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SHR Neuro Cancer Cardio Lipid Metab Microb
Mende, M; Hopert, A; Wünsche, W; Overhoff, M; Detzer, A; Börngen, K; Schlenke, P; Kirchner, H; Sczakiel, G.
A hexanucleotide selected for increased cellular uptake in cis contains a highly active CpG-motif in human B cells and primary peripheral blood mononuclear cells.
Immunology. 2007; 120(2):261-272
Doi: 10.1111/j.1365-2567.2006.02497.x
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- Co-authors Med Uni Graz
- Schlenke Peter
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- Abstract:
- The relationship between immunostimulation of human B cells by cytosine-phosphate-guanosine (CpG) -containing oligonucleotides and their physical cellular uptake is of mechanistic interest and a prerequisite for rational improvements of the therapeutic potential of CpG-harbouring oligonucleotides. Here, a combinatorial approach was used to identify nucleotide sequence motifs that facilitate increased cellular uptake in mammalian cells. Oligonucleotides harbouring the selected hexanucleotide TCGTGT in cis show increased cellular uptake. This motif contains a CpG dinucleotide within a sequence context that shows a very strong CpG-specific stimulatory activity on human B cells. Here we describe the influence of concentration, length and sequence position of the unmethylated CpG dinucleotide on immunostimulation. A comparison between phosphorothioate-derivatives and unmodified TCGTGT-containing oligonucleotides strongly indicates a great CpG-specificity for the unmodified CpG-harbouring oligonucleotides but not for the phosphorothioate versions. This work describes a link between the physical cellular uptake of naked oligonucleotides harbouring the selected cellular uptake motif TCGTGT, its strong CpG-specific stimulation of human B cells and its relationship with the sequence context of CpG and its cellular uptake.
- Find related publications in this database (using NLM MeSH Indexing)
- B-Lymphocytes - immunology B-Lymphocytes - metabolism
- Base Sequence -
- Cells, Cultured -
- Combinatorial Chemistry Techniques -
- CpG Islands - genetics CpG Islands - immunology
- DNA Mutational Analysis -
- Dose-Response Relationship, Immunologic -
- Gene Library -
- Humans -
- Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - metabolism
- Lymphocyte Activation - immunology
- Molecular Sequence Data -
- Oligodeoxyribonucleotides - genetics Oligodeoxyribonucleotides - immunology Oligodeoxyribonucleotides - pharmacokinetics
- Tumor Cells, Cultured -
- Find related publications in this database (Keywords)
- B cells
- cellular uptake
- CpG
- oligonucleotides