ArticleNucleic acids research2004
Locked nucleic acid modified DNA enzymes targeting early growth response-1 inhibit human vascular smooth muscle cell growth.
Article in Nucleic acids research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 57 citations in OpenAlex.
- Influence of LNA modifications on the activity of the 10-23 DNAzyme.RSC advances · 2025Article
- Early growth response-1, a dynamic conduit in cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- A promising nucleic acid therapy drug: DNAzymes and its delivery system.Frontiers in molecular biosciences · 2023Review
- Specific DNAzymes cleave the 300-618 nt of 5'UTR to inhibit DHAV-1 translation and replication.Frontiers in microbiology · 2022Article
- EPAC in Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020Review
- Dual specificity phosphatase 15 regulates Erk activation in Schwann cells.Journal of neurochemistry · 2017Article
- DNA Catalysis: The Chemical Repertoire of DNAzymes.Molecules (Basel, Switzerland) · 2015Review
- Inhibition of Egr1 expression underlies the anti-mitogenic effects of cAMP in vascular smooth muscle cells.Journal of molecular and cellular cardiology · 2014Article
- Nucleoside triphosphates--building blocks for the modification of nucleic acids.Molecules (Basel, Switzerland) · 2012Review
- Deoxyribozymes and bioinformatics: complementary tools to investigate axon regeneration.Cell and tissue research · 2012Review
- Egr-1 expression during neointimal development in flow-associated pulmonary hypertension.The American journal of pathology · 2011Article
- Locked and unlocked nucleosides in functional nucleic acids.Molecules (Basel, Switzerland) · 2011Article
- Chemical synthesis of LNA-2-thiouridine and its influence on stability and selectivity of oligonucleotide binding to RNA.Biochemistry · 2009Article
- DNAzymes and cardiovascular disease.British journal of pharmacology · 2008Review
- Brothers in arms: DNA enzymes, short interfering RNA, and the emerging wave of small-molecule nucleic acid-based gene-silencing strategies.The American journal of pathology · 2007Review
- Efficient inhibition of HIV-1 expression by LNA modified antisense oligonucleotides and DNAzymes targeted to functionally selected binding sites.Retrovirology · 2007Article
- Locked nucleoside analogues expand the potential of DNAzymes to cleave structured RNA targets.BMC molecular biology · 2006Article
- Locked nucleic acid: high-affinity targeting of complementary RNA for RNomics.Handbook of experimental pharmacology · 2006Review
- Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- In vitro selection, characterization, and application of deoxyribozymes that cleave RNA.Nucleic acids research · 2005Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Smooth muscle cell (SMC) proliferation and migration are key processes that occur in the pathogenesis of atherosclerosis and post-angioplasty restenosis. In the present study, we designed locked nucleic acid (LNA)-modified DNAzymes targeting a specific region spanning the translational start site of human EGR-1, an immediate-early gene, wherein two of the nucleotides in each of the 9+9 hybridizing arms of the DNAzyme were substituted with LNA monomers. In vitro cleavage experiments revealed that the LNA- modified DNAzyme (LzF4) cleaved a 32P-labelled 388 nt EGR-1 transcript with greater efficacy than its native unmodified phosphodiester counterpart, DzF. The scrambled versions of these molecules, LzF4SCR and DzFSCR, did not display any ability to cleave the transcript. Western blot analysis revealed that both active molecules abrogated serum-inducible EGR-1 protein expression in primary human aortic SMCs and inhibited serum-inducible SMC proliferation in a dose-dependent and non-toxic manner. SMC proliferation was inhibited by >50% with LzF4 at concentrations as low as 20 nM, whereas inhibition by DzF at this concentration was not evident. Finally, LzF4 and DzF inhibited SMC regrowth from the wound edge after mechanical injury in vitro. In contrast, neither DzFSCR nor LzF4SCR had any influence on EGR-1 protein expression, SMC proliferation or regrowth. These findings provide the first functional demonstration of LNA-modified DNAzyme efficacy in a biological setting of any kind. These studies also demonstrate that LNA modification increases DNAzyme potency without necessarily compromising specificity.
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