title: Systemic delivery of transthyretin siRNA mediated by lactosylated dendrimer/α-cyclodextrin conjugates into hepatocyte for familial amyloidotic polyneuropathy therapy.
abstract: RNA interference (RNAi) is a sequence-specific gene-silencing mechanism triggered by double-stranded RNA and powerful tools for a gene function study and RNAi therapy. Although siRNAs offer several advantages as potential new drugs to treat various diseases, the efficient delivery system of siRNAs in vivo remains a crucial challenge for achieving the desired RNAi effect in clinical development. In particular, when considering the siRNA therapeutics for familial amyloidotic polyneuropathy (FAP) caused by the deposition of variant transthyretin (TTR) in various organs, hepatocyte-selective siRNA delivery is desired because TTR is predominantly synthesized by hepatocytes. In this study, to reveal the potential use of lactosylated dendrimer (G3)/α-cyclodextrin conjugate (Lac-α-CDE (G3)) as novel hepatocyte-selective siRNA carriers in order to treat FAP, we evaluated the RNAi effect of siRNA complex with Lac-α-CDE (G3) both in vitro and in vivo.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Mori
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Dinah W Y
authors.initials: DW
authors.lastname: Sah
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000628:therapy*; D000818:Animals; D050091:Dendrimers / Q000737:chemistry*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D011228:Prealbumin / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D047391:alpha-Cyclodextrins / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D011228:Prealbumin; D034741:RNA, Small Interfering; D047391:alpha-Cyclodextrins; C032613:alpha-cyclodextrin