Quick nuclear transportation of siRNA and in vivo hepatic ApoB gene silencing with galactose-bearing polymeric carrier.

Since previous studies have linked the genetic mutations of Apolipoprotein B (ApoB) to the low density lipoprotein (LDL) cholesterol levels, it can be believed that the knockdown of ApoB by siRNA silencing is a useful method to reduce the cardiovascular disease. However, the spontaneous uptake of siRNA is hindered, and thus vectors are necessary to aid its transfer into the cells. Among the synthetic non-viral vectors, cationic polymers are extensively investigated as possible candidates for efficient and specific gene delivery, because they can be easily modified to get different set of properties.

Effects of CC chemokine receptor 5 (CCR5) inhibitors on the dynamics of CCR5 and CC-chemokine-CCR5 interactions.

Background: This study aimed to examine how CC chemokine receptor 5 (CCR5) inhibitors (aplaviroc [APL], TAK779 and maraviroc [MVC]) interact with CCR5 and affect its dynamics and physiological CC-chemokine-CCR5 interactions.

Methods: A yellow fluorescent protein (YFP)-tagged CCR5-expressing U373-MAGI cell line was generated and a stable CCR5-expressing clonal population, (YFP)CCR5-UM16, was prepared. (YFP)CCR5-UM16 cells were exposed to RANTES, macrophage inflammatory protein (MIP)-1alpha or MIP-1beta (all 100 ng/ml) with or without CCR5 inhibitors and (YFP)CCR5 internalization was visualized with real-time by laser scanning confocal microscopy.

Liver-targeted siRNA delivery by polyethylenimine (PEI)-pullulan carrier.

Recently, small interfering RNA (siRNA)-based therapeutics have been used to treat diseases. Efficient and stable siRNA delivery into disease cells is important in the use of this agent for treatment. In the present study, pullulan was introduced into polyethylenimine (PEI) for liver targeting.