<i>Ex vivo</i>regulation of specific gene expression by nanomolar concentration of double-stranded dumbbell oligonucleotides

Clusel, Catherine; Ugarte, Edgardo; Enjolras, Nathalie; Vasseur, Marc; Blumenfeld, Marta

doi:10.1093/nar/21.15.3405

Cited by 62 publications

(40 citation statements)

References 39 publications

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“…Circular oligonucleotides have no ends and thus can be considerably more resistant to such degradation. 108,85,111 c. Cross-Linked Oligonucleotides: The clamp and circular oligonucleotide approaches are strategies in which two DNA-binding domains are linked at their end or ends. Another approach would be to link them across the center.…”

Section: A Clamp or Fold-back Oligonucleotidesmentioning

confidence: 99%

Preorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides

1997

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Section: A Clamp or Fold-back Oligonucleotidesmentioning

confidence: 99%

Preorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides

1997

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“…Several different structures of doublestranded DNA, including unmodified oligonucleotide duplexes, ab-anomeric oligonucleotides, phosphorothioate oligonucleotide duplexes and dumbbell oligonucleotides, have been introduced as decoys for transcription factors. [1][2][3][4][5][6][7][8] The main limitation of unmodified ODN is relatively easy degradation by nucleases prevalent in sera and cells. To rectify this problem, ODNs with modified linkages, such as phosphorothioate and methylphosphonate, were developed.…”

Section: Introductionmentioning

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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“…[56][57][58] A principal goal has been the use of such compounds as decoys to sequester proteins which cause a disease state (see structure 26 for a DNA example). In another example, RNA decoys such as 27 have been constructed for the binding of HIV-1 transactivating proteins.…”

Section: Circular Structures As Decoysmentioning

confidence: 99%

Recognition of DNA, RNA, and Proteins by Circular Oligonucleotides

Kool

1998

Acc. Chem. Res.

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IntroductionWhile the backbone organization of DNA and RNA is normally quite regular, there are many structural forms which these molecules can adapt by undergoing various secondary and tertiary helical and folded interactions, by being subjected to twisting and bending, and by interconversion between various topological and knotted variations. Probably the most common structural form of DNA in nature is a long double helix in which the ends are joined into a circle. The genomes of most lower organisms are organized in this way, 1 and clearly this circular structure lends some important advantage to these organisms or evolution would not have selected for it.Most chemists are chiefly interested in structure and reactivity of molecules smaller than entire bacterial genomes; such large circular DNAs will not be discussed herein for that reason. Of particular interest, then, is the question: what are the smallest cyclic DNAs or RNAs which exist in nature? For DNA, the answer appears to be several hundred to perhaps 1500 nucleotides (nt), which is still rather large. For RNA, probably the smallest known circular structures are the viroid RNAs, which are single-stranded and as small as 246 nucleotides in size. 2 However, this is far from the smallest possible cyclic nucleic acid structure. Duplex DNA can exist in circles at least as small as 125 bp (base pairs); 3 cyclic structures smaller than this are difficult to achieve because of the rigidity of the double helix. 4 Single-stranded DNA and RNAs do not have this problem, and rings as small as two nucleotides are known. 5 Thus, the realm of possible cyclic DNA and RNA structures falls easily into the size range most palatable to chemists.Interestingly, although small synthetic circular DNAs had been reported a number of times as early as in 1968, 6 prior to 1990 there were no reported studies investigating the effect of this quite significant structural modification on DNA's molecular recognition properties. Despite this, there was quite reasonable precedent that such a structural alteration might have a large effect on such recognition properties. Indeed, in recent decades it has become widely recognized that macrocyclic molecular structures can have strong advantages in the formation of noncovalent complexes. 7 Among these advantages (relative to noncyclic molecules of similar structure) are tighter binding affinity and greater specificity for binding the target of interest. The advent of simple synthetic approaches to the construction of oligonucleotides has led to an explosion of studies aimed at studying and modifying their noncovalent binding properties. In our early work we proposed that the principle of macrocyclic recognition could also be applied to nucleic acids in small synthetic well-defined systems. The testing of that hypothesis is the subject of this Account. Recognition of Nucleic AcidsIn 1990 when we began our studies it was not trivial to synthesize a circular oligonucleotide from a linear precursor; however, the development of new synthetic meth...

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Ex vivoregulation of specific gene expression by nanomolar concentration of double-stranded dumbbell oligonucleotides

Cited by 62 publications

References 39 publications

Preorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides

Preorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides

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

Recognition of DNA, RNA, and Proteins by Circular Oligonucleotides

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