Downregulation of the p75 neurotrophin receptor in tissue culture and in vivo, using β-cyclodextrin-adamantane-oligonucleotide conjugates

Abstract

Formation of complexes with β-cyclodextrin derivatives via adamantyl groups was found to entrance the up-take and antisense efficacy of phosphorothioate oligos targeted to the p75 neurotrophin receptor in neuronally differentiated PC12 cells. After a 2-week course of systemic administration to mice (by intraperitoneal injection), there was evidence of a pronounced uptake of these oligos by the dorsal root ganglia (DRG), as well as by liver and kidney. There was no uptake by the brain. Consistent with uptake of antisense oligos by the DRG, systemic administration resulted in marked and consistent downregulation of p75 in DRG neurons. These results indicate that cyclodextrin-adamantane-oligo c..