Design of Liposome Formulations for CRISPR/Cas9 Enzyme Immobilization: Evaluation of 5-Alpha-Reductase Enzyme Knockout for Androgenic Disorders

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dc.authoridErel-Akbaba, Gulsah/0000-0003-3287-5277
dc.authoridSenturk, Serif/0000-0003-3963-2294
dc.authorscopusid57190564982
dc.authorscopusid57200229272
dc.authorscopusid24482896800
dc.authorscopusid12545373100
dc.authorwosidErel-Akbaba, Gulsah/JTU-8732-2023
dc.authorwosidSenturk, Serif/A-1263-2017
dc.contributor.authorAkbaba, Hasan
dc.contributor.authorErel-Akbaba, Gülsah
dc.contributor.authorBaspinar, Yucel
dc.contributor.authorŞentürk, Şerif
dc.date.accessioned2024-08-25T18:51:35Z
dc.date.available2024-08-25T18:51:35Z
dc.date.issued2023
dc.departmentEge Üniversitesien_US
dc.description.abstractThe enzyme steroid type II 5-alpha-reductase (SRD5 alpha 2) is responsible for the conversion of testosterone to dihydrotestosterone (DHT), which is involved in prostate cancer, benign prostatic hyperplasia, and androgenic alopecia. Inhibition of SRD5 alpha 2 activity has been explored and presented as a potential treatment for these conditions, but current drugs have side effects and alternative treatment approaches are needed. The CRISPR/Cas9 system, an innovative gene-editing tool, shows potential for targeting the SRD5 alpha 2 gene knockout as a therapeutic approach. Liposomes have been used for the immobilization and delivery of different proteins, and studies have shown that liposomes can enhance the stability and activity of enzymes. In this study, we provided the immobilization of Cas9 protein by encapsulating it in a novel cationic liposome formulation that carries sgRNA on its outer surface for gene delivery approaches. This novel delivery system has shown promising results in terms of physicochemical properties, stability, cytotoxicity, in vitro cellular uptake, and gene knockout efficiency, together with providing flexibility in sgRNA selection. The optimized final formulations showed an average diameter of 229.1 +/- 3.66 nm, a polydispersity index of 0.089 +/- 0.013, and a zeta potential value of 25.7 +/- 0.87 mV. The encapsulation efficiency of the developed formulations has been revealed as 80.60%. The cellular uptake efficiency was evaluated and measured as 45.6% for the final formulation. Furthermore, the Lipo/Cas9:sgRNA (1.5:1) formulation decreased the relative SRD5 alpha 2 mRNA expression by 29.7% compared to the control group. The results of this study reveal that the liposomal formulation based on enzyme immobilization of Cas9 protein using CRISPR technology, an innovative gene-editing tool for SRD5 alpha 2 suppression, might be an alternative treatment option for prostate cancer or BPH treatment without current drug side effects.en_US
dc.description.sponsorshipT?rkiye Bilimsel ve Teknolojik Arastirma Kurumu [22487]; Ege University Scientific Research Projects Coordination Unit [SBAG-218S682]; Scientific and Technological Research Council of Turkeyen_US
dc.description.sponsorshipThis work was supported by Ege University Scientific Research Projects Coordination Unit (project no.: 22487) and The Scientific and Technological Research Council of Turkey (grant no.: SBAG-218S682).en_US
dc.identifier.doi10.1021/acsomega.3c07138
dc.identifier.endpage46112en_US
dc.identifier.issn2470-1343
dc.identifier.issue48en_US
dc.identifier.pmid38075788en_US
dc.identifier.scopus2-s2.0-85179164517en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage46101en_US
dc.identifier.urihttps://doi.org/10.1021/acsomega.3c07138
dc.identifier.urihttps://hdl.handle.net/11454/102611
dc.identifier.volume8en_US
dc.identifier.wosWOS:001114440300001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Chemical Socen_US
dc.relation.ispartofAcs Omegaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240825_Gen_US
dc.subjectBenign Prostatic Hyperplasiaen_US
dc.subjectSolid Lipid Nanoparticlesen_US
dc.subjectCas9 Proteinen_US
dc.subjectDeliveryen_US
dc.subjectInhibitorsen_US
dc.subjectGeneen_US
dc.subjectRibonucleoproteinen_US
dc.subjectComplexesen_US
dc.subjectSystemsen_US
dc.subjectCanceren_US
dc.titleDesign of Liposome Formulations for CRISPR/Cas9 Enzyme Immobilization: Evaluation of 5-Alpha-Reductase Enzyme Knockout for Androgenic Disordersen_US
dc.typeArticleen_US

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