Volume 5, Issue 2 (May 2017)                   Res Mol Med (RMM) 2017, 5(2): 28-33 | Back to browse issues page

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Ahmadi N A, Esmaeili A, Javadi Zarnaghi F. Bioinformatics Designing of 10-23 Deoxyribozyme against Coding Region of Beta-galactosidase Gene . Res Mol Med (RMM) 2017; 5 (2) :28-33
URL: http://rmm.mazums.ac.ir/article-1-240-en.html
1- Cellular and Molecular Biology Division; Department of Biology; Faculty of Sciences, University of Isfahan; Isfahan; Iran
2- Cellular and Molecular Biology Division; Department of Biology; Faculty of Sciences, University of Isfahan; Isfahan; Iran , aesmaeili@sci.ui.ac.ir
Abstract:   (12342 Views)
Background: Deoxyribozymes (Dzs) can play a role as gene expression inhibitors at mRNA level. Among Dzs, the 10-23 deoxyribozyme has significant potentials for treatment of diseases. Designed Dz includes a catalytic core made of 15 deoxyribonucleotides and two binding arms consisted of 6-12 nucleotides for site specific binding to target RNA and hydrolysis. The enzyme has characteristic features for cleavage of the RNA target between an unpaired purine (A, G) and a paired pyrimidine (C or U). In this study, 10-23 Dz is designed for the coding region of the α-peptide of a lacZ gene.
Material and Methods: The primary sequence of a plasmid with α-complementation ability was taken from addgene database. To confirm sequence validity, ExPASy was used to analyze related ORFs for the retrieved sequence. The ORF with identical sequence to α-peptide was selected in the reverse complement sequence. Subsequently, the secondary structure of the α-peptide was analyzed in DINAMelt web server and Mfold software. Then the intended target site was selected inside the coding region of the α-peptide. The Dzs sequence was designed for the target site with nucleotide binding arms.
Results and conclusion: The resulted Dz in this study can be used as a promising catalytic DNA inside bacterial cells for blue-white screening. Criteria such as biological stability and catalytic rate of such enzymes must be evaluated in vivo and in vitro.
Full-Text [PDF 675 kb]   (1761 Downloads)    
Type of Study: Research | Subject: Biostatistics
Published: 2017/09/5

1. Fokina AA, Stetsenko DA, François J-C. DNA enzymes as potential therapeutics: towards clinical application of 10-23 DNAzymes. Expert Opin Biol Ther. 2015; 15, 689-711. PMID: 25772532
2. Wang X, Zhang L, Ding N, Yang X, Zhang J, He J, et al. Identification and characterization of DNAzymes targeting DNA methyltransferase I for suppressing bladder cancer proliferation. Biochem Biophys Res Commun. 2015; 461(2):329-33. PMID: 25888794
3. Zhu J, Li Z, Yang Z, He J. Studies on the preferred uracil–adenine base pair at the cleavage site of 10-23 DNAzyme by functional group modifications on adenine. Bioorg Med Chem. 2015; 23(15):4256-63. PMID: 26145822
4. Fokina AA, Stetsenko DA, Francois JC. DNA enzymes as potential therapeutics: towards clinical application of 10-23 DNAzymes. Expert Opin Biol Ther. 2015; 15(5):689-711. PMID: 25772532
5. Krug N, Hohlfeld JM, Kirsten A-M, Kornmann O, Beeh KM, Kappeler D, et al. Allergen-Induced Asthmatic Responses Modified by a GATA3-Specific DNAzyme. N Engl J Med. 2015; 372(21):1987-95. PMID: 25981191
6. Hou Z, Meng JR, Zhao JR, Hu BQ, Liu J, Yan XJ, et al. Inhibition of beta-lactamase-mediated oxacillin resistance in Staphylococcus aureus by a deoxyribozyme. Acta Pharmacol Sin. 2007; 28(11):1775-182. PMID: 17959028
7. Hou Z, Meng JR, Niu C, Wang HF, Liu J, Hu BQ, et al. Restoration of antibiotic susceptibility in methicillin‐resistant staphylococcus aureus by targeting mecr1 with a phosphorothioate deoxyribozyme. Clin Exp Pharmacol Physiol. 2007; 34(11):1160-4. PMID: 17880371
8. Chen F, Li Z, Wang R, Liu B, Zeng Z, Zhang H, et al. Inhibition of ampicillin-resistant bacteria by novel mono-DNAzymes and di-DNAzyme targeted to β-lactamase mRNA. Oligonucleotides. 2004; 14(2):80-9. PMID: 15294072
9. Hou W, Ni Q, Wo J, Li M, Liu K, Chen L, et al. Inhibition of hepatitis B virus X gene expression by 10-23 DNAzymes. Antiviral Res. 2006; 72(3):190-6. PMID: 16930733
10. Unwalla H, Banerjea AC. Novel mono-and di-DNA-enzymes targeted to cleave TAT or TAT-REV RNA inhibit HIV-1 gene expression. Antiviral Res. 2001; 51(2):127-39. PMID: 11431037
11. Li J, Zhu D, Yi Z, He Y, Chun Y, Liu Y, et al. DNAzymes targeting the icl gene inhibit ICL expression and decrease Mycobacterium tuberculosis survival in macrophages. Oligonucleotides. 2005; 15(3):215-22. PMID: 16201909
12. Horwitz JP, Chua J, Curby RJ, Tomson AJ, Da Rooge MA, Fisher BE, et al. Substrates for Cytochemical Demonstration of Enzyme Activity. I. Some Substituted 3-Indolyl-β-D-glycopyranosides1a. J Med Chem. 1964; 7(4):574-5.
13. Langley KE, Villarejo MR, Fowler AV, Zamenhof PJ, Zabin I. Molecular basis of beta-galactosidase alpha-complementation. Proc Natl Acad Sci U S A. 1975; 72(4):1254-7. PMID: 1093175
14. Markham NR, Zuker M. DINAMelt web server for nucleic acid melting prediction. Nucleic Acids Res. 2005; 33(Web Server issue):W577-81. PMID: 15980540
15. Sun L-Q, Cairns MJ, Gerlach WL, Witherington C, Wang L, King A. Suppression of smooth muscle cell proliferation by a c-myc RNA-cleaving deoxyribozyme. J Biol Chem. 1999; 274(24):17236-41. PMID: 10358082
16. Abe H. [Nanostructured RNA for RNA interference]. Yakugaku Zasshi. 2013; 133(3):373-8. PMID: 23449417
17. Nakashima Y, Abe H, Abe N, Aikawa K, Ito Y. Branched RNA nanostructures for RNA interference. Chem Commun (Camb). 2011; 47(29):8367-9. PMID: 21691656 [DOI:10.1248/yakushi.12-00239-F]
18. Burnett JC, Rossi JJ. RNA-based therapeutics: current progress and future prospects. Chem Biol. 2012; 19(1):60-71. PMID: 22284355

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