title: Impact of the structure of biocompatible aliphatic polycarbonates on siRNA transfection ability.
abstract: RNAi therapeutics are promising therapeutic tools that have sparked the interest of many researchers. In an effort to provide a safe alternative to PEI, we have designed a series of new guanidinium- and morpholino-functionalized biocompatible and biodegradable polycarbonate vectors. The impact of different functions (morpholino-, guanidinium-, hydrophobic groups) of the architecture (linear homopolymer to dumbbell-shape) and of the molecular weight of these copolymers on their capacity to form polyplexes and to decrease the expression of two epigenetic regulators of gene expression, HDAC7 and HDAC5, was evaluated. The use of one of these polymers combining morpholine and guanidine functions at the ratio >1 and hydrophobic trimethylene carbonate groups showed a significant decrease of mRNA and protein level in HeLa cells, similar to PEI. These results highlight the potential of polycarbonate vectors for future in vivo application as an anticancer therapy.
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy - CIRM, §Metastasis Research Laboratory - GIGA, and ∥Protein Signalisation and Interaction - GIGA, University of Liege , Avenue de l'Hopital 1 - 4000, Liege, Belgium.
authors.forename: Antoine
authors.initials: A
authors.lastname: Frère
authors.forename: Michal
authors.initials: M
authors.lastname: Kawalec
authors.forename: Sarah
authors.initials: S
authors.lastname: Tempelaar
authors.forename: Paul
authors.initials: P
authors.lastname: Peixoto
authors.forename: Elodie
authors.initials: E
authors.lastname: Hendrick
authors.forename: Olivier
authors.initials: O
authors.lastname: Peulen
authors.forename: Brigitte
authors.initials: B
authors.lastname: Evrard
authors.forename: Philippe
authors.initials: P
authors.lastname: Dubois
authors.forename: Laetitia
authors.initials: L
authors.lastname: Mespouille
authors.forename: Denis
authors.initials: D
authors.lastname: Mottet
authors.forename: Géraldine
authors.initials: G
authors.lastname: Piel
mesh_terms: D002254:Carbonates / Q000737:chemistry* / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D002254:Carbonates; D011108:Polymers; D034741:RNA, Small Interfering; D006655:Histone Deacetylases