title: Nucleic acid delivery systems based on poly(galactosyl ureaethyl methacrylate-b-dimethylamino ethyl methacrylate) diblock copolymers.
abstract: Elevated low-density-lipoprotein cholesterol (LDL-C) level is a major risk factor leading to cardiovascular diseases. Therefore, since the proprotein convertase subtilisin kexin type 9 (PCSK9) regulates LDL-C receptors, it represents the appropriate target for cholesterol-lowering gene therapy. However, although delivery of antisense oligonucleotides (ODNs) is a promising therapeutic method for the treatment of several diseases, it is fundamental to develop new and efficacious carriers that transport the ODNs into the target cell in a nontoxic manner. This study reports on the synthesis, characterization and in vitro testing of a new liver specific carrier based on linear cationic diblock glycopolymer composed of galactosyl ureaethyl methacrylate (GAMA) and the primary amine-containing dimethylamino ethyl methacrylate (DMAEMA). Delivery experiments proved that the poly(galactosyl ureaethyl methacrylate -b-dimethylamino ethyl methacrylate) diblock copolymer (pGa4D47), internalized in a receptor-mediated manner, exhibited a much faster nuclear transportation than ODNs carried by pDMAEMA homopolymer or glycopolymer bearing glucose moieties.
authors.affiliation: Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.
authors.forename: M C
authors.initials: MC
authors.lastname: Munisso
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: obika@phs.osaka-u.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Obika
authors.affiliation: Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan. Electronic address: yamtet@ri.ncvc.go.jp.
authors.forename: T
authors.initials: T
authors.lastname: Yamaoka
mesh_terms: D002470:Cell Survival; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates / Q000737:chemistry; D009696:Nucleic Acids / Q000008:administration & dosage* / Q000737:chemistry*; D009757:Nylons / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D008689:Methacrylates; D009696:Nucleic Acids; D009757:Nylons; D011108:Polymers; C407037:poly(2-(dimethylamino)ethyl methacrylate); C049840:2-(dimethylamino)ethyl methacrylate
keywords: Antisense; Galactosyl ureaethyl methacrylate; Hepatocyte; Non-viral gene carrier; PSCK9