Phosphorothioate oligodeoxynucleotides—anti-sense inhibitors of gene expression?

Stein, C. A.; Tonkinson, John L.; Yakubov, L. A.

doi:10.1016/0163-7258(91)90032-h

Cited by 136 publications

(80 citation statements)

References 68 publications

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“…30,31 To overcome these problems, we employed the HVJ-liposome technique to transfect E2F decoy ODN into the rat carotid artery. In this delivery system, exogenous molecules, such as plasmid DNA or ODN, are enveloped in a liposome comprising phospholipids and cholesterol.…”

Section: Novel E2f Decoy Oligodeoxynucleotides Jd Ahn Et Almentioning

confidence: 99%

Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia

Morishita

Kaneda

et al. 2002

Gene Ther

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The transcription factor, E2F, plays a critical role in the transactivation of several genes involved in cell cycle regulation. Previous studies showed that the transfection of cis element double-stranded decoy oligodeoxynucleotides (ODNs) corresponding to E2F binding sites inhibited the proliferation of vascular smooth muscle cells (VSMCs) and neointimal hyperplasia in injured vessels. We have developed a novel E2F decoy ODN with a circular dumbbell structure (CD-E2F) and compared its effects with those of the conventional phosphorothioated E2F decoy (PS-E2F) ODN. CD-E2F ODN was more stable than PS-E2F ODN, largely preserving its structural integrity after incubation in the presence of nucleases and sera. Moreover, CD-E2F ODN inhibited high glucose-and serum-induced transcriptional expression of cell cycle regulatory genes more strongly than PS-E2F ODN. Transfection of CD-E2F ODN resulted in more effective inhibition of VSMC proliferation in vitro and neointimal formation in vivo, compared with PS-E2F ODN. An approximately 40-50% lower dose of CD-E2F ODN than PS-E2F ODN was sufficient to attain similar effects. In conclusion, our results indicate that CD-E2F ODN may be a valuable tool in gene therapy protocols for inhibiting VSMC proliferation and studying transcriptional regulation.

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Section: Novel E2f Decoy Oligodeoxynucleotides Jd Ahn Et Almentioning

confidence: 99%

Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia

Morishita

Kaneda

et al. 2002

Gene Ther

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“…Antisense ODNs are short chains of deoxynucleic acids (ϳ20 nucleotides) targeted to a specific mRNA sequence (A 1 receptor in the present report) of complementary bases. One possible mechanism of action is blocking the translation of the targeted mRNA by the nucleotide bases of the antisense ODNs that form hydrogen bonds with the complementary nucleotide bases of the targeted mRNA (Stein and Cohen, 1988;Walder and Walder, 1988). Another possible mechanism of action of ODNs is functioning as a substrate (ODN:mRNA complex) for enzymatic degradation by RNase H (Walder and Walder, 1988;Wahlestedt, 1994).…”

Section: Adenosine a 1 Receptor Antisensementioning

confidence: 99%

A₁Receptor and Adenosinergic Homeostatic Regulation of Sleep-Wakefulness: Effects of Antisense to the A₁Receptor in the Cholinergic Basal Forebrain

2003

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“…[1][2][3] Initial antisense experiments employed "natural" phosphodiester backbone oligonucleotides (Fig. 1b) to inhibit gene expression, however, such oligonucleotides are susceptible to degradation by exo-and endonucleases that are ubiquitous in serum and in the intracellular milieu.…”

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confidence: 99%

Morpholino antisense oligomer targeting human midkine: Its application for cancer therapy

Takei

Kadomatsu

Yuasa

et al. 2004

Intl Journal of Cancer

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Overexpression of a heparin-binding growth factor, midkine (MK), has been observed in many malignancies, making it an attractive therapeutic target. We used morpholino antisense oligomers to downregulate human MK expression in human prostate (PC-3) and colon carcinoma (SW620) cells, and determined the practical advantages of this anticancer therapeutic. Morpholino antisense oligomers directed against MK caused a dramatic and sequence-specific decrease of the target protein level, resulting in the inhibition of growth and anchorage-independent growth of the transfected cells. Furthermore, MK morpholino antisense oligomers exhibited a significant anticancer effect in the PC-3-and SW620-xenograft models. In comparison with phosphorothioatemodified oligodeoxynucleotide, morpholino oligomers showed 2 major advantages, stability and non-toxicity. MALDI-TOF mass spectrometric analysis showed that morpholino antisense oligomers were completely stable in the presence of serum nuclease(s). Serological examinations demonstrated no toxicity of MK morpholino antisense oligomers. Our study indicates that inhibition of MK expression by morpholino antisense oligomer is a promising novel and safe therapeutic strategy for cancers.

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Phosphorothioate oligodeoxynucleotides—anti-sense inhibitors of gene expression?

Cited by 136 publications

References 68 publications

Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia

Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia

A₁Receptor and Adenosinergic Homeostatic Regulation of Sleep-Wakefulness: Effects of Antisense to the A₁Receptor in the Cholinergic Basal Forebrain

Morpholino antisense oligomer targeting human midkine: Its application for cancer therapy

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Phosphorothioate oligodeoxynucleotides—anti-sense inhibitors of gene expression?

Cited by 136 publications

References 68 publications

Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia

Novel E2F decoy oligodeoxynucleotides inhibit in vitro vascular smooth muscle cell proliferation and in vivo neointimal hyperplasia

A1Receptor and Adenosinergic Homeostatic Regulation of Sleep-Wakefulness: Effects of Antisense to the A1Receptor in the Cholinergic Basal Forebrain

Morpholino antisense oligomer targeting human midkine: Its application for cancer therapy

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Product

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A₁Receptor and Adenosinergic Homeostatic Regulation of Sleep-Wakefulness: Effects of Antisense to the A₁Receptor in the Cholinergic Basal Forebrain