Document Detail


Brief communication: stability and catalytic activity of novel circular DNAzymes.
MedLine Citation:
PMID:  16898416     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DNAzymes represent a new generation of catalytic nucleic acids for specific RNA targeting in order to inhibit protein translation from the specifically cleaved mRNA. The 10-23 DNAzyme was found to hydrolyze RNA in a sequence-specific manner both in vitro and in vivo. Although single-stranded DNAzymes may represent the most effective nucleic acid drug to date, they are nevertheless sensitive to nuclease degradation and require modifications for in vivo application. However, previously used stabilization of DNAzymes by site-specific phosphorothioate (PT) modifications reduces the catalytic activity, and the PTO displays toxic side effects when applied in vivo. Thus, improving the stability of DNAzymes without reducing their catalytic activity is essential if the potential of these compounds should be realized in vivo. RESULTS: The Circozyme was tested targeting the mRNA of the most common genetic rearrangement in pediatric acute lymphoblastic leukemia TEL/AML1 (ETV6/RUNX1). The Circozyme exhibits a stability comparable to PTO-modified DNAzymes without reduction of catalytic activity and specificity and may represent a promising tool for DNAzyme in vivo applications. CONCLUSION: The inclusion of the catalytic site and the specific mRNA binding sequence of the DNAzyme into a circular loop-stem-loop structure (Circozyme) of approximately 70 bases presented here represents a new effective possibility of DNAzyme stabilization.
Authors:
Georg Seifert; Tillmann Taube; Kriztina Paal; Hagen Graf von Einsiedel; Sven Wellmann; Günter Henze; Karl Seeger; Matthias Schroff; Burghardt Wittig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nucleosides, nucleotides & nucleic acids     Volume:  25     ISSN:  1525-7770     ISO Abbreviation:  Nucleosides Nucleotides Nucleic Acids     Publication Date:  2006  
Date Detail:
Created Date:  2006-08-10     Completed Date:  2006-09-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100892832     Medline TA:  Nucleosides Nucleotides Nucleic Acids     Country:  United States    
Other Details:
Languages:  eng     Pagination:  785-93     Citation Subset:  IM    
Affiliation:
Charité Universitätsmedizin Berlin, Otto-Heubner Center for Pediatric and Adolescent Medicine (OHC), Department of Pediatric Oncology/Hematology, Berlin, Germany.
Data Bank Information
Bank Name/Acc. No.:
RefSeq/NM_001987
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Catalysis
Core Binding Factor Alpha 2 Subunit / genetics*
DNA, Catalytic / chemistry*,  metabolism
DNA, Circular / chemistry*,  metabolism
Enzyme Stability
Molecular Sequence Data
Nucleic Acid Conformation
Oncogene Proteins, Fusion / genetics*
RNA, Messenger / chemistry*,  genetics*,  metabolism
Chemical
Reg. No./Substance:
0/Core Binding Factor Alpha 2 Subunit; 0/DNA, Catalytic; 0/DNA, Circular; 0/Oncogene Proteins, Fusion; 0/RNA, Messenger; 0/TEL-AML1 fusion protein

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