA-PEI complex showed basal level of HO1-expression at 7 days after injection. Due to higher and longer expression of HO1, the apoptosis level and infarct size were decreased by the HO1-Rep-mRNA/DA-PEI complexes, compared with the pHO1/DA-PEI and HO1-mRNA/DA-PEI complex. These results suggest that HO1-Rep-mRNA/DA-PEI complex may have a potential as a long-lasting therapeutic system for the treatment of ischemic stroke. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER | - |
dc.title | Delivery of self-replicating messenger RNA into the brain for the treatment of ischemic stroke | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Chang Hwan | - |
dc.contributor.affiliatedAuthor | Lee, Minhyung | - |
dc.identifier.doi | 10.1016/j.jconrel.2022.08.049 | - |
dc.identifier.scopusid | 2-s2.0-85137081108 | - |
dc.identifier.wosid | 000858631200001 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CONTROLLED RELEASE, v.350, pp.471 - 485 | - |
dc.relation.isPartOf | JOURNAL OF CONTROLLED RELEASE | - |
dc.citation.title | JOURNAL OF CONTROLLED RELEASE | - |
dc.citation.volume | 350 | - |
dc.citation.startPage | 471 | - |
dc.citation.endPage | 485 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | HEME OXYGENASE-1 GENE | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | HMGB1 | - |
dc.subject.keywordAuthor | Self -replicating mRNA | - |
dc.subject.keywordAuthor | Ischemic stroke | - |
dc.subject.keywordAuthor | Gene delivery | - |
dc.subject.keywordAuthor | Gene therapy | - |
dc.subject.keywordAuthor | Ischemia-reperfusion | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0168365922005569?via%3Dihub | - |
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