Polyguanosine motif increases cellular oligonucleotide uptake in the brain cortex.
Cellular uptake and localization of fluorescein isothiocyanate-labelled or biotin-labelled CpG-oligonucleotides (oligonucleotides containing unmethylated CpG dinucleotides within specific flanking bases) with or without 3'-end continuous guanosines (polyG motif) were studied in the rat cortex. Twenty minutes after intracerebral microinjection, labelled CpG-oligonucleotide accumulated in both nuclear and cytoplasmic compartments of neuronal and nonneuronal cells localized near the injection site. In the brain, polyG motif significantly increased the cellular uptake of phosphodiester CpG-oligonucleotide (P < 0.05) but not phosphothioate CpG-oligonucleotide (P > 0.05). These data not only provide in-vivo evidence for the local uptake and distribution of oligonucleotides in the brain cortex but also indicate that phosphodiester CpG-oligonucleotides containing a 3'-end polyG motif show an increased cellular uptake and thus might be promising alternate analogues for application to the brain.
Zhang
Zhiren
Z
Institute of Brain Research, University of Tuebingen, Tuebingen, Germany. zhangzhiren@yahoo.com
Fauser
Uwe
U
Schluesener
Hermann J
HJ
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D001710:Biotin / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D008845:Microinjections / Q000379:methods; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew
C408982:CPG-oligonucleotide; D007211:Indoles; D009838:Oligodeoxyribonucleotides; C007293:DAPI; D001710:Biotin