title: Reducible hyaluronic acid-siRNA conjugate for target specific gene silencing.
abstract: Despite wide applications of polymer-drug conjugates, there are only a few polymer-siRNA conjugates like poly(ethylene glycol) conjugated siRNA. In this work, reducible hyaluronic acid (HA)-siRNA conjugate was successfully developed for target specific systemic delivery of siRNA to the liver. The conjugation of siRNA to HA made it possible to form a compact nanocomplex of siRNA with relatively nontoxic linear polyethyleneimine (LPEI). After characterization of HA-siRNA conjugate by size exclusion chromatography (SEC) and gel electrophoresis, its complex formation with LPEI was investigated with a particle analyzer. The HA-siRNA/LPEI complex had a mean particle size of ca. 250 nm and a negative or neutral surface charge at physiological condition. The reducible HA-siRNA/LPEI complex showed a higher in vitro gene silencing efficiency than noncleavable HA-siRNA/LPEI complex. Furthermore, after systemic delivery, apolipoprotein B (ApoB) specific HA-siApoB/LPEI complex was target specifically delivered to the liver, which resulted in statistically significant reduction of ApoB mRNA expression in a dose dependent manner. The HA-siRNA conjugate can be effectively applied as a model system to the treatment of liver diseases using various siRNAs and relatively nontoxic polycations.
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), San 31 Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Korea.
authors.forename: Kitae
authors.initials: K
authors.lastname: Park
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Yang
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Hwiwon
authors.initials: H
authors.lastname: Lee
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
mesh_terms: D001483:Base Sequence; D002850:Chromatography, Gel; D017931:DNA Primers; D020868:Gene Silencing; D006820:Hyaluronic Acid / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry*
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D006820:Hyaluronic Acid