Rabies virus-mimicking liposomes for targeted gene therapy in Alzheimer's disease

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dc.authorid0000-0003-3287-5277
dc.authorid0000-0001-9273-6346
dc.authorid0000-0002-4175-4402
dc.authorid0000-0001-7062-0684
dc.authorid0000-0002-7587-7443
dc.contributor.authorErel Akbaba, Gulsah
dc.contributor.authorAkbaba, Hasan
dc.contributor.authorKaraman, Ozan
dc.contributor.authorTian, Tian
dc.contributor.authorTannous, Bakhos A.
dc.contributor.authorTurunc, Ezgi
dc.date.accessioned2025-03-13T10:59:37Z
dc.date.available2025-03-13T10:59:37Z
dc.date.issued2024
dc.departmentEge Üniversitesi, Eczacılık Fakültesi
dc.description.abstractRNA interference (RNAi) harbors significant potential for treating neurological disorders; nevertheless, limited efficacy has been discerned. The presence of barriers within the central nervous system, coupled with the inherent instability of nucleic acids within biological conditions, poses formidable challenges in advancing effective gene delivery strategies. In this study, we designed and prepared a virus-mimic non-viral gene vector, rabies virus glycoprotein (RVG29)-decorated liposome (f(Lipo)-RVG29), to deliver small interfering RNAs to the brain. Alzheimer's disease (AD) was chosen as a model of neurodegenerative disease in this context, and b-site APP cleaving enzyme silencing siRNA (siBACE1) was used. The developed liposomal delivery system has a particle size of under 80 nm with a spherical shape, positive zeta potential, and the ability to protect siRNA against nucleases. In vitro studies demonstrate that functionalizing the cationic liposome by the RVG29 targeting ligand significantly enhances the effectiveness of gene delivery and silencing. Examination through ex vivo imaging illustrates an increased deposition of fluorescent-labeled f(Lipo)-RVG29 within brain tissue after 12 h post application. Additionally, the in vivo delivery of f(Lipo)-RVG29 carrying siRNA has substantially suppressed BACE1 expression at both mRNA and protein levels within the brain tissue. Our results suggest that the developed non-viral vector could be a promising gene carrier system combining the synergistic effect of virus-mimic RVG29 ligand with bioinspired liposome that imitates the natural lipid bilayers of cell membranes for braintargeted RNAi therapeutics.
dc.identifier.citationErel-Akbaba, G., Akbaba, H., Karaman, O., Tian, T., Tannous, B. A., & Turunc, E. (2025). Rabies virus-mimicking liposomes for targeted gene therapy in Alzheimer’s disease. International Journal of Pharmaceutics, 668, 124962.
dc.identifier.doi10.1016/j.ijpharm.2024.124962
dc.identifier.endpage13
dc.identifier.issn0378-5173
dc.identifier.issueDec
dc.identifier.pmid39592065
dc.identifier.scopus2-s2.0-85210138209
dc.identifier.scopusqualityQ1
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.1016/j.ijpharm.2024.124962
dc.identifier.urihttps://hdl.handle.net/11454/116673
dc.identifier.volume668
dc.identifier.wosWOS:001373080400001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorAkbaba, Hasan
dc.institutionauthorid0000-0001-9273-6346
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofInternational Journal of Pharmaceutics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAlzheimer's disease
dc.subjectBACE1
dc.subjectRVG29
dc.subjectsiRNA
dc.subjectVirus-mimic liposome
dc.titleRabies virus-mimicking liposomes for targeted gene therapy in Alzheimer's disease
dc.typeArticle

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