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Liposome-based Formulation for Intracellular Delivery of Functional Proteins

dc.contributor.authorCHATIN, Benoit
dc.contributor.authorMEVEL, Mathieu
dc.contributor.authorDEVALLIERE, Julie
dc.contributor.authorDALLET, Laurence
dc.contributor.authorHAUDEBOURG, Thomas
dc.contributor.authorPEUZIAT, Pauline
dc.contributor.authorCOLOMBANI, Thibault
dc.contributor.authorBERCHEL, Mathieu
dc.contributor.authorLAMBERT, Olivier
dc.contributor.authorEDELMAN, Aleksander
dc.contributor.authorPITARD, Bruno
dc.date.accessioned2020-09-03T08:02:16Z
dc.date.available2020-09-03T08:02:16Z
dc.date.issued2015
dc.identifier.issn2162-2531
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/11002
dc.description.abstractEnThe intracellular delivery of biologically active protein represents an important emerging strategy for both fundamental and therapeutic applications. Here, we optimized in vitro delivery of two functional proteins, the beta-galactosidase (beta-gal) enzyme and the anti-cytokeratin8 (K8) antibody, using liposome-based formulation. The guanidinium-cholesterol cationic lipid bis (guanidinium)-tren-cholesterol (BGTC) (bis (guanidinium)-tren-cholesterol) combined to the colipid dioleoyl phosphatidylethanolamine (DOPE) (dioleoyl phosphatidylethanolamine) was shown to efficiently deliver the beta-gal intracellularly without compromising its activity. The lipid/protein molar ratio, protein amount, and culture medium were demonstrated to be key parameters affecting delivery efficiency. The protein itself is an essential factor requiring selection of the appropriate cationic lipid as illustrated by low K8 binding activity of the anti-K8 antibody using guanidinium-based liposome. Optimization of various lipids led to the identification of the aminoglycoside lipid dioleyl succinyl paromomycin (DOSP) associated with the imidazole-based helper lipid MM27 as a potent delivery system for K8 antibody, achieving delivery in 67% of HeLa cells. Cryo-transmission electron microscopy showed that the structure of supramolecular assemblies BGTC: DOPE/beta-gal and DOSP: MM27/K8 were different depending on liposome types and lipid/protein molar ratio. Finally, we observed that K8 treatment with DOSP: MM27/K8 rescues the cyclic adenosine monophosphate (cAMP)-dependent chloride efflux in F508del-CFTR expressing cells, providing a new tool for the study of channelopathies.
dc.language.isoen
dc.title.enLiposome-based Formulation for Intracellular Delivery of Functional Proteins
dc.typeArticle de revue
dc.identifier.doi10.1038/mtna.2015.17
dc.subject.halChimie/Matériaux
bordeaux.journalMolecular Therapy-Nucleic Acids
bordeaux.volume4
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248*
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN, UMR 5248)
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular%20Therapy-Nucleic%20Acids&rft.date=2015&rft.volume=4&rft.eissn=2162-2531&rft.issn=2162-2531&rft.au=CHATIN,%20Benoit&MEVEL,%20Mathieu&DEVALLIERE,%20Julie&DALLET,%20Laurence&HAUDEBOURG,%20Thomas&rft.genre=article


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