title: Surface Plasmon Resonance Assay of Binding Properties of Antisense Oligonucleotides to Serum Albumins and Lipoproteins.
abstract: In the present study, we developed an assay to evaluate the kinetic binding properties of the unconjugated antisense oligonucleotide (ASO) and lipophilic and hydrophilic ligands conjugated ASOs to mouse and human serum albumin, and lipoproteins using surface plasmon resonance (SPR). The lipophilic ligands conjugated ASOs showed clear affinity to the albumins and lipoproteins, while the unconjugated and hydrophilic ligand conjugated ASOs showed no interaction. The SPR method showed reproducible immobilization of albumins and lipoproteins as ligands on the sensor chip, and reproducible affinity kinetic parameters of interaction of ASOs conjugated with the ligands could be obtained. The kinetic binding data of these ASOs to albumin and lipoproteins by SPR were related with the distributions in the whole liver in mice after administration of these conjugated ASOs. The results demonstrated that our SPR method could be a valuable tool for predicting the mechanism of the properties of delivery of conjugated ASOs to the organs.
authors.affiliation: Pharmaceutical Research Division, Shionogi & Co., Ltd.
authors.forename: Reina
authors.initials: R
authors.lastname: Onishi
authors.forename: Ayahisa
authors.initials: A
authors.lastname: Watanabe
authors.forename: Mado
authors.initials: M
authors.lastname: Nakajima
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Kugimiya
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kinouchi
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Nihashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamimori
mesh_terms: D000116:Acetylgalactosamine / Q000737:chemistry*; D000818:Animals; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D020349:Surface Plasmon Resonance / Q000379:methods*
chemical_list: D008024:Ligands; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D016376:Oligonucleotides, Antisense; D012709:Serum Albumin; D000116:Acetylgalactosamine