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Absence of Unspecific Innate Immune Cell Activation by GATA-3-Specific DNAzymes.
- Source :
-
Nucleic Acid Therapeutics . Apr2012, Vol. 22 Issue 2, p117-126. 10p. - Publication Year :
- 2012
-
Abstract
- DNAzymes of the 10-23 family represent an important class of antisense molecules with implications for therapeutic treatment of diseases. These molecules are single-stranded oligodeoxynucleotides combining the high specificity of oligonucleotide base pairing with an inherent RNA-cleaving enzymatic activity. However, like other oligonucleotide-based molecules these substances might exert so-called off-target effects, which have not been investigated so far for this molecule class. Therefore, the present study investigates putative off-target effects of DNAzymes on innate immune mechanisms using GATA-3-specific DNAzymes that have recently been developed as novel therapeutic approach for the treatment of allergic diseases including allergic asthma. The conserved catalytic domain of 10-23 DNAzymes contains a CpG motif that may stimulate innate immune cells via Toll-like receptor 9 (TLR-9). Therefore, potential TLR-9-mediated as well as TLR-9 independent cell activation was investigated using TLR-9-transfected HEK293 cells, macrophage cell lines and primary innate immune cells. Furthermore, putative effects of GATA-3-specific DNAzymes on the activation of neutrophil granulocytes and degranulation of mast cells/basophils were analyzed. In summary, no innate immune cell-stimulating activities of the tested DNAzymes were observed in any of the systems. Consequently, use of GATA-3-specific DNAzymes may represent a novel and highly specific approach for the treatment of allergic diseases. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 21593337
- Volume :
- 22
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Nucleic Acid Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 85183314
- Full Text :
- https://doi.org/10.1089/nat.2011.0294