Extremely high and specific activity of DNA enzymes in cells with a Philadelphia chromosome

Warashina, Masaki; Kuwabara, Tomoko; Nakamatsu, Yuka; Taira, Kazunari

doi:10.1016/s1074-5521(99)80039-8

Cited by 74 publications

(67 citation statements)

References 47 publications

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“…Fourth, a 9×9 DNAzyme directed to the AUG start codon of human c-Myc cleaved its target mRNA, blocked c-Myc expression, and inhibited proliferation of an arterial smooth muscle cell line (40). Finally, several DNAzymes targeting variants of bcr-abl mRNA inhibited reporter expression in HeLa cells (45), and suppressed protein expression and growth of CD34 + bone marrow cells from patients with chronic myeloid leukemia (46). 10-23 has recently been exploited in PCR-based strategies for the homogeneous amplification and quantification of nucleic acids in clinical specimens.…”

Section: Catalytic Dnasmentioning

confidence: 99%

Catalytic DNAs as potential therapeutic agents and sequence-specific molecular tools to dissect biological function

Khachigian¹

2000

J. Clin. Invest.

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Section: Catalytic Dnasmentioning

confidence: 99%

Catalytic DNAs as potential therapeutic agents and sequence-specific molecular tools to dissect biological function

Khachigian¹

2000

J. Clin. Invest.

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“…, respectively ( Figure 1D 16,26,27 These data, taken together, demonstrate sequence-, time-, and dose-dependent DNAzyme cleavage of human EGR-1 mRNA.…”

Section: Dnazymes Targeting Human Egr-1 Cleave In Vitro Transcribed Ementioning

confidence: 67%

Catalytic Oligodeoxynucleotides Define a Key Regulatory Role for Early Growth Response Factor-1 in the Porcine Model of Coronary In-Stent Restenosis

Lowe

Fahmy

Kavurma

et al. 2001

Circulation Research

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Abstract-Early growth response factor-1 (Egr-1) controls the expression of a growing number of genes involved in the pathogenesis of atherosclerosis and postangioplasty restenosis. Egr-1 is activated by diverse proatherogenic stimuli. As such, this transcription factor represents a key molecular target in efforts to control vascular lesion formation in humans.In this study, we have generated DNAzymes targeting specific sequences in human EGR-1 mRNA. These molecules cleave in vitro transcribed EGR-1 mRNA efficiently at preselected sites, inhibit EGR-1 protein expression in human aortic smooth muscle cells, block serum-inducible cell proliferation, and abrogate cellular regrowth after mechanical injury in vitro. These DNAzymes also selectively inhibit EGR-1 expression and proliferation of porcine arterial smooth muscle cells and reduce intimal thickening after stenting pig coronary arteries in vivo. Key Words: catalytic DNA Ⅲ transcription factors Ⅲ early growth response factor-1 Ⅲ stenting Ⅲ gene therapy T he capacity to selectively target specific mRNA sequences with catalytic molecules composed of DNA provides immense potential to broaden our understanding of the roles of specific mediators in normal and pathologic settings. Catalytic DNA can be used to cleave the phosphodiester linkage between virtually any unpaired purine and paired pyrimidine, selectivity being conferred by the nucleotide sequences of the hybridizing arms. These next-generation antisense oligonucleotides are extremely specific and easy to synthesize and have low toxicity, because they do not require phosphorothioate or other backbone modifications to confer nuclease resistance. DNAzyme biotechnology has practical therapeutic implications as a new category of genesuppression agents in pathophysiological settings.Stenting of coronary atherosclerotic lesions has revolutionized the treatment of cardiovascular disease in the last 5 years, after two landmark trials demonstrating a reduction in restenosis relative to coronary balloon angioplasty in comparable vessels.

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“…However, ribozymes result in only imperfect cleavage of target mRNAs (James and Gibson, 1998). New modifications to the antisense system, such as DNAzymes (Hamada et al, 1999;Kuwabara et al, 1998Kuwabara et al, , 2001aTanabe et al, 2000;Warashina et al, 1999), BCR/ABL junction-specific catalytic subunits of RNase P (Cobaleda and Sanchez-Garcia, 2000) or maxizymes; novel allosterically controllable ribozymes (Hamada et al, 1999;Kuwabara et al, 1998Kuwabara et al, , 2001aTanabe et al, 2000); may increase specificity and increase cleavage of BCR/ABL mRNA (Maran et al, 1998;Mendoza-Maldonado et al, 2002;Rowley et al, 1999).…”

Section: Antisense Strategiesmentioning

confidence: 99%

BCR/ABL: from molecular mechanisms of leukemia induction to treatment of chronic myelogenous leukemia

2002

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Extremely high and specific activity of DNA enzymes in cells with a Philadelphia chromosome

Abstract: DNA enzymes with 2'-O-methyl modifications are potentially useful as gene-inactivating agents in the treatment of diseases such as CML. In contrast to conventional antisense DNAs, some of the DNA enzymes used in this study were highly specific and cleaved only abnormal BCR-ABL mRNA.

Cited by 74 publications

References 47 publications

Catalytic DNAs as potential therapeutic agents and sequence-specific molecular tools to dissect biological function

Catalytic DNAs as potential therapeutic agents and sequence-specific molecular tools to dissect biological function

Catalytic Oligodeoxynucleotides Define a Key Regulatory Role for Early Growth Response Factor-1 in the Porcine Model of Coronary In-Stent Restenosis

BCR/ABL: from molecular mechanisms of leukemia induction to treatment of chronic myelogenous leukemia

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