title: Amido-bridged nucleic acids with small hydrophobic residues enhance hepatic tropism of antisense oligonucleotides in vivo.
abstract: High scalability of a novel bicyclic nucleoside building block, amido-bridged nucleic acid (AmNA), to diversify pharmacokinetic properties of therapeutic antisense oligonucleotides is described. N2'-functionalization of AmNA with a variety of hydrophobic groups is straightforward. Combinations of these modules display similar antisense knockdown effects and improve cellular uptake, relative to sequence-matched conventional 2',4'-bridged nucleic acid (2',4'-BNA) in vivo.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. obika@phs.osaka-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Aiko
authors.initials: A
authors.lastname: Yahara
authors.forename: Reiko
authors.initials: R
authors.lastname: Waki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yasuhara
authors.forename: Fumito
authors.initials: F
authors.lastname: Wada
authors.forename: Mariko
authors.initials: M
authors.lastname: Harada-Shiba
authors.forename: Satoshi
authors.initials: S
authors.lastname: Obika
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D053305:Apolipoprotein C-III / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D057927:Hydrophobic and Hydrophilic Interactions; D008099:Liver / Q000378:metabolism*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000588:Amines; D053305:Apolipoprotein C-III; D016376:Oligonucleotides, Antisense; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; C434331:phosphoramidite