Reducible Hyaluronic Acid-siRNA Conjugate for Target Specific Gene Silencing
SCIE
SCOPUS
- Title
- Reducible Hyaluronic Acid-siRNA Conjugate for Target Specific Gene Silencing
- Authors
- Park, K; Yang, JA; Lee, MY; Lee, H; Hahn, SK
- Date Issued
- 2013-07
- Publisher
- AMER CHEMICAL SOC
- 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 non-toxic 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.
- Keywords
- IN-VIVO; LINEAR POLYETHYLENIMINE; INTRACELLULAR DELIVERY; SYSTEMIC DELIVERY; RNA INTERFERENCE; COMPLEX; DNA; MICE; THERAPEUTICS; DERIVATIVES
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/15079
- DOI
- 10.1021/BC4001257
- ISSN
- 1043-1802
- Article Type
- Article
- Citation
- BIOCONJUGATE CHEMISTRY, vol. 24, no. 7, page. 1201 - 1209, 2013-07
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